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{{Infobox medical condition (new)
| name = Graves' disease
| synonyms = Toxic diffuse goiter, <br />Flajani–Basedow–Graves disease
| image = Proptosis and lid retraction from Graves' Disease.jpg
| caption = The classic finding of [[exophthalmos]] and lid retraction in Graves' disease
| field = [[Endocrinology]]
| symptoms = [[goitre|Enlarged thyroid]], [[irritability]], [[myopathy|muscle weakness]], [[insomnia|sleeping problems]], [[tachycardia|fast heartbeat]], [[weight loss]], [[heat intolerance|poor tolerance of heat]],<ref name=NIH2012/> [[anxiety]], tremor of hands or fingers, warm and moist skin, increased [[perspiration]], [[goiter]], changes in menstrual cycle, easy bruising, [[erectile dysfunction]], reduced libido, frequent bowel movements, bulging eyes ([[Graves' ophthalmopathy]]), thick red skin on shins or the top of foot ([[pretibial myxedema]])<ref name="AR">{{cite web |title=Graves' disease |url=https://www.autoimmuneregistry.org/graves-disease |access-date=15 June 2022 |website=Autoimmune Registry Inc.}}</ref>
| complications = [[Graves' ophthalmopathy]]<ref name=NIH2012/>
| onset =
| duration =
| causes = Unknown<ref name=Men2014/>
| risks = Family history, other [[autoimmune disease]]s<ref name=NIH2012/>
| diagnosis = Blood tests, [[radioiodine]] uptake<ref name=NIH2012/><ref name=NEJM2008/>
| differential =
| prevention =
| treatment = [[Radioiodine therapy]], [[antithyroid agents|antithyroid]] and [[beta blocker]] medications, [[thyroidectomy|thyroid surgery]]<ref name=NIH2012/>
| medication =
| prognosis =
| frequency = 0.5% (males), 3% (females)<ref name=Hen2015/>
| deaths =
}}
<!-- Definition and symptoms -->
'''Graves' disease''', also known as '''toxic diffuse goiter''' or '''Basedow’s disease''', is an [[autoimmune disease]] that affects the [[thyroid]].<ref name=NIH2012/> It frequently results in and is the most common cause of [[hyperthyroidism]].<ref name=Hen2015/> It also often results in an [[goitre|enlarged thyroid]].<ref name=NIH2012/> Signs and symptoms of hyperthyroidism may include [[irritability]], [[myopathy|muscle weakness]], [[insomnia|sleeping problems]], a [[tachycardia|fast heartbeat]], [[heat intolerance|poor tolerance of heat]], [[diarrhea]] and [[weight loss#unintentional|unintentional weight loss]].<ref name=NIH2012/> Other symptoms may include thickening of the skin on the shins, known as [[pretibial myxedema]], and [[exophthalmos|eye bulging]], a condition caused by [[Graves' ophthalmopathy]].<ref name=NIH2012/> About 25 to 30% of people with the condition develop eye problems.<ref name=NIH2012>{{cite web|title = Graves Disease|url = http://www.niddk.nih.gov/health-information/health-topics/endocrine/graves-disease/Pages/fact-sheet.aspx|website = www.niddk.nih.gov|access-date = 2015-04-02|date = August 10, 2012|url-status = dead|archive-url = https://web.archive.org/web/20150402223830/http://www.niddk.nih.gov/health-information/health-topics/endocrine/graves-disease/Pages/fact-sheet.aspx|archive-date = April 2, 2015}}</ref><ref name=NEJM2008/>
<!-- Cause -->The exact cause of the disease is unclear, but symptoms are a result of antibodies binding to receptors on the thyroid causing over-expression of thyroid hormone.<ref name=Men2014>{{cite journal | vauthors = Menconi F, Marcocci C, Marinò M | title = Diagnosis and classification of Graves disease | journal = Autoimmunity Reviews | volume = 13 | issue = 4–5 | pages = 398–402 | date = 2014 | pmid = 24424182 | doi = 10.1016/j.autrev.2014.01.013 }}</ref> Persons are more likely to be affected if they have a family member with the disease.<ref name=NIH2012/> If one [[identical twin|monozygotic twin]] is affected, a 30% chance exists that the other twin will also have the disease.<ref name=Nik2012/> The onset of disease may be triggered by physical or emotional stress, infection, or [[childbirth|giving birth]].<ref name=NEJM2008/> Those with other autoimmune diseases, such as [[type 1 diabetes]] and [[rheumatoid arthritis]], are more likely to be affected.<ref name=NIH2012/> Smoking increases the risk of disease and may worsen eye problems.<ref name=NIH2012/> The disorder results from an [[antibody]], called thyroid-stimulating immunoglobulin (TSI), that has a similar effect to [[thyroid stimulating hormone]] (TSH).<ref name=NIH2012/> These TSI antibodies cause the [[thyroid gland]] to produce excess [[thyroid hormones]].<ref name=NIH2012/> The diagnosis may be suspected based on symptoms and confirmed with blood tests and [[radioiodine]] uptake.<ref name=NIH2012/><ref name=NEJM2008>{{cite journal | vauthors = Brent GA | title = Clinical practice. Grave disease | journal = The New England Journal of Medicine | volume = 358 | issue = 24 | pages = 2594–605 | date = June 2008 | pmid = 18550875 | doi = 10.1056/NEJMcp0801880 }}</ref> Typically, blood tests show a raised [[triiodothyronine|T<sub>3</sub>]] and [[thyroxine|T<sub>4</sub>]], low TSH, increased radioiodine uptake in all areas of the thyroid, and TSI antibodies.<ref name=NEJM2008/>
<!-- Prevention and treatment -->
The three treatment options are [[radioiodine therapy]], medications, and [[thyroidectomy|thyroid surgery]].<ref name=NIH2012/> Radioiodine therapy involves taking [[iodine-131]] by mouth, which is then concentrated in the thyroid and destroys it over weeks to months.<ref name=NIH2012/> The resulting [[hypothyroidism]] is treated with [[thyroid hormone#Medical use|synthetic thyroid hormones]].<ref name=NIH2012/> Medications such as [[beta blockers]] may control some of the symptoms, and [[anti-thyroid medication|antithyroid medication]]s such as [[methimazole]] may temporarily help people, while other treatments are having effect.<ref name=NIH2012/> Surgery to remove the thyroid is another option.<ref name=NIH2012/> Eye problems may require additional treatments.<ref name=NIH2012/>
<!-- Epidemiology and history -->
Graves disease develops in about 0.5% of males and 3.0% of females.<ref name=Hen2015>{{cite journal | vauthors = Burch HB, Cooper DS | title = Management of Graves Disease: A Review | journal = JAMA | volume = 314 | issue = 23 | pages = 2544–54 | date = December 2015 | pmid = 26670972 | doi = 10.1001/jama.2015.16535 }}</ref> It occurs about 7.5 times more often in women than in men.<ref name=NIH2012/> Often, it starts between the ages of 40 and 60, but can begin at any age.<ref name=Nik2012/> It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).<ref name=NIH2012/><ref name=NEJM2008/> The condition is named after Irish surgeon [[Robert James Graves|Robert Graves]], who described it in 1835.<ref name=Nik2012/> A number of prior descriptions also exist.<ref name=Nik2012>{{cite book|last1=Nikiforov|first1=Yuri E.|last2=Biddinger|first2=Paul W.|last3=Nikiforova|first3=Lester D.R.|last4=Biddinger|first4=Paul W. | name-list-style = vanc |title=Diagnostic pathology and molecular genetics of the thyroid|date=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=9781451114553|page=69|edition=2nd|url=https://books.google.com/books?id=jX1h00B4QJoC&pg=PA69|url-status=live|archive-url=https://web.archive.org/web/20170908171950/https://books.google.com/books?id=jX1h00B4QJoC&pg=PA69|archive-date=2017-09-08}}</ref>
==Signs and symptoms==
{{Main|Signs and symptoms of Graves' disease}}
[[Image:HyperaldosteronismSymptoms.jpeg|thumb|upright=1.3|Graves disease symptoms]]
The signs and symptoms of Graves disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being [[Graves ophthalmopathy]], [[goiter]], and [[pretibial myxedema]] (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly [[insomnia]], hand [[tremor]], [[hyperactivity]], hair loss, excessive [[sweating]], [[oligomenorrhea]], itching, [[heat intolerance]], [[weight loss]] despite [[increased appetite]], [[diarrhea]], frequent [[defecation]], [[palpitation]]s, [[muscle weakness|periodic partial muscle weakness or paralysis]] in those especially of Asian descent,<ref>{{cite book|last1=N. Burrow|first1=Gerard|last2=H. Oppenheimer|first2=Jack|last3=Volpé|first3=Robert|name-list-style=vanc|title=Thyroid function & disease|date=1989|publisher=W.B. Saunders |isbn=0721621902|url-access=registration|url=https://archive.org/details/thyroidfunctiond00burr}}</ref> and skin warmth and moistness.<ref name=agabegi2nd157>page 157 in:{{cite book | first1 = Elizabeth D | last1 = Agabegi | last2 = Agabegi | first2 = Steven S. | name-list-style = vanc | title = Step-Up to Medicine (Step-Up Series) | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2008 | isbn = 978-0-7817-7153-5 | url-access = registration | url = https://archive.org/details/stepuptomedicine0000agab }}</ref> Further signs that may be seen on [[physical examination]] are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, [[lid lag]], excessive [[tears|lacrimation]] due to Graves' ophthalmopathy, [[Heart arrhythmia|arrhythmia]]s of the heart, such as [[sinus tachycardia]], [[atrial fibrillation]], and [[premature ventricular contraction]]s, and [[hypertension]].<ref name=agabegi2nd157/><ref>{{cite journal | vauthors = Bunevicius R, Prange AJ | title = Psychiatric manifestations of Graves hyperthyroidism: pathophysiology and treatment options | journal = CNS Drugs | volume = 20 | issue = 11 | pages = 897–909 | year = 2006 | pmid = 17044727 | doi = 10.2165/00023210-200620110-00003 | s2cid = 20003511 }}</ref>
==Cause==
The exact cause is unclear, but it is believed to involve a combination of genetic and environmental factors.<ref name=Men2014/> While a theoretical mechanism occurs by which exposure to severe stressors and high levels of subsequent distress such as [[post-traumatic stress disorder]] <!-- (PTSD) --> could increase the risk of immune disease and cause an aggravation of the autoimmune response that leads to Graves disease, more robust clinical data are needed for a firm conclusion.<ref>{{cite journal | vauthors = Falgarone G, Heshmati HM, Cohen R, Reach G | title = Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves' disease | journal = European Journal of Endocrinology | volume = 168 | issue = 1 | pages = R13-8 | date = January 2013 | pmid = 23027804 | doi = 10.1530/EJE-12-0539 | doi-access = free }}</ref>
===Genetics===
A [[genetics|genetic]] predisposition for Graves' disease is seen, with some people more prone to develop [[thyrotropin receptor|TSH receptor]]-activating antibodies due to a genetic cause. [[Human leukocyte antigen]] DR (especially DR3) appears to play a role.<ref name="EndocrReview1993">{{cite journal | vauthors = Tomer Y, Davies TF | title = Infection, thyroid disease, and autoimmunity | journal = Endocrine Reviews | volume = 14 | issue = 1 | pages = 107–20 | date = February 1993 | doi = 10.1210/edrv-14-1-107 | pmid = 8491150 }}</ref> To date, no clear genetic defect has been found to point to a [[Monogenic (genetics)|single-gene]] cause.{{citation needed|date=June 2022}}
Genes believed to be involved include those for [[thyroglobulin]], [[thyrotropin receptor]], [[protein tyrosine phosphatase]] nonreceptor type 22 (''[[PTPN22]]''), and [[cytotoxic T-lymphocyte–associated antigen 4]], among others.<ref name=NEJM2016>{{cite journal | vauthors = Smith TJ, Hegedüs L | title = Graves' Disease | journal = The New England Journal of Medicine | volume = 375 | issue = 16 | pages = 1552–1565 | date = October 2016 | pmid = 27797318 | doi = 10.1056/NEJMra1510030 | url = https://findresearcher.sdu.dk:8443/ws/files/128446579/Graves_Disease.pdf | access-date = 2020-05-29 | archive-date = 2020-08-01 | archive-url = https://web.archive.org/web/20200801093036/https://findresearcher.sdu.dk:8443/ws/files/128446579/Graves_Disease.pdf | url-status = dead }}</ref>
===Infectious trigger===
Since Graves disease is an autoimmune disease that appears suddenly, often later in life, a [[Virus|viral]] or [[bacteria]]l infection may trigger antibodies, which cross-react with the human TSH receptor, a phenomenon known as [[antigenic mimicry]].<ref>{{cite journal | vauthors = Desailloud R, Hober D | title = Viruses and thyroiditis: an update | journal = Virology Journal | volume = 6 | pages = 5 | date = January 2009 | pmid = 19138419 | pmc = 2654877 | doi = 10.1186/1743-422X-6-5 | doi-access = free }}</ref>
The bacterium ''[[Yersinia enterocolitica]]'' bears structural similarity with the human thyrotropin receptor<ref name="EndocrReview1993"/> and was hypothesized to contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals.<ref>{{cite journal | vauthors = Toivanen P, Toivanen A | title = Does Yersinia induce autoimmunity? | journal = International Archives of Allergy and Immunology | volume = 104 | issue = 2 | pages = 107–11 | year = 1994 | pmid = 8199453 | doi = 10.1159/000236717 }}</ref>
In the 1990s, ''Y. enterocolitica'' was suggested to be possibly [[Association (statistics)|associated]] with Graves' disease.<ref>{{cite journal | vauthors = Strieder TG, Wenzel BE, Prummel MF, Tijssen JG, Wiersinga WM | title = Increased prevalence of antibodies to enteropathogenic Yersinia enterocolitica virulence proteins in relatives of patients with autoimmune thyroid disease | journal = Clinical and Experimental Immunology | volume = 132 | issue = 2 | pages = 278–82 | date = May 2003 | pmid = 12699417 | pmc = 1808711 | doi = 10.1046/j.1365-2249.2003.02139.x }}</ref>
More recently, the role for ''Y. enterocolitica'' has been disputed.<ref>{{cite journal | vauthors = Hansen PS, Wenzel BE, Brix TH, Hegedüs L | title = Yersinia enterocolitica infection does not confer an increased risk of thyroid antibodies: evidence from a Danish twin study | journal = Clinical and Experimental Immunology | volume = 146 | issue = 1 | pages = 32–8 | date = October 2006 | pmid = 16968395 | pmc = 1809723 | doi = 10.1111/j.1365-2249.2006.03183.x }}</ref>
[[Epstein–Barr virus]] <!-- (EBV) --> is another potential trigger.<ref>{{cite book |last1=Moore |first1=Elaine A. |last2=Moore |first2=Lisa Marie | name-list-style = vanc |title=Advances in Graves' Disease and Other Hyperthyroid Disorders |date=2013 |publisher=McFarland |isbn=9780786471898 |page=77 |url=https://books.google.com/books?id=0YMoAQAAQBAJ&pg=PA77 |language=en}}</ref>
==Mechanism==
Thyroid-stimulating immunoglobulins recognize and bind to the TSH receptor, which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3). Thyroxine receptors in the pituitary gland are activated by the surplus hormone, suppressing additional release of TSH in a negative feedback loop. The result is very high levels of circulating thyroid hormones and a low TSH level.{{citation needed|date=July 2022}}
===Pathophysiology===
[[File:Histopathology of Graves' disease - medium mag.jpg|thumb|Histopathology of a case of Grave's disease. It shows marked hyperplasia of [[thyroid follicular cell]]s, generally more so than [[toxic multinodular goitre]], forming papillae into the thyroid follicles, and with scalloping of the peripheral colloid.]]
Graves' disease is an [[autoimmunity|autoimmune]] disorder, in which the body produces [[antibody|antibodies]] that are specific to a [[self-protein]] - the receptor for thyroid-stimulating hormone. (Antibodies to thyroglobulin and to the [[thyroid hormone]]s T3 and T4 may also be produced.)
These antibodies cause hyperthyroidism because they bind to the TSHr and [[chronic (medicine)|chronically]] stimulate it. The TSHr is expressed on the [[thyroid follicular cell]]s of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4. This, in turn, causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.
The infiltrative exophthalmos frequently encountered has been explained by postulating that the thyroid gland and the extraocular muscles share a common antigen, which is recognized by the antibodies. Antibodies binding to the extraocular muscles would cause swelling behind the eyeball.
The "orange peel" skin has been explained by the infiltration of antibodies under the skin, causing an inflammatory reaction and subsequent fibrous plaques.
'''The three types of autoantibodies to the TSH receptor are:'''
# '''Thyroid stimulating immunoglobulins:''' these antibodies (mainly IgG) act as long-acting thyroid stimulants, activating the cells through a slower and more drawn out process compared to TSH, leading to an elevated production of thyroid hormone.
# '''Thyroid growth immunoglobulins:''' these antibodies bind directly to the TSH receptor and have been implicated in the growth of thyroid follicles.
# '''Thyrotrophin binding-inhibiting immunoglobulins:''' these antibodies inhibit the normal union of TSH with its receptor.
#* Some actually act as if TSH itself is binding to its receptor, thus inducing thyroid function.
#* Other types may not stimulate the thyroid gland, but <u>prevent</u> TSI and TSH from binding to and stimulating the receptor.
Another effect of hyperthyroidism is bone loss from osteoporosis, caused by an increased excretion of calcium and phosphorus in the urine and stool. The effects can be minimized if the hyperthyroidism is treated early. [[Thyrotoxicosis]] can also augment calcium levels in the blood by as much as 25%. This can cause stomach upset, excessive urination, and impaired kidney function.<ref>{{cite web |url=http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |title=Thyroid Disease, Osteoporosis and Calcium – Womens Health and Medical Information on |publisher=Medicinenet.com |date=2006-12-07 |access-date=2013-02-27 |url-status=live |archive-url=https://web.archive.org/web/20130307133403/http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |archive-date=2013-03-07 }}</ref>
==Diagnosis==
Graves disease may present clinically with one or more of these characteristic signs:{{citation needed|date=June 2022}}
* Rapid heartbeat (80%)
* Diffuse palpable goiter with audible [[bruit]] (70%)
* Tremor (40%)
* [[Exophthalmos]] (protuberance of one or both eyes), periorbital edema (25%)
* Fatigue (70%), weight loss (60%) with increased appetite in young people and poor appetite in the elderly, and other symptoms of hyperthyroidism/[[thyrotoxicosis]]
* Heat intolerance (55%)
* Tremulousness (55%)
* Palpitations (50%)
Two signs are truly diagnostic of Graves' disease (i.e., not seen in other hyperthyroid conditions): exophthalmos and non-pitting edema ([[pretibial myxedema]]). Goiter is an enlarged thyroid gland and is of the diffuse type (i.e., spread throughout the gland). Diffuse goiter may be seen with other causes of hyperthyroidism, although Graves' disease is the most common cause of diffuse goiter. A large goiter will be visible to the naked eye, but a small one (mild enlargement of the gland) may be detectable only by physical examination. Occasionally, goiter is not clinically detectable, but may be seen only with [[computed tomography]] or [[ultrasound]] examination of the thyroid.{{citation needed|date=June 2022}} Another sign of Graves' disease is hyperthyroidism, that is, overproduction of the thyroid hormones T3 and T4. Normal thyroid levels are also seen, and occasionally also hypothyroidism, which may assist in causing goiter (though it is not the cause of the Graves' disease). Hyperthyroidism in Graves' disease is confirmed, as with any other cause of hyperthyroidism, by measuring elevated blood levels of free (unbound) T3 and T4.{{citation needed|date=June 2022}}
Other useful laboratory measurements in Graves disease include thyroid-stimulating hormone (TSH, usually undetectable in Graves disease due to [[negative feedback]] from the elevated T3 and T4), and protein-bound [[iodine]] (elevated). [[serology|Serologically]] detected thyroid-stimulating antibodies, radioactive iodine <!-- (RAI) --> uptake, or thyroid [[Doppler ultrasonography|ultrasound with Doppler]] all can independently confirm a diagnosis of Graves disease.
[[Biopsy]] to obtain histiological testing is not normally required, but may be obtained if thyroidectomy is performed.<!-- see eMedicine/med/topic929 of infobox -->
The goiter in Graves disease is often not nodular, but [[thyroid nodule]]s are also common.<ref name="pmid_9709909">{{cite journal | vauthors = Carnell NE, Valente WA | title = Thyroid nodules in Graves' disease: classification, characterization, and response to treatment | journal = Thyroid | volume = 8 | issue = 7 | pages = 571–6 | date = July 1998 | pmid = 9709909 | doi = 10.1089/thy.1998.8.571 }}</ref> Differentiating common forms of hyperthyroidism such as Graves' disease, single [[thyroid adenoma]], and [[toxic multinodular goiter]] is important to determine proper treatment.<ref name="pmid_9709909"/> The [[toxic multinodular goitre#Differentiation and terminology among types of goiter|differentiation among these entities has advanced]], as imaging and biochemical tests have improved. Measuring TSH-receptor antibodies with the h-TBII assay has been proven efficient and was the most practical approach found in one study.<ref name="pmid_15127319">{{cite journal | vauthors = Wallaschofski H, Kuwert T, Lohmann T | title = TSH-receptor autoantibodies - differentiation of hyperthyroidism between Graves' disease and toxic multinodular goitre | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 112 | issue = 4 | pages = 171–4 | date = April 2004 | pmid = 15127319 | doi = 10.1055/s-2004-817930 }}</ref>
===Eye disease===
{{Further|Graves ophthalmopathy|}}
Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease (TED), is the most common extrathyroidal manifestation of Graves' disease. It is a form of [[Idiopathic orbital inflammatory disease|idiopathic lymphocytic orbital inflammation]], and although its pathogenesis is not completely understood, autoimmune activation of orbital [[fibroblast]]s, which in TAO express the [[Thyrotropin receptor|TSH receptor]], is thought to play a central role.<ref>{{cite journal | vauthors = Shan SJ, Douglas RS | title = The pathophysiology of thyroid eye disease | journal = Journal of Neuro-Ophthalmology | volume = 34 | issue = 2 | pages = 177–85 | date = June 2014 | pmid = 24821101 | doi = 10.1097/wno.0000000000000132 | s2cid = 10998666 | doi-access = free }}</ref>
[[Hypertrophy]] of the extraocular muscles, [[adipogenesis]], and deposition of nonsulfated [[glycosaminoglycan]]s and hyaluronate, causes expansion of the orbital fat and muscle compartments, which within the confines of the bony orbit may lead to [[Optic neuropathy|dysthyroid optic neuropathy]], increased [[Glaucoma|intraocular pressures]], proptosis, venous congestion leading to chemosis and periorbital edema, and progressive remodeling of the orbital walls.<ref>{{cite journal | vauthors = Feldon SE, Muramatsu S, Weiner JM | title = Clinical classification of Graves' ophthalmopathy. Identification of risk factors for optic neuropathy | journal = Archives of Ophthalmology | volume = 102 | issue = 10 | pages = 1469–72 | date = October 1984 | pmid = 6548373 | doi = 10.1001/archopht.1984.01040031189015 }}</ref><ref>{{cite journal | vauthors = Gorman CA | title = The measurement of change in Graves' ophthalmopathy | journal = Thyroid | volume = 8 | issue = 6 | pages = 539–43 | date = June 1998 | pmid = 9669294 | doi = 10.1089/thy.1998.8.539 }}</ref><ref>{{cite journal | vauthors = Tan NY, Leong YY, Lang SS, Htoon ZM, Young SM, Sundar G | title = Radiologic Parameters of Orbital Bone Remodeling in Thyroid Eye Disease | journal = Investigative Ophthalmology & Visual Science | volume = 58 | issue = 5 | pages = 2527–2533 | date = May 2017 | pmid = 28492870 | doi = 10.1167/iovs.16-21035 | doi-access = free }}</ref> Other distinctive features of TAO include lid retraction, restrictive myopathy, superior limbic keratoconjunctivitis, and [[exposure keratopathy]].{{citation needed|date=June 2022}}
Severity of eye disease may be classified by the mnemonic: "NO SPECS":<ref name="pmid15310608">{{cite journal | vauthors = Cawood T, Moriarty P, O'Shea D | title = Recent developments in thyroid eye disease | journal = BMJ | volume = 329 | issue = 7462 | pages = 385–90 | date = August 2004 | pmid = 15310608 | pmc = 509348 | doi = 10.1136/bmj.329.7462.385 }}</ref>
* Class 0: No signs or symptoms
* Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)
* Class 2: Soft tissue involvement ([[oedema]] of [[conjunctiva]]e and lids, conjunctival injection, etc.)
* Class 3: [[Proptosis]]
* Class 4: [[Extraocular muscle]] involvement (usually with [[diplopia]])
* Class 5: Corneal involvement (primarily due to [[lagophthalmos]])
* Class 6: Sight loss (due to optic nerve involvement)
Typically, the natural history of TAO follows Rundle's curve, which describes a rapid worsening during an initial phase, up to a peak of maximum severity, and then improvement to a static plateau without, however, resolving back to a normal condition.<ref>{{cite journal | vauthors = Bartley GB | title = Rundle and his curve | journal = Archives of Ophthalmology | volume = 129 | issue = 3 | pages = 356–8 | date = March 2011 | pmid = 21402995 | doi = 10.1001/archophthalmol.2011.29 | doi-access = }}</ref>
==Management==
Treatment of Graves disease includes [[antithyroid agents|antithyroid drugs]] that reduce the production of thyroid hormone, [[radioiodine]] (radioactive iodine [[I-131]]) and [[thyroidectomy]] (surgical excision of the gland). As operating on a hyperthyroid patient is dangerous, prior to thyroidectomy, preoperative treatment with antithyroid drugs is given to render the patient euthyroid. Each of these treatments has advantages and disadvantages, and no single treatment approach is considered the best for everyone.{{citation needed|date=June 2022}}
Treatment with antithyroid medications must be administered for six months to two years to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. The risk of recurrence is about 40–50%, and lifelong treatment with antithyroid drugs carries some side effects such as [[agranulocytosis]] and [[liver disease]].<ref name=":0">{{cite journal | vauthors = Stathopoulos P, Gangidi S, Kotrotsos G, Cunliffe D | title = Graves' disease: a review of surgical indications, management, and complications in a cohort of 59 patients | journal = International Journal of Oral and Maxillofacial Surgery | volume = 44 | issue = 6 | pages = 713–7 | date = June 2015 | pmid = 25726089 | doi = 10.1016/j.ijom.2015.02.007 }}</ref> Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells. Therapy with radioiodine is the most common treatment in the United States, while antithyroid drugs and/or thyroidectomy are used more often in Europe, Japan, and most of the rest of the world.
[[beta blocker|β-Blockers]] (such as [[propranolol]]) may be used to inhibit the [[sympathetic nervous system]] symptoms of [[tachycardia]] and nausea until antithyroid treatments start to take effect. Pure β-blockers do not inhibit lid retraction in the eyes, which is mediated by alpha adrenergic receptors.
===Antithyroid drugs===
The main antithyroid drugs are [[carbimazole]] (in the UK), [[methimazole]] (in the US), and [[propylthiouracil]]/PTU. These drugs block the binding of iodine and coupling of iodotyrosines. The most dangerous side effect is agranulocytosis (1/250, more in PTU). Others include [[neutropenia|granulocytopenia]] (dose-dependent, which improves on cessation of the drug) and [[aplastic anemia]]. Patients on these medications should see a doctor if they develop sore throat or fever. The most common side effects are rash and [[Peripheral neuropathy|peripheral neuritis]]. These drugs also cross the [[placenta]] and are secreted in breast milk. [[Lugol's iodine]] may be used to block hormone synthesis before surgery.{{citation needed|date=June 2022}}
A [[randomized control trial]] testing single-dose treatment for Graves found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).<ref name="pmid11298092">{{cite journal | vauthors = Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A | title = Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism | journal = Clinical Endocrinology | volume = 54 | issue = 3 | pages = 385–90 | date = March 2001 | pmid = 11298092 | doi = 10.1046/j.1365-2265.2001.01239.x | s2cid = 24463399 }}</ref>
No difference in outcome was shown for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are a positive [[Thyrotropin receptor|TSHr]] [[antibody]] (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% ([[sensitivity and specificity|sensitivity]] 39%, [[sensitivity and specificity|specificity]] 98%), and a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.<ref name="pmid11331213">{{cite journal | vauthors = Glinoer D, de Nayer P, Bex M | title = Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study | journal = European Journal of Endocrinology | volume = 144 | issue = 5 | pages = 475–83 | date = May 2001 | pmid = 11331213 | doi = 10.1530/eje.0.1440475 | doi-access = free }}</ref>
===Radioiodine===
[[Image:Basedow-vor-nach-RIT.jpg|thumb|Scan of affected thyroid before (''top'') and after (''bottom'') [[radioiodine]] therapy]]
Radioiodine (radioactive iodine-131) was developed in the early 1940s at the [[Mallinckrodt General Clinical Research Center]]. This modality is suitable for most patients, although some prefer to use it mainly for older patients. Indications for radioiodine are failed medical therapy or surgery and where medical or surgical therapy are contraindicated. Hypothyroidism may be a complication of this therapy, but may be treated with thyroid hormones if it appears. The rationale for radioactive iodine is that it accumulates in the thyroid and irradiates the gland with its beta and gamma radiations, about 90% of the total radiation being emitted by the beta (electron) particles. The most common method of iodine-131 treatment is to administer a specified amount in microcuries per gram of thyroid gland based on palpation or radiodiagnostic imaging of the gland over 24 hours.<ref>{{cite book|last=Saha|first=Gopal B. | name-list-style = vanc |title=Fundamentals of Nuclear Pharmacy|edition=5|year=2009|publisher=Springer-Verlag New York, LLC|isbn=978-0387403601|page=342}}</ref> Patients who receive the therapy must be monitored regularly with thyroid blood tests to ensure they are treated with thyroid hormone before they become symptomatically hypothyroid.<ref>{{cite journal | vauthors = Schäffler A | title = Hormone replacement after thyroid and parathyroid surgery | journal = Deutsches Ärzteblatt International | volume = 107 | issue = 47 | pages = 827–34 | date = November 2010 | pmid = 21173898 | pmc = 3003466 | doi = 10.3238/arztebl.2010.0827 }}</ref>
Contraindications to RAI are [[pregnancy]] (absolute), ophthalmopathy (relative; it can aggravate thyroid eye disease), or solitary [[thyroid nodule|nodules]].<ref name="btf-thyroid.org">{{cite web |url=http://www.btf-thyroid.org/information/leaflets/39-radioactive-iodine-guide |title=Treatment of an Over-active or Enlarged Thyroid Gland with Radioactive Iodine – British Thyroid Foundation |website=Btf-thyroid.org |access-date=2016-09-10 |url-status=live |archive-url=https://web.archive.org/web/20160902004052/http://www.btf-thyroid.org/information/leaflets/39-radioactive-iodine-guide |archive-date=2016-09-02 }}</ref>
Disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring eventual thyroid hormone supplementation in the form of a daily pill(s). The radioiodine treatment acts slowly (over months to years) to destroy the thyroid gland, and Graves' disease–associated hyperthyroidism is not cured in all persons by radioiodine, but has a relapse rate that depends on the dose of radioiodine which is administered.<ref name="btf-thyroid.org"/> In rare cases, [[Radiation-induced thyroiditis|radiation induced thyroiditis]] has been linked to this treatment.<ref>{{Cite journal|last1=Mizokami|first1=Tetsuya|last2=Hamada|first2=Katsuhiko|last3=Maruta|first3=Tetsushi|last4=Higashi|first4=Kiichiro|last5=Tajiri|first5=Junichi|date=September 2016|title=Painful Radiation Thyroiditis after 131I Therapy for Graves' Hyperthyroidism: Clinical Features and Ultrasonographic Findings in Five Cases|journal=European Thyroid Journal|volume=5|issue=3|pages=201–206|doi=10.1159/000448398|issn=2235-0640|pmc=5091234|pmid=27843811}}</ref>
===Surgery===
{{Further|Thyroidectomy|}}
This modality is suitable for young people and pregnant females. Indications for thyroidectomy can be separated into absolute indications or relative indications. These indications aid in deciding which people would benefit most from surgery.<ref name=":0" /> The absolute indications are a large goiter (especially when compressing the [[vertebrate trachea|trachea]]), suspicious nodules or suspected [[cancer]] (to pathologically examine the thyroid), and people with ophthalmopathy and additionally if it is the person's preferred method of treatment or if refusing to undergo radioactive iodine treatment. Pregnancy is advised to be delayed for six months after radioactive iodine treatment.<ref name=":0" />
Both bilateral subtotal [[thyroidectomy]] and the Hartley-Dunhill procedure (hemithyroidectomy on one side and partial lobectomy on other side) are possible.
Advantages are immediate cure and potential removal of [[carcinoma]]. Its risks are injury of the [[recurrent laryngeal nerve]], [[hypoparathyroidism]] (due to removal of the [[parathyroid gland]]s), [[hematoma]] (which can be life-threatening if it compresses the trachea), relapse following medical treatment, infections (less common), and [[scarring]].<ref name=":0" /> The increase in the risk of nerve injury can be due to the increased vascularity of the thyroid parenchyma and the development of links between the thyroid capsule and the surrounding tissues. Reportedly, a 1% incidence exists of permanent [[Vocal fold paresis|recurrent laryngeal nerve paralysis]] after complete thyroidectomy.<ref name=":0" /> Risks related to anesthesia are many, thus coordination with the anesthesiologist and patient optimization for surgery preoperatively are essential. Removal of the gland enables complete biopsy to be performed to have definite evidence of cancer anywhere in the thyroid. (Needle biopsies are not so accurate at predicting a benign state of the thyroid). No further treatment of the thyroid is required, unless cancer is detected. Radioiodine uptake study may be done after surgery, to ensure all remaining (potentially cancerous) thyroid cells (i.e., near the nerves to the vocal cords) are destroyed. Besides this, the only remaining treatment will be [[levothyroxine]], or thyroid replacement pills to be taken for the rest of the patient's life.
A 2013 review article concludes that surgery appears to be the most successful in the management of Graves' disease, with total thyroidectomy being the preferred surgical option.<ref>{{cite journal | vauthors = Genovese BM, Noureldine SI, Gleeson EM, Tufano RP, Kandil E | title = What is the best definitive treatment for Graves' disease? A systematic review of the existing literature | journal = Annals of Surgical Oncology | volume = 20 | issue = 2 | pages = 660–7 | date = February 2013 | pmid = 22956065 | doi = 10.1245/s10434-012-2606-x | s2cid = 24759725 | type = review }}</ref>
===Eyes===
Mild cases are treated with lubricant eye drops or nonsteroidal anti-inflammatory drops. Severe cases threatening vision (corneal exposure or optic nerve compression) are treated with steroids or orbital decompression. In all cases, cessation of smoking is essential. Double vision can be corrected with prism glasses and surgery (the latter only when the process has been stable for a while).
Difficulty closing eyes can be treated with lubricant gel at night, or with tape on the eyes to enable full, deep sleep.
Orbital decompression can be performed to enable bulging eyes to retreat back into the head. Bone is removed from the skull behind the eyes, and space is made for the muscles and fatty tissue to fall back into the skull. <ref>{{Cite journal |last1=Limongi |first1=Roberto Murillo |last2=Feijó |first2=Eduardo Damous |last3=Rodrigues Lopes E Silva |first3=Marlos |last4=Akaishi |first4=Patrícia |last5=Velasco E Cruz |first5=Antônio Augusto |last6=Christian Pieroni-Gonçalves |first6=Allan |last7=Pereira |first7=Filipe |last8=Devoto |first8=Martin |last9=Bernardini |first9=Francesco |last10=Marques |first10=Victor |last11=Tao |first11=Jeremiah P. |date=February 2020 |title=Orbital Bone Decompression for Non-Thyroid Eye Disease Proptosis |url=https://pubmed.ncbi.nlm.nih.gov/31373985/ |journal=Ophthalmic Plastic and Reconstructive Surgery |volume=36 |issue=1 |pages=13–16 |doi=10.1097/IOP.0000000000001435 |issn=1537-2677 |pmid=31373985|s2cid=199388425 }}</ref>
For management of clinically active Graves disease, orbitopathy (clinical activity score >2) with at least mild to moderate severity, intravenous glucocorticoids are the treatment of choice, usually administered in the form of pulse intravenous methylprednisolone. Studies have consistently shown that pulse intravenous methylprednisolone is superior to oral glucocorticoids both in terms of efficacy and decreased side effects for managing Graves' orbitopathy.<ref>{{cite journal | vauthors = Roy A, Dutta D, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, Chowdhury S | title = Efficacy and safety of low dose oral prednisolone as compared to pulse intravenous methylprednisolone in managing moderate severe Graves' orbitopathy: A randomized controlled trial | journal = Indian Journal of Endocrinology and Metabolism | volume = 19 | issue = 3 | pages = 351–8 | date = 2015 | pmid = 25932389 | pmc = 4366772 | doi = 10.4103/2230-8210.152770 | doi-access = free }}</ref>
==Prognosis==
If left untreated, more serious [[complications (medical)|complications]] could result, including [[birth defect]]s in pregnancy, increased risk of a [[miscarriage]], bone mineral loss<ref name=Ken2001/> and, in extreme cases, death (e.g. indirectly through complications, or through a [[thyroid storm]] event). Graves' disease is often accompanied by an increase in heart rate, which may lead to further heart complications, including loss of the normal heart rhythm (atrial fibrillation), which may lead to stroke. If the eyes are proptotic (bulging) enough that the lids do not close completely at night, dryness will occur – with the risk of a secondary corneal infection, which could lead to blindness. Pressure on the optic nerve behind the globe can lead to visual field defects and vision loss, as well. Prolonged untreated hyperthyroidism can lead to bone loss, which may resolve when treated.<ref name="Ken2001">{{Cite book |url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA636 |title=Principles and practice of endocrinology and metabolism |date=2001 |publisher=Lippincott, Williams & Wilkins |isbn=978-0-7817-1750-2 |editor-last=Becker |editor-first=Kenneth L. |edition=3 |location=Philadelphia, Pa. |page=636 |archive-url=https://web.archive.org/web/20170908171950/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA636 |archive-date=2017-09-08 |url-status=live}}</ref>
==Epidemiology==
[[File:Causes of hyperthyroidism.png|thumb|Most common causes of [[hyperthyroidism]] by age<ref>{{cite journal|last1=Carlé|first1=Allan|last2=Pedersen|first2=Inge Bülow|last3=Knudsen|first3=Nils|last4=Perrild|first4=Hans|last5=Ovesen|first5=Lars|last6=Rasmussen|first6=Lone Banke|last7=Laurberg|first7=Peter|title=Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study|journal=European Journal of Endocrinology|volume=164|issue=5|year=2011|pages=801–809|issn=0804-4643|doi=10.1530/EJE-10-1155|pmid=21357288|doi-access=free}}</ref>]]
Graves' disease occurs in about 0.5% of people.<ref name=NEJM2008/> Graves' disease data has shown that the lifetime risk for women is around 3% and 0.5% for men.<ref>{{Citation|last1=Pokhrel|first1=Binod|title=Graves Disease|date=2020|url=http://www.ncbi.nlm.nih.gov/books/NBK448195/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=28846288|access-date=2020-12-04|last2=Bhusal|first2=Kamal}}</ref> It occurs about 7.5 times more often in women than in men<ref name=NIH2012/> and often starts between the ages of 40 and 60.<ref name=Nik2012/> It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).<ref name=NIH2012/><ref name=NEJM2008/>
==History==
Graves disease owes its name to the [[Anglo-Irish]] doctor [[Robert James Graves]],<ref>{{WhoNamedIt|doctor|695|Mathew Graves}}</ref> who described a case of goiter with exophthalmos in 1835.<ref>Graves, RJ. [https://archive.org/details/p2londonmedicals07londuoft ''Newly observed affection of the thyroid gland in females''] {{webarchive|url= https://web.archive.org/web/20160331121345/https://archive.org/details/p2londonmedicals07londuoft |date= 2016-03-31 }}. (Clinical lectures.) London Medical and Surgical Journal (Renshaw), 1835; 7 (part 2): 516–517. Reprinted in Medical Classics, 1940;5:33–36.</ref> ([[Medical eponyms]] are often styled nonpossessively; thus ''Graves' disease'' and ''Graves disease'' are variant stylings of the same term.)
The German [[Karl Adolph von Basedow]] independently reported the same constellation of symptoms in 1840.<ref>Von Basedow, KA. ''Exophthalmus durch Hypertrophie des Zellgewebes in der Augenhöhle''. ''[Casper's] Wochenschrift für die gesammte Heilkunde'', Berlin, 1840, 6: 197–204; 220–228. Partial English translation in: Ralph Hermon Major (1884–1970): ''Classic Descriptions of Disease''. Springfield, C. C. Thomas, 1932. 2nd edition, 1939; 3rd edition, 1945.</ref><ref>Von Basedow, KA. "Die Glotzaugen". ''[Casper's] Wochenschrift für die gesammte Heilkunde'', Berlin, 1848: 769–777.</ref> As a result, on the European continent, the terms "Basedow syndrome",<ref name="WNI" /> "Basedow disease", or "Morbus Basedow"<ref name="TMHP">{{cite-TMHP|Exophthalmic goiter, Basedow disease, Grave disesase}}, pages 82, 294, and 295.</ref> are more common than "Graves' disease".<ref name="WNI">{{WhoNamedIt|synd|1517|Basedow syndrome or disease}} – the history and naming of the disease</ref><ref>{{eMedicine|med|917|Goiter, Diffuse Toxic}}</ref>
Graves disease<ref name=WNI/><ref name=TMHP/> has also been called ''exophthalmic goiter''.<ref name=TMHP/>
Less commonly, it has been known as Parry disease,<ref name=WNI/><ref name=TMHP/> Begbie disease, Flajan disease, Flajani–Basedow syndrome, and Marsh disease.<ref name=WNI/> These names for the disease were derived from [[Caleb Hillier Parry]], [[James Begbie]], [[Giuseppe Flajani]], and [[Sir Henry Marsh| Henry Marsh]].<ref name=WNI/> Early reports, not widely circulated, of cases of goiter with exophthalmos were published by the Italians Giuseppe Flajani<ref>Flajani, G. ''Sopra un tumor freddo nell'anterior parte del collo broncocele. (Osservazione LXVII)''. In Collezione d'osservazioni e reflessioni di chirurgia. Rome, Michele A Ripa Presso Lino Contedini, 1802;3:270–273.</ref> and Antonio Giuseppe Testa,<ref>Testa, AG. ''Delle malattie del cuore, loro cagioni, specie, segni e cura.'' Bologna, 1810. 2nd edition in 3 volumes, Florence, 1823; Milano 1831; German translation, Halle, 1813.</ref> in 1802 and 1810, respectively.<ref>{{WhoNamedIt|doctor|1471|Giuseppe Flajani}}</ref> Prior to these, Caleb Hillier Parry,<ref>{{cite book | vauthors = Parry CH | chapter = Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart | title = Collections from the unpublished medical writings of C. H. Parry | location = London | date = 1825 | pages = 111–129 | quote = According to Garrison, Parry first noted the condition in 1786. He briefly reported it in his ''Elements of Pathology and Therapeutics'', 1815. Reprinted in Medical Classics, 1940, 5: 8–30 }}</ref> a notable provincial physician in England of the late 18th century (and a friend of [[Edward Miller-Gallus]]),<ref>{{cite journal | vauthors = Hull G | title = Caleb Hillier Parry 1755-1822: a notable provincial physician | journal = Journal of the Royal Society of Medicine | volume = 91 | issue = 6 | pages = 335–8 | date = June 1998 | pmid = 9771526 | pmc = 1296785 | doi = 10.1177/014107689809100618 }}</ref> described a case in 1786. This case was not published until 1825 - ten years ahead of Graves.<ref>{{WhoNamedIt|doctor|397|Caleb Hillier Parry}}</ref>
However, fair credit for the first description of Graves disease goes to the 12th-century [[Islamic medicine |Persian physician]] [[Zayn al-Din al-Jurjani|Sayyid Ismail al-Jurjani]],<ref>Sayyid Ismail Al-Jurjani. ''Thesaurus of the Shah of Khwarazm''.</ref> who noted the association of goiter and exophthalmos in his [[Zayn al-Din al-Jurjani#Thesaurus of the Shah of Khwarazm|''Thesaurus of the Shah of Khwarazm'']], the major medical dictionary of its time.<ref name=WNI/><ref>{{cite journal | vauthors = Ljunggren JG | title = [Who was the man behind the syndrome: Ismail al-Jurjani, Testa, Flagani, Parry, Graves or Basedow? Use the term hyperthyreosis instead] | journal = Läkartidningen | volume = 80 | issue = 32–33 | pages = 2902 | date = August 1983 | pmid = 6355710 }}</ref>
==Society and culture==
=== Notable cases ===
<!-- NB! - alphabetical order by surname, and please don't add very obscure persons -->
[[File:Marty Feldman.png|thumb|upright=1.3|[[Marty Feldman]] used his bulging eyes, caused by Graves' disease, for comedic effect.]]
* [[Ayaka]], Japanese singer, was diagnosed with Graves disease in 2007. After going public with her diagnosis in 2009, she took a two-year hiatus from music to focus on treatment.<ref>{{cite web |title=水嶋ヒロ・絢香、2ショット会見で結婚報告 絢香はバセドウ病を告白、年内で休業へ |url=http://beauty.oricon.co.jp/trend-culture/trend/news/64835/full/ |publisher=[[Oricon]] |language=ja |date=April 3, 2009 |access-date=November 19, 2015 |url-status=live |archive-url=https://web.archive.org/web/20151208132540/http://beauty.oricon.co.jp/trend-culture/trend/news/64835/full/ |archive-date=December 8, 2015 }}</ref><ref>{{cite web |title=絢香、初のセルフ・プロデュース・アルバムが発売決定！ |url=http://www.cdjournal.com/main/news/ayaka/41818 |publisher=CDJournal |language=ja |date=December 1, 2011 |access-date=November 19, 2015 |url-status=live |archive-url=https://web.archive.org/web/20151015101029/http://www.cdjournal.com/main/news/ayaka/41818 |archive-date=October 15, 2015 }}</ref>
* [[Susan Blow|Susan Elizabeth Blow]], American educator and founder of the first publicly funded kindergarten in the United States, was forced to retire and seek treatment for Graves disease in 1884.<ref>{{Cite book|title=Movers and Shakers, Scalawags and Suffragettes: Tales from Bellefontaine Cemetery|last=Shepley|first=Carol Ferring|publisher=Missouri History Museum|year=2008|location=St. Louis, Missouri}}</ref>
* [[George H. W. Bush]], former U.S. president, developed new [[atrial fibrillation]] and was diagnosed in 1991 with [[hyperthyroidism]] due to the disease and treated with radioactive iodine.<ref>{{cite news|last1=Okie|first1=Susan|date=May 10, 1991|title=Bush's Thyroid Condition Diagnosed As Graves' Disease|newspaper=[[The Washington Post]]|url=https://www.washingtonpost.com/archive/politics/1991/05/10/bushs-thyroid-condition-diagnosed-as-graves-disease/d3c91174-dec2-4f01-a191-ba3e81e48e69/|url-status=live|url-access=|access-date=June 17, 2023|archive-url=https://web.archive.org/web/20180107181333/https://www.washingtonpost.com/archive/politics/1991/05/10/bushs-thyroid-condition-diagnosed-as-graves-disease/d3c91174-dec2-4f01-a191-ba3e81e48e69/|archive-date=January 7, 2018}}</ref> The president's wife, [[Barbara Bush]], also developed the disease around the same time, which, in her case, produced severe infiltrative [[exophthalmos]].<ref>{{cite news| first = Lawrence K. | last = Altman | name-list-style = vanc | url = https://www.nytimes.com/1991/05/28/science/the-doctor-s-world-a-white-house-puzzle-immunity-ailments.html |title=The Doctor's World — A White House Puzzle: Immunity Ailments-Science Section|work=[[The New York Times]]|date=1991-05-28|access-date=2013-02-27|url-status=live|archive-url=https://web.archive.org/web/20130508015248/http://www.nytimes.com/1991/05/28/science/the-doctor-s-world-a-white-house-puzzle-immunity-ailments.html|archive-date=2013-05-08}}</ref>
* [[Rodney Dangerfield]], American comedian and actor<ref>{{cite web |url=http://www.pathologyoutlines.com/topic/thyroidgraves.html |title=Thyroid gland – Hyperplasia / goiter – Graves disease | first = Shahidul | last = Islam | name-list-style = vanc |website=Pathologyoutlines.com |date=2017-01-23 |access-date=2017-01-25 |url-status=live |archive-url=https://web.archive.org/web/20161214044717/http://pathologyoutlines.com/topic/thyroidgraves.html |archive-date=2016-12-14 }}</ref>
* [[Gail Devers]], American sprinter: A doctor considered amputating her feet after she developed blistering and swelling following radiation treatment for Graves' disease, but she went on to recover and win Olympic medals.
* [[Missy Elliott]], American hip-hop artist<ref>{{cite web|last=Oldenburg |first=Ann | name-list-style = vanc |url=http://content.usatoday.com/communities/entertainment/post/2011/06/missy-elliott-reveals-graves-disease-battle/1 |title=Update: Missy Elliott 'completely managing' Graves' disease |date=2011-06-24 |work=USA Today |publisher=Gannett}}</ref>
* [[Marty Feldman]], British comedy writer, comedian and actor<ref>{{Cite news|url=https://healthresearchfunding.org/famous-people-graves-disease/|title=Famous People with Graves' Disease|date=December 15, 2013|work=HRFnd|access-date=2018-02-22}}</ref><ref>{{Cite news|url=http://jewishcurrents.org/marty-feldman-versus-the-suits/|title=Marty Feldman versus the Suits|last=Kuhlenbeck|first=Mike| name-list-style = vanc |date=June 29, 2016|work=Jewish Currents|access-date=2018-02-22|language=en-US|quote=Viewers also could not help being amazed by his bulging eyes, which had resulted from a botched operation for Graves’ disease.}}</ref>
* [[Sia]], Australian singer and songwriter<ref>{{cite web |last=Rota | name-list-style = vanc |first=Genevieve |url=http://www.popsugar.com.au/celebrity/Facts-About-Sia-Songs-Sia-Furler-Has-Written-Chandelier-Clip-34816834 |title=Facts About Sia Furler | Popsugar Celebrity Australia |website=Popsugar.com.au |access-date=2016-09-10 |url-status=live |archive-url=https://web.archive.org/web/20150209012255/http://www.popsugar.com.au/celebrity/Facts-About-Sia-Songs-Sia-Furler-Has-Written-Chandelier-Clip-34816834 |archive-date=2015-02-09 }}</ref>
* [[Sammy Gravano]], Italian-American former underboss of the Gambino crime family<ref>{{cite news|url=https://pqasb.pqarchiver.com/nypost/access/112826137.html?dids=112826137:112826137&FMT=ABS&FMTS=ABS:FT&type=current&date=Mar+31%2C+2002&author=Al+Guart&pub=New+York+Post&desc=RARE+DISEASE+COULD+WHACK+SAMMY+BULL%27&pqatl=google|title=Rare Disease Could Whack Sammy Bull|last=Guart|first=Al|date=March 31, 2002|work=New York Post|access-date=January 28, 2020|archive-date=January 11, 2012|archive-url=https://web.archive.org/web/20120111205022/http://pqasb.pqarchiver.com/nypost/access/112826137.html?dids=112826137:112826137&FMT=ABS&FMTS=ABS:FT&type=current&date=Mar+31%2C+2002&author=Al+Guart&pub=New+York+Post&desc=RARE+DISEASE+COULD+WHACK+SAMMY+BULL%27&pqatl=google|url-status=dead}}</ref>
* [[Jim Hamilton (rugby union)|Jim Hamilton]], Scottish rugby player, discovered he had Graves' disease shortly after retiring from the sport in 2017.<ref>{{cite web|url=https://www.youtube.com/watch?v=yTj3JQEla-A|title=Hamilton talks about his disease on his podcast|website=[[YouTube]]|date=8 June 2017 |url-status=live|archive-url=https://web.archive.org/web/20170908171950/https://www.youtube.com/watch?v=yTj3JQEla-A|archive-date=2017-09-08}}</ref>
* [[Heino]], German folk singer, whose dark sunglasses (worn to hide his symptoms) became part of his trademark look<ref>{{cite web |url=http://www.spiegel.de/international/zeitgeist/german-crooner-heino-makes-comeback-with-hard-rock-album-a-881889.html |title=Crossover Crooner: The Strange Comeback of Germany's Wannabe Johnny Cash |publisher=Spiegel.de |date=2013-02-07 |access-date=2014-07-27 |url-status=live |archive-url=https://web.archive.org/web/20141119060602/http://www.spiegel.de/international/zeitgeist/german-crooner-heino-makes-comeback-with-hard-rock-album-a-881889.html |archive-date=2014-11-19 }}</ref>
* [[Herbert Howells]], British composer; the first person to be treated with radium injections<ref>{{Cite book|title=Herbert Howells|last=Spicer|first=Paul| name-list-style = vanc |publisher=Seren|year=1998|isbn=1-85411-233-3|location=Bridgend|pages=44}}</ref>
* [[Yayoi Kusama]], Japanese artist<ref>{{cite web |url=https://bombmagazine.org/articles/yayoi-kusama |title=Yayoi Kusama by Grady T. Turner |date=January 1, 1999|website=Bomb Magazine|access-date=May 29, 2020}}</ref>
* [[Nadezhda Krupskaya]], Russian Communist and wife of [[Vladimir Lenin]]<ref>{{cite news |url=https://www.rbth.com/arts/2017/05/18/revolutionary-first-lady-the-life-and-struggles-of-lenins-wife_765659 |title=Revolutionary First Lady: the life and struggles of Lenin's wife |newspaper=Russia Beyond |access-date=2018-04-18 |url-status=dead |archive-url=https://web.archive.org/web/20180418230109/https://www.rbth.com/arts/2017/05/18/revolutionary-first-lady-the-life-and-struggles-of-lenins-wife_765659 |archive-date=2018-04-18 }}</ref>
* [[Umm Kulthum]] was an Egyptian singer, songwriter, and film actress active from the 1920s to the 1970s.
* [[Barbara Leigh]], an American former actress and fashion model, now spokeswoman for the National Graves' Disease Foundation<ref>{{cite web |url=http://home.rmci.net/deecee/barbara_leigh.htm |title=Barbara Leigh |publisher=Home.rmci.net |access-date=2013-02-27 |url-status=dead |archive-url=https://archive.today/20120710201715/http://home.rmci.net/deecee/barbara_leigh.htm |archive-date=2012-07-10 }}</ref>
* [[Keiko Masuda]], Japanese singer and one-half of the duo [[Pink Lady (duo)|Pink Lady]].<ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110804-OYTEW53427/ |title=［歌手 増田恵子さん］バセドー病（１）マイク持つ手が震える |publisher=[[Yomiuri Shimbun]] |date=2011-08-04 |access-date=2020-02-01}}</ref><ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110811-OYTEW53431/ |title=［歌手 増田恵子さん］バセドー病（２）同じ病 姉の存在が支えに |publisher=[[Yomiuri Shimbun]] |date=2011-08-11 |access-date=2020-02-01}}</ref><ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110818-OYTEW53435/ |title=［歌手 増田恵子さん］バセドー病（３）ツアー中、甲状腺腫れ上がる |publisher=[[Yomiuri Shimbun]] |date=2011-08-18 |access-date=2020-02-01}}</ref><ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110825-OYTEW53440/ |title=［歌手 増田恵子さん］バセドー病（４）病気公表 無理せず我慢せず |publisher=[[Yomiuri Shimbun]] |date=2011-08-25 |access-date=2020-02-01}}</ref>
* [[Yūko Miyamura]], Japanese voice actress<ref>{{cite web|archive-url=https://web.archive.org/web/20070515220804/http://www3.bigcosmic.com/board/s/board.cgi?id=TSokcs&mode=cal&y=2007&m=5&d=12|archive-date=May 15, 2007|url=http://www3.bigcosmic.com/board/s/board.cgi?id=TSokcs&mode=cal&y=2007&m=5&d=12|title=親子知新|publisher=www3.bigcosmic.com|access-date=December 18, 2017}}</ref>
* [[Christopher Monckton, 3rd Viscount Monckton of Brenchley|Lord Monckton]], former [[UK Independence Party|UKIP]] and [[Conservative Party (UK)|Conservative]] politician; notorious promoter of [[Climate change denial|climate change denial]]<ref>Rupert Murray [http://www.bbc.co.uk/programmes/b00y5j3v "Meet the Climate Sceptics"] {{webarchive|url=https://web.archive.org/web/20131022043959/http://www.bbc.co.uk/programmes/b00y5j3v |date=2013-10-22 }}, ''[[Storyville (TV series)|Storyville]]'', 3 February 2011.</ref><ref>{{cite web |last1=Abraham |first1=John |title=The chief troupier: the follies of Mr Monckton |url=https://theconversation.com/the-chief-troupier-the-follies-of-mr-monckton-1555 |website=[[The Conversation (website)|The Conversation]] |publisher=The Conversation Media Group Ltd |access-date=14 August 2024 |date=22 June 2011 |quote=...in Mr. Monckton’s speeches, he cites study after study which give the impression that either climate change is not happening, or if it is, we don’t need to worry about it.}}</ref>
* [[Sophia Parnok]], Russian poet<ref>{{Cite web | url=https://www.makingqueerhistory.com/articles/2017/4/3/sophia-parnok-russias-sappho | title=Sophia Parnok, Russia's Sappho| date=3 April 2017}}</ref><ref>{{Cite journal | url=https://www.cambridge.org/core/journals/slavic-review/article/sophia-parnok-and-the-writing-of-a-lesbian-poets-life/6BB1085AA4A69E221210F210F1CF7727 |doi = 10.2307/2499528|jstor = 2499528|title = Sophia Parnok and the Writing of a Lesbian Poet's Life|year = 1992|last1 = Burgin|first1 = Diana Lewis|journal = Slavic Review|volume = 51|issue = 2|pages = 214–231| s2cid=163967264 }}</ref><ref>https://www.king.org/event/the-esoterics-parnok-in-that-infinite-moment/{{Dead link|date=November 2021 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
* [[Cecil Spring Rice|Sir Cecil Spring Rice]], British ambassador to the United States during World War I, died suddenly of the disease in 1918.<ref>{{cite news |url=https://www.telegraph.co.uk/history/10088951/This-memorial-is-poetic-justice-for-Sir-Cecil-Spring-Rice.html |title=This memorial is poetic justice for Sir Cecil Spring Rice |date=31 May 2013 |publisher=telegraph.co.uk |access-date=2014-08-25 |url-status=dead |archive-url=https://web.archive.org/web/20140312080447/http://www.telegraph.co.uk/history/10088951/This-memorial-is-poetic-justice-for-Sir-Cecil-Spring-Rice.html |archive-date=2014-03-12 |last1=Simon |first1=Bernard }}</ref>
* [[Daisy Ridley]], British actress<ref>{{cite web | url=https://www.hollywoodreporter.com/lifestyle/lifestyle-news/daisy-ridley-graves-disease-1235966996/ | title=Daisy Ridley Reveals Graves' Disease Diagnosis | website=[[The Hollywood Reporter]] | date=6 August 2024 }}</ref>
* [[Christina Rossetti]], English Victorian-era poet<ref>{{cite web |url=http://www.poetryfoundation.org/bio/christina-rossetti |title=Christina Rossetti |publisher=Poetry Foundation |access-date=2016-09-10 |url-status=live |archive-url=https://web.archive.org/web/20160417025258/http://www.poetryfoundation.org/bio/christina-rossetti |archive-date=2016-04-17 }}</ref>
* [[Maggie Smith|Dame Maggie Smith]], British actress<ref>{{cite news|url=https://www.nytimes.com/1990/03/18/magazine/there-is-nothing-like-this-dame.html|title=There is Nothing Like This Dame|last=Wolf|first=Matt | name-list-style = vanc |newspaper=New York Times|date=March 18, 1990|access-date=2015-10-19|url-status=live|archive-url=https://web.archive.org/web/20160810160402/http://www.nytimes.com/1990/03/18/magazine/there-is-nothing-like-this-dame.html|archive-date=August 10, 2016}}</ref>
* [[Mary Webb]], British novelist and poet<ref>{{cite web |url=http://www.marywebbsociety.co.uk/biography/ |title=Biography |access-date=2015-07-16 |url-status=live |archive-url=https://web.archive.org/web/20150716204649/http://www.marywebbsociety.co.uk/biography/ |archive-date=2015-07-16 }}</ref>
* [[Wendy Williams]], American TV show host<ref>{{cite web|url=https://us.cnn.com/2018/02/21/entertainment/wendy-williams-graves-disease/index.html|title=Wendy Williams announces show hiatus due to Graves' disease|last=Melas|first=Chloe | name-list-style = vanc |date=February 21, 2018|website=CNN|access-date=February 21, 2018}}</ref>
* [[Act Yasukawa]], Japanese professional wrestler<ref>{{cite web|url=https://theovertimer.com/2020/11/act-yasukawa-returns-to-ring-after-five-years-away//|title=Act Yasukawa Returns To Ring After Five Years Away|date=15 November 2020}}</ref>
<!-- NB! - alphabetical order by surname, please – thanks -->
=== Literature ===
* In [[Italo Svevo]]'s novel ''[[Zeno's Conscience]]'', character Ada develops the disease.<ref>{{cite book |last1=Svevo |first1=Italo |title=Zeno's conscience : a novel |year=2003 |publisher=Vintage Books |isbn=0375727760 |pages=315–321 |edition=1st Vintage International}}</ref><ref>{{cite web |last1=Scarponi |first1=Mattia |title=Il morbo di Basedow: lo sfinimento tra Zeno e la realtà |url=https://www.thewisemagazine.it/2017/08/19/morbo-di-basedow-sfinimento-zeno-realta/ |website=theWise Magazine |access-date=25 March 2020 |language=it-IT |date=19 August 2017}}</ref>
* [[Ern Malley]] was an acclaimed Australian poet whose work was not published until after his death from Graves' disease in 1943. However, Malley's existence and entire biography was actually later revealed to be a [[literary hoax]].
==Research==
Agents that act as antagonists at thyroid stimulating hormone receptors are under investigation as a possible treatment for Graves' disease.<ref>{{cite web|title=Thyroid|url=http://www.mayo.edu/research/departments-divisions/department-internal-medicine/division-endocrinology-diabetes-metabolism-nutrition/thyroid|website=Mayo Clinic|access-date=1 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161104001231/http://www.mayo.edu/research/departments-divisions/department-internal-medicine/division-endocrinology-diabetes-metabolism-nutrition/thyroid|archive-date=4 November 2016}}</ref>
== References ==
{{Reflist}}
== External links ==
* {{cite web | url = https://ghr.nlm.nih.gov/condition/graves-disease | publisher = U.S. National Library of Medicine | work = Genetics Home Reference | title = Graves' disease }}
* https://www.ncbi.nlm.nih.gov/gene/?term=graves about graves on ncbi
{{Medical condition classification and resources
| Curlie = Health/Conditions_and_Diseases/Endocrine_Disorders/Thyroid/Hyperthyroidism/Graves%27_Disease/
| ICD10 = {{ICD10|E|05|0|e|00}}
| ICD9 = {{ICD9|242.0}}
| ICDO =
| DiseasesDB = 5419
| OMIM = 275000
| MedlinePlus = 000358
| eMedicineSubj = med
| eMedicineTopic = 929
| eMedicine_mult = {{eMedicine2|ped|899}}
| MeshID = D006111
| SNOMED CT = 353295004
|ICD11={{ICD11|5A02.0}}|ICD10CM={{ICD10CM|E05.0}}}}
{{Thyroid disease}}
{{Autoimmune diseases}}
{{Authority control}}
{{DEFAULTSORT:Graves disease}}
[[Category:Autoimmune diseases]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Thyroid disease]]' |
New page wikitext, after the edit (new_wikitext) | '{{short description|Autoimmune endocrine disease}}
{{Infobox medical condition (new)
| name = Graves' disease
| synonyms = Toxic diffuse goiter, <br />Flajani–Basedow–Graves disease
| image = Proptosis and lid retraction from Graves' Disease.jpg
| caption = The classic finding of [[exophthalmos]] and lid retraction in Graves' disease
| field = [[Endocrinology]]
| symptoms = [[goitre|Enlarged thyroid]], [[irritability]], [[myopathy|muscle weakness]], [[insomnia|sleeping problems]], [[tachycardia|fast heartbeat]], [[weight loss]], [[heat intolerance|poor tolerance of heat]],<ref name=NIH2012/> [[anxiety]], tremor of hands or fingers, warm and moist skin, increased [[perspiration]], [[goiter]], changes in menstrual cycle, easy bruising, [[erectile dysfunction]], reduced libido, frequent bowel movements, bulging eyes ([[Graves' ophthalmopathy]]), thick red skin on shins or the top of foot ([[pretibial myxedema]])<ref name="AR">{{cite web |title=Graves' disease |url=https://www.autoimmuneregistry.org/graves-disease |access-date=15 June 2022 |website=Autoimmune Registry Inc.}}</ref>
| complications = [[Graves' ophthalmopathy]]<ref name=NIH2012/>
| onset =
| duration =
| causes = Unknown<ref name=Men2014/>
| risks = Family history, other [[autoimmune disease]]s<ref name=NIH2012/>
| diagnosis = Blood tests, [[radioiodine]] uptake<ref name=NIH2012/><ref name=NEJM2008/>
| differential =
| prevention =
| treatment = [[Radioiodine therapy]], [[antithyroid agents|antithyroid]] and [[beta blocker]] medications, [[thyroidectomy|thyroid surgery]]<ref name=NIH2012/>
| medication =
| prognosis =
| frequency = 0.5% (males), 3% (females)<ref name=Hen2015/>
| deaths =
}}
<!-- Definition and symptoms -->
'''Graves' disease''', also known as '''toxic diffuse goiter''' or '''Basedow’s disease''', is an [[autoimmune disease]] that affects the [[thyroid]].<ref name=NIH2012/> It frequently results in and is the most common cause of [[hyperthyroidism]].<ref name=Hen2015/> It also often results in an [[goitre|enlarged thyroid]].<ref name=NIH2012/> Signs and symptoms of hyperthyroidism may include [[irritability]], [[myopathy|muscle weakness]], [[insomnia|sleeping problems]], a [[tachycardia|fast heartbeat]], [[heat intolerance|poor tolerance of heat]], [[diarrhea]] and [[weight loss#unintentional|unintentional weight loss]].<ref name=NIH2012/> Other symptoms may include thickening of the skin on the shins, known as [[pretibial myxedema]], and [[exophthalmos|eye bulging]], a condition caused by [[Graves' ophthalmopathy]].<ref name=NIH2012/> About 25 to 30% of people with the condition develop eye problems.<ref name=NIH2012>{{cite web|title = Graves Disease|url = http://www.niddk.nih.gov/health-information/health-topics/endocrine/graves-disease/Pages/fact-sheet.aspx|website = www.niddk.nih.gov|access-date = 2015-04-02|date = August 10, 2012|url-status = dead|archive-url = https://web.archive.org/web/20150402223830/http://www.niddk.nih.gov/health-information/health-topics/endocrine/graves-disease/Pages/fact-sheet.aspx|archive-date = April 2, 2015}}</ref><ref name=NEJM2008/>
<!-- Cause -->The exact cause of the disease is unclear, but symptoms are a result of antibodies binding to receptors on the thyroid causing over-expression of thyroid hormone.<ref name=Men2014>{{cite journal | vauthors = Menconi F, Marcocci C, Marinò M | title = Diagnosis and classification of Graves disease | journal = Autoimmunity Reviews | volume = 13 | issue = 4–5 | pages = 398–402 | date = 2014 | pmid = 24424182 | doi = 10.1016/j.autrev.2014.01.013 }}</ref> Persons are more likely to be affected if they have a family member with the disease.<ref name=NIH2012/> If one [[identical twin|monozygotic twin]] is affected, a 30% chance exists that the other twin will also have the disease.<ref name=Nik2012/> The onset of disease may be triggered by physical or emotional stress, infection, or [[childbirth|giving birth]].<ref name=NEJM2008/> Those with other autoimmune diseases, such as [[type 1 diabetes]] and [[rheumatoid arthritis]], are more likely to be affected.<ref name=NIH2012/> Smoking increases the risk of disease and may worsen eye problems.<ref name=NIH2012/> The disorder results from an [[antibody]], called thyroid-stimulating immunoglobulin (TSI), that has a similar effect to [[thyroid stimulating hormone]] (TSH).<ref name=NIH2012/> These TSI antibodies cause the [[thyroid gland]] to produce excess [[thyroid hormones]].<ref name=NIH2012/> The diagnosis may be suspected based on symptoms and confirmed with blood tests and [[radioiodine]] uptake.<ref name=NIH2012/><ref name=NEJM2008>{{cite journal | vauthors = Brent GA | title = Clinical practice. Grave disease | journal = The New England Journal of Medicine | volume = 358 | issue = 24 | pages = 2594–605 | date = June 2008 | pmid = 18550875 | doi = 10.1056/NEJMcp0801880 }}</ref> Typically, blood tests show a raised [[triiodothyronine|T<sub>3</sub>]] and [[thyroxine|T<sub>4</sub>]], low TSH, increased radioiodine uptake in all areas of the thyroid, and TSI antibodies.<ref name=NEJM2008/>
<!-- Prevention and treatment -->
The three treatment options are [[radioiodine therapy]], medications, and [[thyroidectomy|thyroid surgery]].<ref name=NIH2012/> Radioiodine therapy involves taking [[iodine-131]] by mouth, which is then concentrated in the thyroid and destroys it over weeks to months.<ref name=NIH2012/> The resulting [[hypothyroidism]] is treated with [[thyroid hormone#Medical use|synthetic thyroid hormones]].<ref name=NIH2012/> Medications such as [[beta blockers]] may control some of the symptoms, and [[anti-thyroid medication|antithyroid medication]]s such as [[methimazole]] may temporarily help people, while other treatments are having effect.<ref name=NIH2012/> Surgery to remove the thyroid is another option.<ref name=NIH2012/> Eye problems may require additional treatments.<ref name=NIH2012/>
<!-- Epidemiology and history -->
Graves disease develops in about 0.5% of males and 3.0% of females.<ref name=Hen2015>{{cite journal | vauthors = Burch HB, Cooper DS | title = Management of Graves Disease: A Review | journal = JAMA | volume = 314 | issue = 23 | pages = 2544–54 | date = December 2015 | pmid = 26670972 | doi = 10.1001/jama.2015.16535 }}</ref> It occurs about 7.5 times more often in women than in men.<ref name=NIH2012/> Often, it starts between the ages of 40 and 60, but can begin at any age.<ref name=Nik2012/> It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).<ref name=NIH2012/><ref name=NEJM2008/> The condition is named after Irish surgeon [[Robert James Graves|Robert Graves]], who described it in 1835.<ref name=Nik2012/> A number of prior descriptions also exist.<ref name=Nik2012>{{cite book|last1=Nikiforov|first1=Yuri E.|last2=Biddinger|first2=Paul W.|last3=Nikiforova|first3=Lester D.R.|last4=Biddinger|first4=Paul W. | name-list-style = vanc |title=Diagnostic pathology and molecular genetics of the thyroid|date=2012|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=9781451114553|page=69|edition=2nd|url=https://books.google.com/books?id=jX1h00B4QJoC&pg=PA69|url-status=live|archive-url=https://web.archive.org/web/20170908171950/https://books.google.com/books?id=jX1h00B4QJoC&pg=PA69|archive-date=2017-09-08}}</ref>
==Signs and symptoms==
{{Main|Signs and symptoms of Graves' disease}}
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==Cause==
The exact cause is unclear, but it is believed to involve a combination of genetic and environmental factors.<ref name=Men2014/> While a theoretical mechanism occurs by which exposure to severe stressors and high levels of subsequent distress such as [[post-traumatic stress disorder]] <!-- (PTSD) --> could increase the risk of immune disease and cause an aggravation of the autoimmune response that leads to Graves disease, more robust clinical data are needed for a firm conclusion.<ref>{{cite journal | vauthors = Falgarone G, Heshmati HM, Cohen R, Reach G | title = Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves' disease | journal = European Journal of Endocrinology | volume = 168 | issue = 1 | pages = R13-8 | date = January 2013 | pmid = 23027804 | doi = 10.1530/EJE-12-0539 | doi-access = free }}</ref>
===Genetics===
A [[genetics|genetic]] predisposition for Graves' disease is seen, with some people more prone to develop [[thyrotropin receptor|TSH receptor]]-activating antibodies due to a genetic cause. [[Human leukocyte antigen]] DR (especially DR3) appears to play a role.<ref name="EndocrReview1993">{{cite journal | vauthors = Tomer Y, Davies TF | title = Infection, thyroid disease, and autoimmunity | journal = Endocrine Reviews | volume = 14 | issue = 1 | pages = 107–20 | date = February 1993 | doi = 10.1210/edrv-14-1-107 | pmid = 8491150 }}</ref> To date, no clear genetic defect has been found to point to a [[Monogenic (genetics)|single-gene]] cause.{{citation needed|date=June 2022}}
Genes believed to be involved include those for [[thyroglobulin]], [[thyrotropin receptor]], [[protein tyrosine phosphatase]] nonreceptor type 22 (''[[PTPN22]]''), and [[cytotoxic T-lymphocyte–associated antigen 4]], among others.<ref name=NEJM2016>{{cite journal | vauthors = Smith TJ, Hegedüs L | title = Graves' Disease | journal = The New England Journal of Medicine | volume = 375 | issue = 16 | pages = 1552–1565 | date = October 2016 | pmid = 27797318 | doi = 10.1056/NEJMra1510030 | url = https://findresearcher.sdu.dk:8443/ws/files/128446579/Graves_Disease.pdf | access-date = 2020-05-29 | archive-date = 2020-08-01 | archive-url = https://web.archive.org/web/20200801093036/https://findresearcher.sdu.dk:8443/ws/files/128446579/Graves_Disease.pdf | url-status = dead }}</ref>
===Infectious trigger===
Since Graves disease is an autoimmune disease that appears suddenly, often later in life, a [[Virus|viral]] or [[bacteria]]l infection may trigger antibodies, which cross-react with the human TSH receptor, a phenomenon known as [[antigenic mimicry]].<ref>{{cite journal | vauthors = Desailloud R, Hober D | title = Viruses and thyroiditis: an update | journal = Virology Journal | volume = 6 | pages = 5 | date = January 2009 | pmid = 19138419 | pmc = 2654877 | doi = 10.1186/1743-422X-6-5 | doi-access = free }}</ref>
The bacterium ''[[Yersinia enterocolitica]]'' bears structural similarity with the human thyrotropin receptor<ref name="EndocrReview1993"/> and was hypothesized to contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals.<ref>{{cite journal | vauthors = Toivanen P, Toivanen A | title = Does Yersinia induce autoimmunity? | journal = International Archives of Allergy and Immunology | volume = 104 | issue = 2 | pages = 107–11 | year = 1994 | pmid = 8199453 | doi = 10.1159/000236717 }}</ref>
In the 1990s, ''Y. enterocolitica'' was suggested to be possibly [[Association (statistics)|associated]] with Graves' disease.<ref>{{cite journal | vauthors = Strieder TG, Wenzel BE, Prummel MF, Tijssen JG, Wiersinga WM | title = Increased prevalence of antibodies to enteropathogenic Yersinia enterocolitica virulence proteins in relatives of patients with autoimmune thyroid disease | journal = Clinical and Experimental Immunology | volume = 132 | issue = 2 | pages = 278–82 | date = May 2003 | pmid = 12699417 | pmc = 1808711 | doi = 10.1046/j.1365-2249.2003.02139.x }}</ref>
More recently, the role for ''Y. enterocolitica'' has been disputed.<ref>{{cite journal | vauthors = Hansen PS, Wenzel BE, Brix TH, Hegedüs L | title = Yersinia enterocolitica infection does not confer an increased risk of thyroid antibodies: evidence from a Danish twin study | journal = Clinical and Experimental Immunology | volume = 146 | issue = 1 | pages = 32–8 | date = October 2006 | pmid = 16968395 | pmc = 1809723 | doi = 10.1111/j.1365-2249.2006.03183.x }}</ref>
[[Epstein–Barr virus]] <!-- (EBV) --> is another potential trigger.<ref>{{cite book |last1=Moore |first1=Elaine A. |last2=Moore |first2=Lisa Marie | name-list-style = vanc |title=Advances in Graves' Disease and Other Hyperthyroid Disorders |date=2013 |publisher=McFarland |isbn=9780786471898 |page=77 |url=https://books.google.com/books?id=0YMoAQAAQBAJ&pg=PA77 |language=en}}</ref>
==Mechanism==
Thyroid-stimulating immunoglobulins recognize and bind to the TSH receptor, which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3). Thyroxine receptors in the pituitary gland are activated by the surplus hormone, suppressing additional release of TSH in a negative feedback loop. The result is very high levels of circulating thyroid hormones and a low TSH level.{{citation needed|date=July 2022}}
===Pathophysiology===
[[File:Histopathology of Graves' disease - medium mag.jpg|thumb|Histopathology of a case of Grave's disease. It shows marked hyperplasia of [[thyroid follicular cell]]s, generally more so than [[toxic multinodular goitre]], forming papillae into the thyroid follicles, and with scalloping of the peripheral colloid.]]
Graves' disease is an [[autoimmunity|autoimmune]] disorder, in which the body produces [[antibody|antibodies]] that are specific to a [[self-protein]] - the receptor for thyroid-stimulating hormone. (Antibodies to thyroglobulin and to the [[thyroid hormone]]s T3 and T4 may also be produced.)
These antibodies cause hyperthyroidism because they bind to the TSHr and [[chronic (medicine)|chronically]] stimulate it. The TSHr is expressed on the [[thyroid follicular cell]]s of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4. This, in turn, causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.
The infiltrative exophthalmos frequently encountered has been explained by postulating that the thyroid gland and the extraocular muscles share a common antigen, which is recognized by the antibodies. Antibodies binding to the extraocular muscles would cause swelling behind the eyeball.
The "orange peel" skin has been explained by the infiltration of antibodies under the skin, causing an inflammatory reaction and subsequent fibrous plaques.
'''The three types of autoantibodies to the TSH receptor are:'''
# '''Thyroid stimulating immunoglobulins:''' these antibodies (mainly IgG) act as long-acting thyroid stimulants, activating the cells through a slower and more drawn out process compared to TSH, leading to an elevated production of thyroid hormone.
# '''Thyroid growth immunoglobulins:''' these antibodies bind directly to the TSH receptor and have been implicated in the growth of thyroid follicles.
# '''Thyrotrophin binding-inhibiting immunoglobulins:''' these antibodies inhibit the normal union of TSH with its receptor.
#* Some actually act as if TSH itself is binding to its receptor, thus inducing thyroid function.
#* Other types may not stimulate the thyroid gland, but <u>prevent</u> TSI and TSH from binding to and stimulating the receptor.
Another effect of hyperthyroidism is bone loss from osteoporosis, caused by an increased excretion of calcium and phosphorus in the urine and stool. The effects can be minimized if the hyperthyroidism is treated early. [[Thyrotoxicosis]] can also augment calcium levels in the blood by as much as 25%. This can cause stomach upset, excessive urination, and impaired kidney function.<ref>{{cite web |url=http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |title=Thyroid Disease, Osteoporosis and Calcium – Womens Health and Medical Information on |publisher=Medicinenet.com |date=2006-12-07 |access-date=2013-02-27 |url-status=live |archive-url=https://web.archive.org/web/20130307133403/http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |archive-date=2013-03-07 }}</ref>
==Diagnosis==
Graves disease may present clinically with one or more of these characteristic signs:{{citation needed|date=June 2022}}
* Rapid heartbeat (80%)
* Diffuse palpable goiter with audible [[bruit]] (70%)
* Tremor (40%)
* [[Exophthalmos]] (protuberance of one or both eyes), periorbital edema (25%)
* Fatigue (70%), weight loss (60%) with increased appetite in young people and poor appetite in the elderly, and other symptoms of hyperthyroidism/[[thyrotoxicosis]]
* Heat intolerance (55%)
* Tremulousness (55%)
* Palpitations (50%)
Two signs are truly diagnostic of Graves' disease (i.e., not seen in other hyperthyroid conditions): exophthalmos and non-pitting edema ([[pretibial myxedema]]). Goiter is an enlarged thyroid gland and is of the diffuse type (i.e., spread throughout the gland). Diffuse goiter may be seen with other causes of hyperthyroidism, although Graves' disease is the most common cause of diffuse goiter. A large goiter will be visible to the naked eye, but a small one (mild enlargement of the gland) may be detectable only by physical examination. Occasionally, goiter is not clinically detectable, but may be seen only with [[computed tomography]] or [[ultrasound]] examination of the thyroid.{{citation needed|date=June 2022}} Another sign of Graves' disease is hyperthyroidism, that is, overproduction of the thyroid hormones T3 and T4. Normal thyroid levels are also seen, and occasionally also hypothyroidism, which may assist in causing goiter (though it is not the cause of the Graves' disease). Hyperthyroidism in Graves' disease is confirmed, as with any other cause of hyperthyroidism, by measuring elevated blood levels of free (unbound) T3 and T4.{{citation needed|date=June 2022}}
Other useful laboratory measurements in Graves disease include thyroid-stimulating hormone (TSH, usually undetectable in Graves disease due to [[negative feedback]] from the elevated T3 and T4), and protein-bound [[iodine]] (elevated). [[serology|Serologically]] detected thyroid-stimulating antibodies, radioactive iodine <!-- (RAI) --> uptake, or thyroid [[Doppler ultrasonography|ultrasound with Doppler]] all can independently confirm a diagnosis of Graves disease.
[[Biopsy]] to obtain histiological testing is not normally required, but may be obtained if thyroidectomy is performed.<!-- see eMedicine/med/topic929 of infobox -->
The goiter in Graves disease is often not nodular, but [[thyroid nodule]]s are also common.<ref name="pmid_9709909">{{cite journal | vauthors = Carnell NE, Valente WA | title = Thyroid nodules in Graves' disease: classification, characterization, and response to treatment | journal = Thyroid | volume = 8 | issue = 7 | pages = 571–6 | date = July 1998 | pmid = 9709909 | doi = 10.1089/thy.1998.8.571 }}</ref> Differentiating common forms of hyperthyroidism such as Graves' disease, single [[thyroid adenoma]], and [[toxic multinodular goiter]] is important to determine proper treatment.<ref name="pmid_9709909"/> The [[toxic multinodular goitre#Differentiation and terminology among types of goiter|differentiation among these entities has advanced]], as imaging and biochemical tests have improved. Measuring TSH-receptor antibodies with the h-TBII assay has been proven efficient and was the most practical approach found in one study.<ref name="pmid_15127319">{{cite journal | vauthors = Wallaschofski H, Kuwert T, Lohmann T | title = TSH-receptor autoantibodies - differentiation of hyperthyroidism between Graves' disease and toxic multinodular goitre | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 112 | issue = 4 | pages = 171–4 | date = April 2004 | pmid = 15127319 | doi = 10.1055/s-2004-817930 }}</ref>
===Eye disease===
{{Further|Graves ophthalmopathy|}}
Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease (TED), is the most common extrathyroidal manifestation of Graves' disease. It is a form of [[Idiopathic orbital inflammatory disease|idiopathic lymphocytic orbital inflammation]], and although its pathogenesis is not completely understood, autoimmune activation of orbital [[fibroblast]]s, which in TAO express the [[Thyrotropin receptor|TSH receptor]], is thought to play a central role.<ref>{{cite journal | vauthors = Shan SJ, Douglas RS | title = The pathophysiology of thyroid eye disease | journal = Journal of Neuro-Ophthalmology | volume = 34 | issue = 2 | pages = 177–85 | date = June 2014 | pmid = 24821101 | doi = 10.1097/wno.0000000000000132 | s2cid = 10998666 | doi-access = free }}</ref>
[[Hypertrophy]] of the extraocular muscles, [[adipogenesis]], and deposition of nonsulfated [[glycosaminoglycan]]s and hyaluronate, causes expansion of the orbital fat and muscle compartments, which within the confines of the bony orbit may lead to [[Optic neuropathy|dysthyroid optic neuropathy]], increased [[Glaucoma|intraocular pressures]], proptosis, venous congestion leading to chemosis and periorbital edema, and progressive remodeling of the orbital walls.<ref>{{cite journal | vauthors = Feldon SE, Muramatsu S, Weiner JM | title = Clinical classification of Graves' ophthalmopathy. Identification of risk factors for optic neuropathy | journal = Archives of Ophthalmology | volume = 102 | issue = 10 | pages = 1469–72 | date = October 1984 | pmid = 6548373 | doi = 10.1001/archopht.1984.01040031189015 }}</ref><ref>{{cite journal | vauthors = Gorman CA | title = The measurement of change in Graves' ophthalmopathy | journal = Thyroid | volume = 8 | issue = 6 | pages = 539–43 | date = June 1998 | pmid = 9669294 | doi = 10.1089/thy.1998.8.539 }}</ref><ref>{{cite journal | vauthors = Tan NY, Leong YY, Lang SS, Htoon ZM, Young SM, Sundar G | title = Radiologic Parameters of Orbital Bone Remodeling in Thyroid Eye Disease | journal = Investigative Ophthalmology & Visual Science | volume = 58 | issue = 5 | pages = 2527–2533 | date = May 2017 | pmid = 28492870 | doi = 10.1167/iovs.16-21035 | doi-access = free }}</ref> Other distinctive features of TAO include lid retraction, restrictive myopathy, superior limbic keratoconjunctivitis, and [[exposure keratopathy]].{{citation needed|date=June 2022}}
Severity of eye disease may be classified by the mnemonic: "NO SPECS":<ref name="pmid15310608">{{cite journal | vauthors = Cawood T, Moriarty P, O'Shea D | title = Recent developments in thyroid eye disease | journal = BMJ | volume = 329 | issue = 7462 | pages = 385–90 | date = August 2004 | pmid = 15310608 | pmc = 509348 | doi = 10.1136/bmj.329.7462.385 }}</ref>
* Class 0: No signs or symptoms
* Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)
* Class 2: Soft tissue involvement ([[oedema]] of [[conjunctiva]]e and lids, conjunctival injection, etc.)
* Class 3: [[Proptosis]]
* Class 4: [[Extraocular muscle]] involvement (usually with [[diplopia]])
* Class 5: Corneal involvement (primarily due to [[lagophthalmos]])
* Class 6: Sight loss (due to optic nerve involvement)
Typically, the natural history of TAO follows Rundle's curve, which describes a rapid worsening during an initial phase, up to a peak of maximum severity, and then improvement to a static plateau without, however, resolving back to a normal condition.<ref>{{cite journal | vauthors = Bartley GB | title = Rundle and his curve | journal = Archives of Ophthalmology | volume = 129 | issue = 3 | pages = 356–8 | date = March 2011 | pmid = 21402995 | doi = 10.1001/archophthalmol.2011.29 | doi-access = }}</ref>
==Management==
Treatment of Graves disease includes [[antithyroid agents|antithyroid drugs]] that reduce the production of thyroid hormone, [[radioiodine]] (radioactive iodine [[I-131]]) and [[thyroidectomy]] (surgical excision of the gland). As operating on a hyperthyroid patient is dangerous, prior to thyroidectomy, preoperative treatment with antithyroid drugs is given to render the patient euthyroid. Each of these treatments has advantages and disadvantages, and no single treatment approach is considered the best for everyone.{{citation needed|date=June 2022}}
Treatment with antithyroid medications must be administered for six months to two years to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. The risk of recurrence is about 40–50%, and lifelong treatment with antithyroid drugs carries some side effects such as [[agranulocytosis]] and [[liver disease]].<ref name=":0">{{cite journal | vauthors = Stathopoulos P, Gangidi S, Kotrotsos G, Cunliffe D | title = Graves' disease: a review of surgical indications, management, and complications in a cohort of 59 patients | journal = International Journal of Oral and Maxillofacial Surgery | volume = 44 | issue = 6 | pages = 713–7 | date = June 2015 | pmid = 25726089 | doi = 10.1016/j.ijom.2015.02.007 }}</ref> Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells. Therapy with radioiodine is the most common treatment in the United States, while antithyroid drugs and/or thyroidectomy are used more often in Europe, Japan, and most of the rest of the world.
[[beta blocker|β-Blockers]] (such as [[propranolol]]) may be used to inhibit the [[sympathetic nervous system]] symptoms of [[tachycardia]] and nausea until antithyroid treatments start to take effect. Pure β-blockers do not inhibit lid retraction in the eyes, which is mediated by alpha adrenergic receptors.
===Antithyroid drugs===
The main antithyroid drugs are [[carbimazole]] (in the UK), [[methimazole]] (in the US), and [[propylthiouracil]]/PTU. These drugs block the binding of iodine and coupling of iodotyrosines. The most dangerous side effect is agranulocytosis (1/250, more in PTU). Others include [[neutropenia|granulocytopenia]] (dose-dependent, which improves on cessation of the drug) and [[aplastic anemia]]. Patients on these medications should see a doctor if they develop sore throat or fever. The most common side effects are rash and [[Peripheral neuropathy|peripheral neuritis]]. These drugs also cross the [[placenta]] and are secreted in breast milk. [[Lugol's iodine]] may be used to block hormone synthesis before surgery.{{citation needed|date=June 2022}}
A [[randomized control trial]] testing single-dose treatment for Graves found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).<ref name="pmid11298092">{{cite journal | vauthors = Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A | title = Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism | journal = Clinical Endocrinology | volume = 54 | issue = 3 | pages = 385–90 | date = March 2001 | pmid = 11298092 | doi = 10.1046/j.1365-2265.2001.01239.x | s2cid = 24463399 }}</ref>
No difference in outcome was shown for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are a positive [[Thyrotropin receptor|TSHr]] [[antibody]] (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% ([[sensitivity and specificity|sensitivity]] 39%, [[sensitivity and specificity|specificity]] 98%), and a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.<ref name="pmid11331213">{{cite journal | vauthors = Glinoer D, de Nayer P, Bex M | title = Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study | journal = European Journal of Endocrinology | volume = 144 | issue = 5 | pages = 475–83 | date = May 2001 | pmid = 11331213 | doi = 10.1530/eje.0.1440475 | doi-access = free }}</ref>
===Radioiodine===
[[Image:Basedow-vor-nach-RIT.jpg|thumb|Scan of affected thyroid before (''top'') and after (''bottom'') [[radioiodine]] therapy]]
Radioiodine (radioactive iodine-131) was developed in the early 1940s at the [[Mallinckrodt General Clinical Research Center]]. This modality is suitable for most patients, although some prefer to use it mainly for older patients. Indications for radioiodine are failed medical therapy or surgery and where medical or surgical therapy are contraindicated. Hypothyroidism may be a complication of this therapy, but may be treated with thyroid hormones if it appears. The rationale for radioactive iodine is that it accumulates in the thyroid and irradiates the gland with its beta and gamma radiations, about 90% of the total radiation being emitted by the beta (electron) particles. The most common method of iodine-131 treatment is to administer a specified amount in microcuries per gram of thyroid gland based on palpation or radiodiagnostic imaging of the gland over 24 hours.<ref>{{cite book|last=Saha|first=Gopal B. | name-list-style = vanc |title=Fundamentals of Nuclear Pharmacy|edition=5|year=2009|publisher=Springer-Verlag New York, LLC|isbn=978-0387403601|page=342}}</ref> Patients who receive the therapy must be monitored regularly with thyroid blood tests to ensure they are treated with thyroid hormone before they become symptomatically hypothyroid.<ref>{{cite journal | vauthors = Schäffler A | title = Hormone replacement after thyroid and parathyroid surgery | journal = Deutsches Ärzteblatt International | volume = 107 | issue = 47 | pages = 827–34 | date = November 2010 | pmid = 21173898 | pmc = 3003466 | doi = 10.3238/arztebl.2010.0827 }}</ref>
Contraindications to RAI are [[pregnancy]] (absolute), ophthalmopathy (relative; it can aggravate thyroid eye disease), or solitary [[thyroid nodule|nodules]].<ref name="btf-thyroid.org">{{cite web |url=http://www.btf-thyroid.org/information/leaflets/39-radioactive-iodine-guide |title=Treatment of an Over-active or Enlarged Thyroid Gland with Radioactive Iodine – British Thyroid Foundation |website=Btf-thyroid.org |access-date=2016-09-10 |url-status=live |archive-url=https://web.archive.org/web/20160902004052/http://www.btf-thyroid.org/information/leaflets/39-radioactive-iodine-guide |archive-date=2016-09-02 }}</ref>
Disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring eventual thyroid hormone supplementation in the form of a daily pill(s). The radioiodine treatment acts slowly (over months to years) to destroy the thyroid gland, and Graves' disease–associated hyperthyroidism is not cured in all persons by radioiodine, but has a relapse rate that depends on the dose of radioiodine which is administered.<ref name="btf-thyroid.org"/> In rare cases, [[Radiation-induced thyroiditis|radiation induced thyroiditis]] has been linked to this treatment.<ref>{{Cite journal|last1=Mizokami|first1=Tetsuya|last2=Hamada|first2=Katsuhiko|last3=Maruta|first3=Tetsushi|last4=Higashi|first4=Kiichiro|last5=Tajiri|first5=Junichi|date=September 2016|title=Painful Radiation Thyroiditis after 131I Therapy for Graves' Hyperthyroidism: Clinical Features and Ultrasonographic Findings in Five Cases|journal=European Thyroid Journal|volume=5|issue=3|pages=201–206|doi=10.1159/000448398|issn=2235-0640|pmc=5091234|pmid=27843811}}</ref>
===Surgery===
{{Further|Thyroidectomy|}}
This modality is suitable for young people and pregnant females. Indications for thyroidectomy can be separated into absolute indications or relative indications. These indications aid in deciding which people would benefit most from surgery.<ref name=":0" /> The absolute indications are a large goiter (especially when compressing the [[vertebrate trachea|trachea]]), suspicious nodules or suspected [[cancer]] (to pathologically examine the thyroid), and people with ophthalmopathy and additionally if it is the person's preferred method of treatment or if refusing to undergo radioactive iodine treatment. Pregnancy is advised to be delayed for six months after radioactive iodine treatment.<ref name=":0" />
Both bilateral subtotal [[thyroidectomy]] and the Hartley-Dunhill procedure (hemithyroidectomy on one side and partial lobectomy on other side) are possible.
Advantages are immediate cure and potential removal of [[carcinoma]]. Its risks are injury of the [[recurrent laryngeal nerve]], [[hypoparathyroidism]] (due to removal of the [[parathyroid gland]]s), [[hematoma]] (which can be life-threatening if it compresses the trachea), relapse following medical treatment, infections (less common), and [[scarring]].<ref name=":0" /> The increase in the risk of nerve injury can be due to the increased vascularity of the thyroid parenchyma and the development of links between the thyroid capsule and the surrounding tissues. Reportedly, a 1% incidence exists of permanent [[Vocal fold paresis|recurrent laryngeal nerve paralysis]] after complete thyroidectomy.<ref name=":0" /> Risks related to anesthesia are many, thus coordination with the anesthesiologist and patient optimization for surgery preoperatively are essential. Removal of the gland enables complete biopsy to be performed to have definite evidence of cancer anywhere in the thyroid. (Needle biopsies are not so accurate at predicting a benign state of the thyroid). No further treatment of the thyroid is required, unless cancer is detected. Radioiodine uptake study may be done after surgery, to ensure all remaining (potentially cancerous) thyroid cells (i.e., near the nerves to the vocal cords) are destroyed. Besides this, the only remaining treatment will be [[levothyroxine]], or thyroid replacement pills to be taken for the rest of the patient's life.
A 2013 review article concludes that surgery appears to be the most successful in the management of Graves' disease, with total thyroidectomy being the preferred surgical option.<ref>{{cite journal | vauthors = Genovese BM, Noureldine SI, Gleeson EM, Tufano RP, Kandil E | title = What is the best definitive treatment for Graves' disease? A systematic review of the existing literature | journal = Annals of Surgical Oncology | volume = 20 | issue = 2 | pages = 660–7 | date = February 2013 | pmid = 22956065 | doi = 10.1245/s10434-012-2606-x | s2cid = 24759725 | type = review }}</ref>
===Eyes===
Mild cases are treated with lubricant eye drops or nonsteroidal anti-inflammatory drops. Severe cases threatening vision (corneal exposure or optic nerve compression) are treated with steroids or orbital decompression. In all cases, cessation of smoking is essential. Double vision can be corrected with prism glasses and surgery (the latter only when the process has been stable for a while).
Difficulty closing eyes can be treated with lubricant gel at night, or with tape on the eyes to enable full, deep sleep.
Orbital decompression can be performed to enable bulging eyes to retreat back into the head. Bone is removed from the skull behind the eyes, and space is made for the muscles and fatty tissue to fall back into the skull. <ref>{{Cite journal |last1=Limongi |first1=Roberto Murillo |last2=Feijó |first2=Eduardo Damous |last3=Rodrigues Lopes E Silva |first3=Marlos |last4=Akaishi |first4=Patrícia |last5=Velasco E Cruz |first5=Antônio Augusto |last6=Christian Pieroni-Gonçalves |first6=Allan |last7=Pereira |first7=Filipe |last8=Devoto |first8=Martin |last9=Bernardini |first9=Francesco |last10=Marques |first10=Victor |last11=Tao |first11=Jeremiah P. |date=February 2020 |title=Orbital Bone Decompression for Non-Thyroid Eye Disease Proptosis |url=https://pubmed.ncbi.nlm.nih.gov/31373985/ |journal=Ophthalmic Plastic and Reconstructive Surgery |volume=36 |issue=1 |pages=13–16 |doi=10.1097/IOP.0000000000001435 |issn=1537-2677 |pmid=31373985|s2cid=199388425 }}</ref>
For management of clinically active Graves disease, orbitopathy (clinical activity score >2) with at least mild to moderate severity, intravenous glucocorticoids are the treatment of choice, usually administered in the form of pulse intravenous methylprednisolone. Studies have consistently shown that pulse intravenous methylprednisolone is superior to oral glucocorticoids both in terms of efficacy and decreased side effects for managing Graves' orbitopathy.<ref>{{cite journal | vauthors = Roy A, Dutta D, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, Chowdhury S | title = Efficacy and safety of low dose oral prednisolone as compared to pulse intravenous methylprednisolone in managing moderate severe Graves' orbitopathy: A randomized controlled trial | journal = Indian Journal of Endocrinology and Metabolism | volume = 19 | issue = 3 | pages = 351–8 | date = 2015 | pmid = 25932389 | pmc = 4366772 | doi = 10.4103/2230-8210.152770 | doi-access = free }}</ref>
==Prognosis==
If left untreated, more serious [[complications (medical)|complications]] could result, including [[birth defect]]s in pregnancy, increased risk of a [[miscarriage]], bone mineral loss<ref name=Ken2001/> and, in extreme cases, death (e.g. indirectly through complications, or through a [[thyroid storm]] event). Graves' disease is often accompanied by an increase in heart rate, which may lead to further heart complications, including loss of the normal heart rhythm (atrial fibrillation), which may lead to stroke. If the eyes are proptotic (bulging) enough that the lids do not close completely at night, dryness will occur – with the risk of a secondary corneal infection, which could lead to blindness. Pressure on the optic nerve behind the globe can lead to visual field defects and vision loss, as well. Prolonged untreated hyperthyroidism can lead to bone loss, which may resolve when treated.<ref name="Ken2001">{{Cite book |url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA636 |title=Principles and practice of endocrinology and metabolism |date=2001 |publisher=Lippincott, Williams & Wilkins |isbn=978-0-7817-1750-2 |editor-last=Becker |editor-first=Kenneth L. |edition=3 |location=Philadelphia, Pa. |page=636 |archive-url=https://web.archive.org/web/20170908171950/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA636 |archive-date=2017-09-08 |url-status=live}}</ref>
==Epidemiology==
[[File:Causes of hyperthyroidism.png|thumb|Most common causes of [[hyperthyroidism]] by age<ref>{{cite journal|last1=Carlé|first1=Allan|last2=Pedersen|first2=Inge Bülow|last3=Knudsen|first3=Nils|last4=Perrild|first4=Hans|last5=Ovesen|first5=Lars|last6=Rasmussen|first6=Lone Banke|last7=Laurberg|first7=Peter|title=Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study|journal=European Journal of Endocrinology|volume=164|issue=5|year=2011|pages=801–809|issn=0804-4643|doi=10.1530/EJE-10-1155|pmid=21357288|doi-access=free}}</ref>]]
Graves' disease occurs in about 0.5% of people.<ref name=NEJM2008/> Graves' disease data has shown that the lifetime risk for women is around 3% and 0.5% for men.<ref>{{Citation|last1=Pokhrel|first1=Binod|title=Graves Disease|date=2020|url=http://www.ncbi.nlm.nih.gov/books/NBK448195/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=28846288|access-date=2020-12-04|last2=Bhusal|first2=Kamal}}</ref> It occurs about 7.5 times more often in women than in men<ref name=NIH2012/> and often starts between the ages of 40 and 60.<ref name=Nik2012/> It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).<ref name=NIH2012/><ref name=NEJM2008/>
==History==
Graves disease owes its name to the [[Anglo-Irish]] doctor [[Robert James Graves]],<ref>{{WhoNamedIt|doctor|695|Mathew Graves}}</ref> who described a case of goiter with exophthalmos in 1835.<ref>Graves, RJ. [https://archive.org/details/p2londonmedicals07londuoft ''Newly observed affection of the thyroid gland in females''] {{webarchive|url= https://web.archive.org/web/20160331121345/https://archive.org/details/p2londonmedicals07londuoft |date= 2016-03-31 }}. (Clinical lectures.) London Medical and Surgical Journal (Renshaw), 1835; 7 (part 2): 516–517. Reprinted in Medical Classics, 1940;5:33–36.</ref> ([[Medical eponyms]] are often styled nonpossessively; thus ''Graves' disease'' and ''Graves disease'' are variant stylings of the same term.)
The German [[Karl Adolph von Basedow]] independently reported the same constellation of symptoms in 1840.<ref>Von Basedow, KA. ''Exophthalmus durch Hypertrophie des Zellgewebes in der Augenhöhle''. ''[Casper's] Wochenschrift für die gesammte Heilkunde'', Berlin, 1840, 6: 197–204; 220–228. Partial English translation in: Ralph Hermon Major (1884–1970): ''Classic Descriptions of Disease''. Springfield, C. C. Thomas, 1932. 2nd edition, 1939; 3rd edition, 1945.</ref><ref>Von Basedow, KA. "Die Glotzaugen". ''[Casper's] Wochenschrift für die gesammte Heilkunde'', Berlin, 1848: 769–777.</ref> As a result, on the European continent, the terms "Basedow syndrome",<ref name="WNI" /> "Basedow disease", or "Morbus Basedow"<ref name="TMHP">{{cite-TMHP|Exophthalmic goiter, Basedow disease, Grave disesase}}, pages 82, 294, and 295.</ref> are more common than "Graves' disease".<ref name="WNI">{{WhoNamedIt|synd|1517|Basedow syndrome or disease}} – the history and naming of the disease</ref><ref>{{eMedicine|med|917|Goiter, Diffuse Toxic}}</ref>
Graves disease<ref name=WNI/><ref name=TMHP/> has also been called ''exophthalmic goiter''.<ref name=TMHP/>
Less commonly, it has been known as Parry disease,<ref name=WNI/><ref name=TMHP/> Begbie disease, Flajan disease, Flajani–Basedow syndrome, and Marsh disease.<ref name=WNI/> These names for the disease were derived from [[Caleb Hillier Parry]], [[James Begbie]], [[Giuseppe Flajani]], and [[Sir Henry Marsh| Henry Marsh]].<ref name=WNI/> Early reports, not widely circulated, of cases of goiter with exophthalmos were published by the Italians Giuseppe Flajani<ref>Flajani, G. ''Sopra un tumor freddo nell'anterior parte del collo broncocele. (Osservazione LXVII)''. In Collezione d'osservazioni e reflessioni di chirurgia. Rome, Michele A Ripa Presso Lino Contedini, 1802;3:270–273.</ref> and Antonio Giuseppe Testa,<ref>Testa, AG. ''Delle malattie del cuore, loro cagioni, specie, segni e cura.'' Bologna, 1810. 2nd edition in 3 volumes, Florence, 1823; Milano 1831; German translation, Halle, 1813.</ref> in 1802 and 1810, respectively.<ref>{{WhoNamedIt|doctor|1471|Giuseppe Flajani}}</ref> Prior to these, Caleb Hillier Parry,<ref>{{cite book | vauthors = Parry CH | chapter = Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart | title = Collections from the unpublished medical writings of C. H. Parry | location = London | date = 1825 | pages = 111–129 | quote = According to Garrison, Parry first noted the condition in 1786. He briefly reported it in his ''Elements of Pathology and Therapeutics'', 1815. Reprinted in Medical Classics, 1940, 5: 8–30 }}</ref> a notable provincial physician in England of the late 18th century (and a friend of [[Edward Miller-Gallus]]),<ref>{{cite journal | vauthors = Hull G | title = Caleb Hillier Parry 1755-1822: a notable provincial physician | journal = Journal of the Royal Society of Medicine | volume = 91 | issue = 6 | pages = 335–8 | date = June 1998 | pmid = 9771526 | pmc = 1296785 | doi = 10.1177/014107689809100618 }}</ref> described a case in 1786. This case was not published until 1825 - ten years ahead of Graves.<ref>{{WhoNamedIt|doctor|397|Caleb Hillier Parry}}</ref>
However, fair credit for the first description of Graves disease goes to the 12th-century [[Islamic medicine |Persian physician]] [[Zayn al-Din al-Jurjani|Sayyid Ismail al-Jurjani]],<ref>Sayyid Ismail Al-Jurjani. ''Thesaurus of the Shah of Khwarazm''.</ref> who noted the association of goiter and exophthalmos in his [[Zayn al-Din al-Jurjani#Thesaurus of the Shah of Khwarazm|''Thesaurus of the Shah of Khwarazm'']], the major medical dictionary of its time.<ref name=WNI/><ref>{{cite journal | vauthors = Ljunggren JG | title = [Who was the man behind the syndrome: Ismail al-Jurjani, Testa, Flagani, Parry, Graves or Basedow? Use the term hyperthyreosis instead] | journal = Läkartidningen | volume = 80 | issue = 32–33 | pages = 2902 | date = August 1983 | pmid = 6355710 }}</ref>
==Society and culture==
=== Notable cases ===
<!-- NB! - alphabetical order by surname, and please don't add very obscure persons -->
[[File:Marty Feldman.png|thumb|upright=1.3|[[Marty Feldman]] used his bulging eyes, caused by Graves' disease, for comedic effect.]]
* [[Ayaka]], Japanese singer, was diagnosed with Graves disease in 2007. After going public with her diagnosis in 2009, she took a two-year hiatus from music to focus on treatment.<ref>{{cite web |title=水嶋ヒロ・絢香、2ショット会見で結婚報告 絢香はバセドウ病を告白、年内で休業へ |url=http://beauty.oricon.co.jp/trend-culture/trend/news/64835/full/ |publisher=[[Oricon]] |language=ja |date=April 3, 2009 |access-date=November 19, 2015 |url-status=live |archive-url=https://web.archive.org/web/20151208132540/http://beauty.oricon.co.jp/trend-culture/trend/news/64835/full/ |archive-date=December 8, 2015 }}</ref><ref>{{cite web |title=絢香、初のセルフ・プロデュース・アルバムが発売決定！ |url=http://www.cdjournal.com/main/news/ayaka/41818 |publisher=CDJournal |language=ja |date=December 1, 2011 |access-date=November 19, 2015 |url-status=live |archive-url=https://web.archive.org/web/20151015101029/http://www.cdjournal.com/main/news/ayaka/41818 |archive-date=October 15, 2015 }}</ref>
* [[Susan Blow|Susan Elizabeth Blow]], American educator and founder of the first publicly funded kindergarten in the United States, was forced to retire and seek treatment for Graves disease in 1884.<ref>{{Cite book|title=Movers and Shakers, Scalawags and Suffragettes: Tales from Bellefontaine Cemetery|last=Shepley|first=Carol Ferring|publisher=Missouri History Museum|year=2008|location=St. Louis, Missouri}}</ref>
* [[George H. W. Bush]], former U.S. president, developed new [[atrial fibrillation]] and was diagnosed in 1991 with [[hyperthyroidism]] due to the disease and treated with radioactive iodine.<ref>{{cite news|last1=Okie|first1=Susan|date=May 10, 1991|title=Bush's Thyroid Condition Diagnosed As Graves' Disease|newspaper=[[The Washington Post]]|url=https://www.washingtonpost.com/archive/politics/1991/05/10/bushs-thyroid-condition-diagnosed-as-graves-disease/d3c91174-dec2-4f01-a191-ba3e81e48e69/|url-status=live|url-access=|access-date=June 17, 2023|archive-url=https://web.archive.org/web/20180107181333/https://www.washingtonpost.com/archive/politics/1991/05/10/bushs-thyroid-condition-diagnosed-as-graves-disease/d3c91174-dec2-4f01-a191-ba3e81e48e69/|archive-date=January 7, 2018}}</ref> The president's wife, [[Barbara Bush]], also developed the disease around the same time, which, in her case, produced severe infiltrative [[exophthalmos]].<ref>{{cite news| first = Lawrence K. | last = Altman | name-list-style = vanc | url = https://www.nytimes.com/1991/05/28/science/the-doctor-s-world-a-white-house-puzzle-immunity-ailments.html |title=The Doctor's World — A White House Puzzle: Immunity Ailments-Science Section|work=[[The New York Times]]|date=1991-05-28|access-date=2013-02-27|url-status=live|archive-url=https://web.archive.org/web/20130508015248/http://www.nytimes.com/1991/05/28/science/the-doctor-s-world-a-white-house-puzzle-immunity-ailments.html|archive-date=2013-05-08}}</ref>
* [[Rodney Dangerfield]], American comedian and actor<ref>{{cite web |url=http://www.pathologyoutlines.com/topic/thyroidgraves.html |title=Thyroid gland – Hyperplasia / goiter – Graves disease | first = Shahidul | last = Islam | name-list-style = vanc |website=Pathologyoutlines.com |date=2017-01-23 |access-date=2017-01-25 |url-status=live |archive-url=https://web.archive.org/web/20161214044717/http://pathologyoutlines.com/topic/thyroidgraves.html |archive-date=2016-12-14 }}</ref>
* [[Gail Devers]], American sprinter: A doctor considered amputating her feet after she developed blistering and swelling following radiation treatment for Graves' disease, but she went on to recover and win Olympic medals.
* [[Missy Elliott]], American hip-hop artist<ref>{{cite web|last=Oldenburg |first=Ann | name-list-style = vanc |url=http://content.usatoday.com/communities/entertainment/post/2011/06/missy-elliott-reveals-graves-disease-battle/1 |title=Update: Missy Elliott 'completely managing' Graves' disease |date=2011-06-24 |work=USA Today |publisher=Gannett}}</ref>
* [[Marty Feldman]], British comedy writer, comedian and actor<ref>{{Cite news|url=https://healthresearchfunding.org/famous-people-graves-disease/|title=Famous People with Graves' Disease|date=December 15, 2013|work=HRFnd|access-date=2018-02-22}}</ref><ref>{{Cite news|url=http://jewishcurrents.org/marty-feldman-versus-the-suits/|title=Marty Feldman versus the Suits|last=Kuhlenbeck|first=Mike| name-list-style = vanc |date=June 29, 2016|work=Jewish Currents|access-date=2018-02-22|language=en-US|quote=Viewers also could not help being amazed by his bulging eyes, which had resulted from a botched operation for Graves’ disease.}}</ref>
* [[Sia]], Australian singer and songwriter<ref>{{cite web |last=Rota | name-list-style = vanc |first=Genevieve |url=http://www.popsugar.com.au/celebrity/Facts-About-Sia-Songs-Sia-Furler-Has-Written-Chandelier-Clip-34816834 |title=Facts About Sia Furler | Popsugar Celebrity Australia |website=Popsugar.com.au |access-date=2016-09-10 |url-status=live |archive-url=https://web.archive.org/web/20150209012255/http://www.popsugar.com.au/celebrity/Facts-About-Sia-Songs-Sia-Furler-Has-Written-Chandelier-Clip-34816834 |archive-date=2015-02-09 }}</ref>
* [[Sammy Gravano]], Italian-American former underboss of the Gambino crime family<ref>{{cite news|url=https://pqasb.pqarchiver.com/nypost/access/112826137.html?dids=112826137:112826137&FMT=ABS&FMTS=ABS:FT&type=current&date=Mar+31%2C+2002&author=Al+Guart&pub=New+York+Post&desc=RARE+DISEASE+COULD+WHACK+SAMMY+BULL%27&pqatl=google|title=Rare Disease Could Whack Sammy Bull|last=Guart|first=Al|date=March 31, 2002|work=New York Post|access-date=January 28, 2020|archive-date=January 11, 2012|archive-url=https://web.archive.org/web/20120111205022/http://pqasb.pqarchiver.com/nypost/access/112826137.html?dids=112826137:112826137&FMT=ABS&FMTS=ABS:FT&type=current&date=Mar+31%2C+2002&author=Al+Guart&pub=New+York+Post&desc=RARE+DISEASE+COULD+WHACK+SAMMY+BULL%27&pqatl=google|url-status=dead}}</ref>
* [[Jim Hamilton (rugby union)|Jim Hamilton]], Scottish rugby player, discovered he had Graves' disease shortly after retiring from the sport in 2017.<ref>{{cite web|url=https://www.youtube.com/watch?v=yTj3JQEla-A|title=Hamilton talks about his disease on his podcast|website=[[YouTube]]|date=8 June 2017 |url-status=live|archive-url=https://web.archive.org/web/20170908171950/https://www.youtube.com/watch?v=yTj3JQEla-A|archive-date=2017-09-08}}</ref>
* [[Heino]], German folk singer, whose dark sunglasses (worn to hide his symptoms) became part of his trademark look<ref>{{cite web |url=http://www.spiegel.de/international/zeitgeist/german-crooner-heino-makes-comeback-with-hard-rock-album-a-881889.html |title=Crossover Crooner: The Strange Comeback of Germany's Wannabe Johnny Cash |publisher=Spiegel.de |date=2013-02-07 |access-date=2014-07-27 |url-status=live |archive-url=https://web.archive.org/web/20141119060602/http://www.spiegel.de/international/zeitgeist/german-crooner-heino-makes-comeback-with-hard-rock-album-a-881889.html |archive-date=2014-11-19 }}</ref>
* [[Herbert Howells]], British composer; the first person to be treated with radium injections<ref>{{Cite book|title=Herbert Howells|last=Spicer|first=Paul| name-list-style = vanc |publisher=Seren|year=1998|isbn=1-85411-233-3|location=Bridgend|pages=44}}</ref>
* [[Yayoi Kusama]], Japanese artist<ref>{{cite web |url=https://bombmagazine.org/articles/yayoi-kusama |title=Yayoi Kusama by Grady T. Turner |date=January 1, 1999|website=Bomb Magazine|access-date=May 29, 2020}}</ref>
* [[Nadezhda Krupskaya]], Russian Communist and wife of [[Vladimir Lenin]]<ref>{{cite news |url=https://www.rbth.com/arts/2017/05/18/revolutionary-first-lady-the-life-and-struggles-of-lenins-wife_765659 |title=Revolutionary First Lady: the life and struggles of Lenin's wife |newspaper=Russia Beyond |access-date=2018-04-18 |url-status=dead |archive-url=https://web.archive.org/web/20180418230109/https://www.rbth.com/arts/2017/05/18/revolutionary-first-lady-the-life-and-struggles-of-lenins-wife_765659 |archive-date=2018-04-18 }}</ref>
* [[Umm Kulthum]] was an Egyptian singer, songwriter, and film actress active from the 1920s to the 1970s.
* [[Barbara Leigh]], an American former actress and fashion model, now spokeswoman for the National Graves' Disease Foundation<ref>{{cite web |url=http://home.rmci.net/deecee/barbara_leigh.htm |title=Barbara Leigh |publisher=Home.rmci.net |access-date=2013-02-27 |url-status=dead |archive-url=https://archive.today/20120710201715/http://home.rmci.net/deecee/barbara_leigh.htm |archive-date=2012-07-10 }}</ref>
* [[Keiko Masuda]], Japanese singer and one-half of the duo [[Pink Lady (duo)|Pink Lady]].<ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110804-OYTEW53427/ |title=［歌手 増田恵子さん］バセドー病（１）マイク持つ手が震える |publisher=[[Yomiuri Shimbun]] |date=2011-08-04 |access-date=2020-02-01}}</ref><ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110811-OYTEW53431/ |title=［歌手 増田恵子さん］バセドー病（２）同じ病 姉の存在が支えに |publisher=[[Yomiuri Shimbun]] |date=2011-08-11 |access-date=2020-02-01}}</ref><ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110818-OYTEW53435/ |title=［歌手 増田恵子さん］バセドー病（３）ツアー中、甲状腺腫れ上がる |publisher=[[Yomiuri Shimbun]] |date=2011-08-18 |access-date=2020-02-01}}</ref><ref>{{cite web |url=https://yomidr.yomiuri.co.jp/article/20110825-OYTEW53440/ |title=［歌手 増田恵子さん］バセドー病（４）病気公表 無理せず我慢せず |publisher=[[Yomiuri Shimbun]] |date=2011-08-25 |access-date=2020-02-01}}</ref>
* [[Yūko Miyamura]], Japanese voice actress<ref>{{cite web|archive-url=https://web.archive.org/web/20070515220804/http://www3.bigcosmic.com/board/s/board.cgi?id=TSokcs&mode=cal&y=2007&m=5&d=12|archive-date=May 15, 2007|url=http://www3.bigcosmic.com/board/s/board.cgi?id=TSokcs&mode=cal&y=2007&m=5&d=12|title=親子知新|publisher=www3.bigcosmic.com|access-date=December 18, 2017}}</ref>
* [[Christopher Monckton, 3rd Viscount Monckton of Brenchley|Lord Monckton]], former [[UK Independence Party|UKIP]] and [[Conservative Party (UK)|Conservative]] politician; notorious promoter of [[Climate change denial|climate change denial]]<ref>Rupert Murray [http://www.bbc.co.uk/programmes/b00y5j3v "Meet the Climate Sceptics"] {{webarchive|url=https://web.archive.org/web/20131022043959/http://www.bbc.co.uk/programmes/b00y5j3v |date=2013-10-22 }}, ''[[Storyville (TV series)|Storyville]]'', 3 February 2011.</ref><ref>{{cite web |last1=Abraham |first1=John |title=The chief troupier: the follies of Mr Monckton |url=https://theconversation.com/the-chief-troupier-the-follies-of-mr-monckton-1555 |website=[[The Conversation (website)|The Conversation]] |publisher=The Conversation Media Group Ltd |access-date=14 August 2024 |date=22 June 2011 |quote=...in Mr. Monckton’s speeches, he cites study after study which give the impression that either climate change is not happening, or if it is, we don’t need to worry about it.}}</ref>
* [[Sophia Parnok]], Russian poet<ref>{{Cite web | url=https://www.makingqueerhistory.com/articles/2017/4/3/sophia-parnok-russias-sappho | title=Sophia Parnok, Russia's Sappho| date=3 April 2017}}</ref><ref>{{Cite journal | url=https://www.cambridge.org/core/journals/slavic-review/article/sophia-parnok-and-the-writing-of-a-lesbian-poets-life/6BB1085AA4A69E221210F210F1CF7727 |doi = 10.2307/2499528|jstor = 2499528|title = Sophia Parnok and the Writing of a Lesbian Poet's Life|year = 1992|last1 = Burgin|first1 = Diana Lewis|journal = Slavic Review|volume = 51|issue = 2|pages = 214–231| s2cid=163967264 }}</ref><ref>https://www.king.org/event/the-esoterics-parnok-in-that-infinite-moment/{{Dead link|date=November 2021 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
* [[Cecil Spring Rice|Sir Cecil Spring Rice]], British ambassador to the United States during World War I, died suddenly of the disease in 1918.<ref>{{cite news |url=https://www.telegraph.co.uk/history/10088951/This-memorial-is-poetic-justice-for-Sir-Cecil-Spring-Rice.html |title=This memorial is poetic justice for Sir Cecil Spring Rice |date=31 May 2013 |publisher=telegraph.co.uk |access-date=2014-08-25 |url-status=dead |archive-url=https://web.archive.org/web/20140312080447/http://www.telegraph.co.uk/history/10088951/This-memorial-is-poetic-justice-for-Sir-Cecil-Spring-Rice.html |archive-date=2014-03-12 |last1=Simon |first1=Bernard }}</ref>
* [[Daisy Ridley]], British actress<ref>{{cite web | url=https://www.hollywoodreporter.com/lifestyle/lifestyle-news/daisy-ridley-graves-disease-1235966996/ | title=Daisy Ridley Reveals Graves' Disease Diagnosis | website=[[The Hollywood Reporter]] | date=6 August 2024 }}</ref>
* [[Christina Rossetti]], English Victorian-era poet<ref>{{cite web |url=http://www.poetryfoundation.org/bio/christina-rossetti |title=Christina Rossetti |publisher=Poetry Foundation |access-date=2016-09-10 |url-status=live |archive-url=https://web.archive.org/web/20160417025258/http://www.poetryfoundation.org/bio/christina-rossetti |archive-date=2016-04-17 }}</ref>
* [[Maggie Smith|Dame Maggie Smith]], British actress<ref>{{cite news|url=https://www.nytimes.com/1990/03/18/magazine/there-is-nothing-like-this-dame.html|title=There is Nothing Like This Dame|last=Wolf|first=Matt | name-list-style = vanc |newspaper=New York Times|date=March 18, 1990|access-date=2015-10-19|url-status=live|archive-url=https://web.archive.org/web/20160810160402/http://www.nytimes.com/1990/03/18/magazine/there-is-nothing-like-this-dame.html|archive-date=August 10, 2016}}</ref>
* [[Mary Webb]], British novelist and poet<ref>{{cite web |url=http://www.marywebbsociety.co.uk/biography/ |title=Biography |access-date=2015-07-16 |url-status=live |archive-url=https://web.archive.org/web/20150716204649/http://www.marywebbsociety.co.uk/biography/ |archive-date=2015-07-16 }}</ref>
* [[Wendy Williams]], American TV show host<ref>{{cite web|url=https://us.cnn.com/2018/02/21/entertainment/wendy-williams-graves-disease/index.html|title=Wendy Williams announces show hiatus due to Graves' disease|last=Melas|first=Chloe | name-list-style = vanc |date=February 21, 2018|website=CNN|access-date=February 21, 2018}}</ref>
* [[Act Yasukawa]], Japanese professional wrestler<ref>{{cite web|url=https://theovertimer.com/2020/11/act-yasukawa-returns-to-ring-after-five-years-away//|title=Act Yasukawa Returns To Ring After Five Years Away|date=15 November 2020}}</ref>
<!-- NB! - alphabetical order by surname, please – thanks -->
=== Literature ===
* In [[Italo Svevo]]'s novel ''[[Zeno's Conscience]]'', character Ada develops the disease.<ref>{{cite book |last1=Svevo |first1=Italo |title=Zeno's conscience : a novel |year=2003 |publisher=Vintage Books |isbn=0375727760 |pages=315–321 |edition=1st Vintage International}}</ref><ref>{{cite web |last1=Scarponi |first1=Mattia |title=Il morbo di Basedow: lo sfinimento tra Zeno e la realtà |url=https://www.thewisemagazine.it/2017/08/19/morbo-di-basedow-sfinimento-zeno-realta/ |website=theWise Magazine |access-date=25 March 2020 |language=it-IT |date=19 August 2017}}</ref>
* [[Ern Malley]] was an acclaimed Australian poet whose work was not published until after his death from Graves' disease in 1943. However, Malley's existence and entire biography was actually later revealed to be a [[literary hoax]].
==Research==
Agents that act as antagonists at thyroid stimulating hormone receptors are under investigation as a possible treatment for Graves' disease.<ref>{{cite web|title=Thyroid|url=http://www.mayo.edu/research/departments-divisions/department-internal-medicine/division-endocrinology-diabetes-metabolism-nutrition/thyroid|website=Mayo Clinic|access-date=1 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161104001231/http://www.mayo.edu/research/departments-divisions/department-internal-medicine/division-endocrinology-diabetes-metabolism-nutrition/thyroid|archive-date=4 November 2016}}</ref>
== References ==
{{Reflist}}
== External links ==
* {{cite web | url = https://ghr.nlm.nih.gov/condition/graves-disease | publisher = U.S. National Library of Medicine | work = Genetics Home Reference | title = Graves' disease }}
* https://www.ncbi.nlm.nih.gov/gene/?term=graves about graves on ncbi
{{Medical condition classification and resources
| Curlie = Health/Conditions_and_Diseases/Endocrine_Disorders/Thyroid/Hyperthyroidism/Graves%27_Disease/
| ICD10 = {{ICD10|E|05|0|e|00}}
| ICD9 = {{ICD9|242.0}}
| ICDO =
| DiseasesDB = 5419
| OMIM = 275000
| MedlinePlus = 000358
| eMedicineSubj = med
| eMedicineTopic = 929
| eMedicine_mult = {{eMedicine2|ped|899}}
| MeshID = D006111
| SNOMED CT = 353295004
|ICD11={{ICD11|5A02.0}}|ICD10CM={{ICD10CM|E05.0}}}}
{{Thyroid disease}}
{{Autoimmune diseases}}
{{Authority control}}
{{DEFAULTSORT:Graves disease}}
[[Category:Autoimmune diseases]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Thyroid disease]]' |
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==Signs and symptoms==
{{Main|Signs and symptoms of Graves' disease}}
-[[Image:HyperaldosteronismSymptoms.jpeg|thumb|upright=1.3|Graves disease symptoms]]
-The signs and symptoms of Graves disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being [[Graves ophthalmopathy]], [[goiter]], and [[pretibial myxedema]] (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly [[insomnia]], hand [[tremor]], [[hyperactivity]], hair loss, excessive [[sweating]], [[oligomenorrhea]], itching, [[heat intolerance]], [[weight loss]] despite [[increased appetite]], [[diarrhea]], frequent [[defecation]], [[palpitation]]s, [[muscle weakness|periodic partial muscle weakness or paralysis]] in those especially of Asian descent,<ref>{{cite book|last1=N. Burrow|first1=Gerard|last2=H. Oppenheimer|first2=Jack|last3=Volpé|first3=Robert|name-list-style=vanc|title=Thyroid function & disease|date=1989|publisher=W.B. Saunders |isbn=0721621902|url-access=registration|url=https://archive.org/details/thyroidfunctiond00burr}}</ref> and skin warmth and moistness.<ref name=agabegi2nd157>page 157 in:{{cite book | first1 = Elizabeth D | last1 = Agabegi | last2 = Agabegi | first2 = Steven S. | name-list-style = vanc | title = Step-Up to Medicine (Step-Up Series) | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2008 | isbn = 978-0-7817-7153-5 | url-access = registration | url = https://archive.org/details/stepuptomedicine0000agab }}</ref> Further signs that may be seen on [[physical examination]] are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, [[lid lag]], excessive [[tears|lacrimation]] due to Graves' ophthalmopathy, [[Heart arrhythmia|arrhythmia]]s of the heart, such as [[sinus tachycardia]], [[atrial fibrillation]], and [[premature ventricular contraction]]s, and [[hypertension]].<ref name=agabegi2nd157/><ref>{{cite journal | vauthors = Bunevicius R, Prange AJ | title = Psychiatric manifestations of Graves hyperthyroidism: pathophysiology and treatment options | journal = CNS Drugs | volume = 20 | issue = 11 | pages = 897–909 | year = 2006 | pmid = 17044727 | doi = 10.2165/00023210-200620110-00003 | s2cid = 20003511 }}</ref>
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1 => 'The signs and symptoms of Graves disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being [[Graves ophthalmopathy]], [[goiter]], and [[pretibial myxedema]] (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly [[insomnia]], hand [[tremor]], [[hyperactivity]], hair loss, excessive [[sweating]], [[oligomenorrhea]], itching, [[heat intolerance]], [[weight loss]] despite [[increased appetite]], [[diarrhea]], frequent [[defecation]], [[palpitation]]s, [[muscle weakness|periodic partial muscle weakness or paralysis]] in those especially of Asian descent,<ref>{{cite book|last1=N. Burrow|first1=Gerard|last2=H. Oppenheimer|first2=Jack|last3=Volpé|first3=Robert|name-list-style=vanc|title=Thyroid function & disease|date=1989|publisher=W.B. Saunders |isbn=0721621902|url-access=registration|url=https://archive.org/details/thyroidfunctiond00burr}}</ref> and skin warmth and moistness.<ref name=agabegi2nd157>page 157 in:{{cite book | first1 = Elizabeth D | last1 = Agabegi | last2 = Agabegi | first2 = Steven S. | name-list-style = vanc | title = Step-Up to Medicine (Step-Up Series) | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2008 | isbn = 978-0-7817-7153-5 | url-access = registration | url = https://archive.org/details/stepuptomedicine0000agab }}</ref> Further signs that may be seen on [[physical examination]] are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, [[lid lag]], excessive [[tears|lacrimation]] due to Graves' ophthalmopathy, [[Heart arrhythmia|arrhythmia]]s of the heart, such as [[sinus tachycardia]], [[atrial fibrillation]], and [[premature ventricular contraction]]s, and [[hypertension]].<ref name=agabegi2nd157/><ref>{{cite journal | vauthors = Bunevicius R, Prange AJ | title = Psychiatric manifestations of Graves hyperthyroidism: pathophysiology and treatment options | journal = CNS Drugs | volume = 20 | issue = 11 | pages = 897–909 | year = 2006 | pmid = 17044727 | doi = 10.2165/00023210-200620110-00003 | s2cid = 20003511 }}</ref>'
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Parsed HTML source of the new revision (new_html) | '<div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Autoimmune endocrine disease</div>
<div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Medical condition</div><style data-mw-deduplicate="TemplateStyles:r1237879389">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}body.skin-minerva .mw-parser-output .infobox-header,body.skin-minerva .mw-parser-output .infobox-subheader,body.skin-minerva .mw-parser-output .infobox-above,body.skin-minerva .mw-parser-output .infobox-title,body.skin-minerva .mw-parser-output .infobox-image,body.skin-minerva .mw-parser-output .infobox-full-data,body.skin-minerva .mw-parser-output .infobox-below{text-align:center}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox ib-medical-condition"><tbody><tr><th colspan="2" class="infobox-above" style="background:#ccc">Graves' disease</th></tr><tr><th scope="row" class="infobox-label">Other names</th><td class="infobox-data">Toxic diffuse goiter, <br />Flajani–Basedow–Graves disease</td></tr><tr style="background-color: #f8f9fa;"><td colspan="2" class="infobox-full-data"><span class="mw-default-size" typeof="mw:File/Frameless"><a href="/wiki/File:Proptosis_and_lid_retraction_from_Graves%27_Disease.jpg" class="mw-file-description"><img src="/media/wikipedia/commons/thumb/8/8f/Proptosis_and_lid_retraction_from_Graves%27_Disease.jpg/220px-Proptosis_and_lid_retraction_from_Graves%27_Disease.jpg" decoding="async" width="220" height="143" class="mw-file-element" srcset="/media/wikipedia/commons/8/8f/Proptosis_and_lid_retraction_from_Graves%27_Disease.jpg 1.5x" data-file-width="300" data-file-height="195" /></a></span></td></tr><tr><td colspan="2" class="infobox-full-data">The classic finding of <a href="/wiki/Exophthalmos" title="Exophthalmos">exophthalmos</a> and lid retraction in Graves' disease</td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_specialty" title="Medical specialty">Specialty</a></th><td class="infobox-data"><a href="/wiki/Endocrinology" title="Endocrinology">Endocrinology</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Signs_and_symptoms" title="Signs and symptoms">Symptoms</a></th><td class="infobox-data"><a href="/wiki/Goitre" title="Goitre">Enlarged thyroid</a>, <a href="/wiki/Irritability" title="Irritability">irritability</a>, <a href="/wiki/Myopathy" title="Myopathy">muscle weakness</a>, <a href="/wiki/Insomnia" title="Insomnia">sleeping problems</a>, <a href="/wiki/Tachycardia" title="Tachycardia">fast heartbeat</a>, <a href="/wiki/Weight_loss" title="Weight loss">weight loss</a>, <a href="/wiki/Heat_intolerance" title="Heat intolerance">poor tolerance of heat</a>,<sup id="cite_ref-NIH2012_1-0" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Anxiety" title="Anxiety">anxiety</a>, tremor of hands or fingers, warm and moist skin, increased <a href="/wiki/Perspiration" title="Perspiration">perspiration</a>, <a href="/wiki/Goiter" class="mw-redirect" title="Goiter">goiter</a>, changes in menstrual cycle, easy bruising, <a href="/wiki/Erectile_dysfunction" title="Erectile dysfunction">erectile dysfunction</a>, reduced libido, frequent bowel movements, bulging eyes (<a href="/wiki/Graves%27_ophthalmopathy" title="Graves' ophthalmopathy">Graves' ophthalmopathy</a>), thick red skin on shins or the top of foot (<a href="/wiki/Pretibial_myxedema" title="Pretibial myxedema">pretibial myxedema</a>)<sup id="cite_ref-AR_2-0" class="reference"><a href="#cite_note-AR-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Complication_(medicine)" title="Complication (medicine)">Complications</a></th><td class="infobox-data"><a href="/wiki/Graves%27_ophthalmopathy" title="Graves' ophthalmopathy">Graves' ophthalmopathy</a><sup id="cite_ref-NIH2012_1-1" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label">Causes</th><td class="infobox-data">Unknown<sup id="cite_ref-Men2014_3-0" class="reference"><a href="#cite_note-Men2014-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Risk_factor" title="Risk factor">Risk factors</a></th><td class="infobox-data">Family history, other <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune diseases</a><sup id="cite_ref-NIH2012_1-2" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_diagnosis" title="Medical diagnosis">Diagnostic method</a></th><td class="infobox-data">Blood tests, <a href="/wiki/Radioiodine" class="mw-redirect" title="Radioiodine">radioiodine</a> uptake<sup id="cite_ref-NIH2012_1-3" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-NEJM2008_4-0" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label">Treatment</th><td class="infobox-data"><a href="/wiki/Radioiodine_therapy" class="mw-redirect" title="Radioiodine therapy">Radioiodine therapy</a>, <a href="/wiki/Antithyroid_agents" class="mw-redirect" title="Antithyroid agents">antithyroid</a> and <a href="/wiki/Beta_blocker" title="Beta blocker">beta blocker</a> medications, <a href="/wiki/Thyroidectomy" title="Thyroidectomy">thyroid surgery</a><sup id="cite_ref-NIH2012_1-4" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label">Frequency</th><td class="infobox-data">0.5% (males), 3% (females)<sup id="cite_ref-Hen2015_5-0" class="reference"><a href="#cite_note-Hen2015-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup></td></tr></tbody></table>
<p><b>Graves' disease</b>, also known as <b>toxic diffuse goiter</b> or <b>Basedow’s disease</b>, is an <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune disease</a> that affects the <a href="/wiki/Thyroid" title="Thyroid">thyroid</a>.<sup id="cite_ref-NIH2012_1-5" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> It frequently results in and is the most common cause of <a href="/wiki/Hyperthyroidism" title="Hyperthyroidism">hyperthyroidism</a>.<sup id="cite_ref-Hen2015_5-1" class="reference"><a href="#cite_note-Hen2015-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> It also often results in an <a href="/wiki/Goitre" title="Goitre">enlarged thyroid</a>.<sup id="cite_ref-NIH2012_1-6" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Signs and symptoms of hyperthyroidism may include <a href="/wiki/Irritability" title="Irritability">irritability</a>, <a href="/wiki/Myopathy" title="Myopathy">muscle weakness</a>, <a href="/wiki/Insomnia" title="Insomnia">sleeping problems</a>, a <a href="/wiki/Tachycardia" title="Tachycardia">fast heartbeat</a>, <a href="/wiki/Heat_intolerance" title="Heat intolerance">poor tolerance of heat</a>, <a href="/wiki/Diarrhea" title="Diarrhea">diarrhea</a> and <a href="/wiki/Weight_loss#unintentional" title="Weight loss">unintentional weight loss</a>.<sup id="cite_ref-NIH2012_1-7" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Other symptoms may include thickening of the skin on the shins, known as <a href="/wiki/Pretibial_myxedema" title="Pretibial myxedema">pretibial myxedema</a>, and <a href="/wiki/Exophthalmos" title="Exophthalmos">eye bulging</a>, a condition caused by <a href="/wiki/Graves%27_ophthalmopathy" title="Graves' ophthalmopathy">Graves' ophthalmopathy</a>.<sup id="cite_ref-NIH2012_1-8" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> About 25 to 30% of people with the condition develop eye problems.<sup id="cite_ref-NIH2012_1-9" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-NEJM2008_4-1" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup>
</p><p>The exact cause of the disease is unclear, but symptoms are a result of antibodies binding to receptors on the thyroid causing over-expression of thyroid hormone.<sup id="cite_ref-Men2014_3-1" class="reference"><a href="#cite_note-Men2014-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Persons are more likely to be affected if they have a family member with the disease.<sup id="cite_ref-NIH2012_1-10" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> If one <a href="/wiki/Identical_twin" class="mw-redirect" title="Identical twin">monozygotic twin</a> is affected, a 30% chance exists that the other twin will also have the disease.<sup id="cite_ref-Nik2012_6-0" class="reference"><a href="#cite_note-Nik2012-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> The onset of disease may be triggered by physical or emotional stress, infection, or <a href="/wiki/Childbirth" title="Childbirth">giving birth</a>.<sup id="cite_ref-NEJM2008_4-2" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Those with other autoimmune diseases, such as <a href="/wiki/Type_1_diabetes" title="Type 1 diabetes">type 1 diabetes</a> and <a href="/wiki/Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a>, are more likely to be affected.<sup id="cite_ref-NIH2012_1-11" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Smoking increases the risk of disease and may worsen eye problems.<sup id="cite_ref-NIH2012_1-12" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> The disorder results from an <a href="/wiki/Antibody" title="Antibody">antibody</a>, called thyroid-stimulating immunoglobulin (TSI), that has a similar effect to <a href="/wiki/Thyroid_stimulating_hormone" class="mw-redirect" title="Thyroid stimulating hormone">thyroid stimulating hormone</a> (TSH).<sup id="cite_ref-NIH2012_1-13" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> These TSI antibodies cause the <a href="/wiki/Thyroid_gland" class="mw-redirect" title="Thyroid gland">thyroid gland</a> to produce excess <a href="/wiki/Thyroid_hormones" title="Thyroid hormones">thyroid hormones</a>.<sup id="cite_ref-NIH2012_1-14" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> The diagnosis may be suspected based on symptoms and confirmed with blood tests and <a href="/wiki/Radioiodine" class="mw-redirect" title="Radioiodine">radioiodine</a> uptake.<sup id="cite_ref-NIH2012_1-15" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-NEJM2008_4-3" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Typically, blood tests show a raised <a href="/wiki/Triiodothyronine" title="Triiodothyronine">T<sub>3</sub></a> and <a href="/wiki/Thyroxine" class="mw-redirect" title="Thyroxine">T<sub>4</sub></a>, low TSH, increased radioiodine uptake in all areas of the thyroid, and TSI antibodies.<sup id="cite_ref-NEJM2008_4-4" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup>
</p><p>The three treatment options are <a href="/wiki/Radioiodine_therapy" class="mw-redirect" title="Radioiodine therapy">radioiodine therapy</a>, medications, and <a href="/wiki/Thyroidectomy" title="Thyroidectomy">thyroid surgery</a>.<sup id="cite_ref-NIH2012_1-16" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Radioiodine therapy involves taking <a href="/wiki/Iodine-131" title="Iodine-131">iodine-131</a> by mouth, which is then concentrated in the thyroid and destroys it over weeks to months.<sup id="cite_ref-NIH2012_1-17" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> The resulting <a href="/wiki/Hypothyroidism" title="Hypothyroidism">hypothyroidism</a> is treated with <a href="/wiki/Thyroid_hormone#Medical_use" class="mw-redirect" title="Thyroid hormone">synthetic thyroid hormones</a>.<sup id="cite_ref-NIH2012_1-18" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Medications such as <a href="/wiki/Beta_blockers" class="mw-redirect" title="Beta blockers">beta blockers</a> may control some of the symptoms, and <a href="/wiki/Anti-thyroid_medication" class="mw-redirect" title="Anti-thyroid medication">antithyroid medications</a> such as <a href="/wiki/Methimazole" class="mw-redirect" title="Methimazole">methimazole</a> may temporarily help people, while other treatments are having effect.<sup id="cite_ref-NIH2012_1-19" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Surgery to remove the thyroid is another option.<sup id="cite_ref-NIH2012_1-20" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Eye problems may require additional treatments.<sup id="cite_ref-NIH2012_1-21" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup>
</p><p>Graves disease develops in about 0.5% of males and 3.0% of females.<sup id="cite_ref-Hen2015_5-2" class="reference"><a href="#cite_note-Hen2015-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> It occurs about 7.5 times more often in women than in men.<sup id="cite_ref-NIH2012_1-22" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Often, it starts between the ages of 40 and 60, but can begin at any age.<sup id="cite_ref-Nik2012_6-1" class="reference"><a href="#cite_note-Nik2012-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).<sup id="cite_ref-NIH2012_1-23" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-NEJM2008_4-5" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> The condition is named after Irish surgeon <a href="/wiki/Robert_James_Graves" title="Robert James Graves">Robert Graves</a>, who described it in 1835.<sup id="cite_ref-Nik2012_6-2" class="reference"><a href="#cite_note-Nik2012-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> A number of prior descriptions also exist.<sup id="cite_ref-Nik2012_6-3" class="reference"><a href="#cite_note-Nik2012-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup>
</p>
<div id="toc" class="toc" role="navigation" aria-labelledby="mw-toc-heading"><input type="checkbox" role="button" id="toctogglecheckbox" class="toctogglecheckbox" style="display:none" /><div class="toctitle" lang="en" dir="ltr"><h2 id="mw-toc-heading">Contents</h2><span class="toctogglespan"><label class="toctogglelabel" for="toctogglecheckbox"></label></span></div>
<ul>
<li class="toclevel-1 tocsection-1"><a href="#Signs_and_symptoms"><span class="tocnumber">1</span> <span class="toctext">Signs and symptoms</span></a></li>
<li class="toclevel-1 tocsection-2"><a href="#Cause"><span class="tocnumber">2</span> <span class="toctext">Cause</span></a>
<ul>
<li class="toclevel-2 tocsection-3"><a href="#Genetics"><span class="tocnumber">2.1</span> <span class="toctext">Genetics</span></a></li>
<li class="toclevel-2 tocsection-4"><a href="#Infectious_trigger"><span class="tocnumber">2.2</span> <span class="toctext">Infectious trigger</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-5"><a href="#Mechanism"><span class="tocnumber">3</span> <span class="toctext">Mechanism</span></a>
<ul>
<li class="toclevel-2 tocsection-6"><a href="#Pathophysiology"><span class="tocnumber">3.1</span> <span class="toctext">Pathophysiology</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-7"><a href="#Diagnosis"><span class="tocnumber">4</span> <span class="toctext">Diagnosis</span></a>
<ul>
<li class="toclevel-2 tocsection-8"><a href="#Eye_disease"><span class="tocnumber">4.1</span> <span class="toctext">Eye disease</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-9"><a href="#Management"><span class="tocnumber">5</span> <span class="toctext">Management</span></a>
<ul>
<li class="toclevel-2 tocsection-10"><a href="#Antithyroid_drugs"><span class="tocnumber">5.1</span> <span class="toctext">Antithyroid drugs</span></a></li>
<li class="toclevel-2 tocsection-11"><a href="#Radioiodine"><span class="tocnumber">5.2</span> <span class="toctext">Radioiodine</span></a></li>
<li class="toclevel-2 tocsection-12"><a href="#Surgery"><span class="tocnumber">5.3</span> <span class="toctext">Surgery</span></a></li>
<li class="toclevel-2 tocsection-13"><a href="#Eyes"><span class="tocnumber">5.4</span> <span class="toctext">Eyes</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-14"><a href="#Prognosis"><span class="tocnumber">6</span> <span class="toctext">Prognosis</span></a></li>
<li class="toclevel-1 tocsection-15"><a href="#Epidemiology"><span class="tocnumber">7</span> <span class="toctext">Epidemiology</span></a></li>
<li class="toclevel-1 tocsection-16"><a href="#History"><span class="tocnumber">8</span> <span class="toctext">History</span></a></li>
<li class="toclevel-1 tocsection-17"><a href="#Society_and_culture"><span class="tocnumber">9</span> <span class="toctext">Society and culture</span></a>
<ul>
<li class="toclevel-2 tocsection-18"><a href="#Notable_cases"><span class="tocnumber">9.1</span> <span class="toctext">Notable cases</span></a></li>
<li class="toclevel-2 tocsection-19"><a href="#Literature"><span class="tocnumber">9.2</span> <span class="toctext">Literature</span></a></li>
</ul>
</li>
<li class="toclevel-1 tocsection-20"><a href="#Research"><span class="tocnumber">10</span> <span class="toctext">Research</span></a></li>
<li class="toclevel-1 tocsection-21"><a href="#References"><span class="tocnumber">11</span> <span class="toctext">References</span></a></li>
<li class="toclevel-1 tocsection-22"><a href="#External_links"><span class="tocnumber">12</span> <span class="toctext">External links</span></a></li>
</ul>
</div>
<div class="mw-heading mw-heading2"><h2 id="Signs_and_symptoms">Signs and symptoms</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=1" title="Edit section: Signs and symptoms"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
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<div class="mw-heading mw-heading2"><h2 id="Cause">Cause</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=2" title="Edit section: Cause"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>The exact cause is unclear, but it is believed to involve a combination of genetic and environmental factors.<sup id="cite_ref-Men2014_3-2" class="reference"><a href="#cite_note-Men2014-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> While a theoretical mechanism occurs by which exposure to severe stressors and high levels of subsequent distress such as <a href="/wiki/Post-traumatic_stress_disorder" title="Post-traumatic stress disorder">post-traumatic stress disorder</a> could increase the risk of immune disease and cause an aggravation of the autoimmune response that leads to Graves disease, more robust clinical data are needed for a firm conclusion.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Genetics">Genetics</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=3" title="Edit section: Genetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>A <a href="/wiki/Genetics" title="Genetics">genetic</a> predisposition for Graves' disease is seen, with some people more prone to develop <a href="/wiki/Thyrotropin_receptor" title="Thyrotropin receptor">TSH receptor</a>-activating antibodies due to a genetic cause. <a href="/wiki/Human_leukocyte_antigen" title="Human leukocyte antigen">Human leukocyte antigen</a> DR (especially DR3) appears to play a role.<sup id="cite_ref-EndocrReview1993_8-0" class="reference"><a href="#cite_note-EndocrReview1993-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> To date, no clear genetic defect has been found to point to a <a href="/wiki/Monogenic_(genetics)" class="mw-redirect" title="Monogenic (genetics)">single-gene</a> cause.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup>
</p><p>Genes believed to be involved include those for <a href="/wiki/Thyroglobulin" title="Thyroglobulin">thyroglobulin</a>, <a href="/wiki/Thyrotropin_receptor" title="Thyrotropin receptor">thyrotropin receptor</a>, <a href="/wiki/Protein_tyrosine_phosphatase" title="Protein tyrosine phosphatase">protein tyrosine phosphatase</a> nonreceptor type 22 (<i><a href="/wiki/PTPN22" title="PTPN22">PTPN22</a></i>), and <a href="/wiki/Cytotoxic_T-lymphocyte%E2%80%93associated_antigen_4" class="mw-redirect" title="Cytotoxic T-lymphocyte–associated antigen 4">cytotoxic T-lymphocyte–associated antigen 4</a>, among others.<sup id="cite_ref-NEJM2016_9-0" class="reference"><a href="#cite_note-NEJM2016-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Infectious_trigger">Infectious trigger</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=4" title="Edit section: Infectious trigger"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Since Graves disease is an autoimmune disease that appears suddenly, often later in life, a <a href="/wiki/Virus" title="Virus">viral</a> or <a href="/wiki/Bacteria" title="Bacteria">bacterial</a> infection may trigger antibodies, which cross-react with the human TSH receptor, a phenomenon known as <a href="/wiki/Antigenic_mimicry" class="mw-redirect" title="Antigenic mimicry">antigenic mimicry</a>.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup>
</p><p>The bacterium <i><a href="/wiki/Yersinia_enterocolitica" title="Yersinia enterocolitica">Yersinia enterocolitica</a></i> bears structural similarity with the human thyrotropin receptor<sup id="cite_ref-EndocrReview1993_8-1" class="reference"><a href="#cite_note-EndocrReview1993-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> and was hypothesized to contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup>
In the 1990s, <i>Y. enterocolitica</i> was suggested to be possibly <a href="/wiki/Association_(statistics)" class="mw-redirect" title="Association (statistics)">associated</a> with Graves' disease.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup>
More recently, the role for <i>Y. enterocolitica</i> has been disputed.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup>
</p><p><a href="/wiki/Epstein%E2%80%93Barr_virus" title="Epstein–Barr virus">Epstein–Barr virus</a> is another potential trigger.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="Mechanism">Mechanism</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=5" title="Edit section: Mechanism"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Thyroid-stimulating immunoglobulins recognize and bind to the TSH receptor, which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3). Thyroxine receptors in the pituitary gland are activated by the surplus hormone, suppressing additional release of TSH in a negative feedback loop. The result is very high levels of circulating thyroid hormones and a low TSH level.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (July 2022)">citation needed</span></a></i>]</sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Pathophysiology">Pathophysiology</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=6" title="Edit section: Pathophysiology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Histopathology_of_Graves%27_disease_-_medium_mag.jpg" class="mw-file-description"><img src="/media/wikipedia/commons/thumb/2/2b/Histopathology_of_Graves%27_disease_-_medium_mag.jpg/220px-Histopathology_of_Graves%27_disease_-_medium_mag.jpg" decoding="async" width="220" height="150" class="mw-file-element" srcset="/media/wikipedia/commons/thumb/2/2b/Histopathology_of_Graves%27_disease_-_medium_mag.jpg/330px-Histopathology_of_Graves%27_disease_-_medium_mag.jpg 1.5x, /media/wikipedia/commons/thumb/2/2b/Histopathology_of_Graves%27_disease_-_medium_mag.jpg/440px-Histopathology_of_Graves%27_disease_-_medium_mag.jpg 2x" data-file-width="510" data-file-height="348" /></a><figcaption>Histopathology of a case of Grave's disease. It shows marked hyperplasia of <a href="/wiki/Thyroid_follicular_cell" title="Thyroid follicular cell">thyroid follicular cells</a>, generally more so than <a href="/wiki/Toxic_multinodular_goitre" title="Toxic multinodular goitre">toxic multinodular goitre</a>, forming papillae into the thyroid follicles, and with scalloping of the peripheral colloid.</figcaption></figure>
<p>Graves' disease is an <a href="/wiki/Autoimmunity" title="Autoimmunity">autoimmune</a> disorder, in which the body produces <a href="/wiki/Antibody" title="Antibody">antibodies</a> that are specific to a <a href="/wiki/Self-protein" title="Self-protein">self-protein</a> - the receptor for thyroid-stimulating hormone. (Antibodies to thyroglobulin and to the <a href="/wiki/Thyroid_hormone" class="mw-redirect" title="Thyroid hormone">thyroid hormones</a> T3 and T4 may also be produced.)
</p><p>These antibodies cause hyperthyroidism because they bind to the TSHr and <a href="/wiki/Chronic_(medicine)" class="mw-redirect" title="Chronic (medicine)">chronically</a> stimulate it. The TSHr is expressed on the <a href="/wiki/Thyroid_follicular_cell" title="Thyroid follicular cell">thyroid follicular cells</a> of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4. This, in turn, causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.
</p><p>The infiltrative exophthalmos frequently encountered has been explained by postulating that the thyroid gland and the extraocular muscles share a common antigen, which is recognized by the antibodies. Antibodies binding to the extraocular muscles would cause swelling behind the eyeball.
</p><p>The "orange peel" skin has been explained by the infiltration of antibodies under the skin, causing an inflammatory reaction and subsequent fibrous plaques.
</p><p><b>The three types of autoantibodies to the TSH receptor are:</b>
</p>
<ol><li><b>Thyroid stimulating immunoglobulins:</b> these antibodies (mainly IgG) act as long-acting thyroid stimulants, activating the cells through a slower and more drawn out process compared to TSH, leading to an elevated production of thyroid hormone.</li>
<li><b>Thyroid growth immunoglobulins:</b> these antibodies bind directly to the TSH receptor and have been implicated in the growth of thyroid follicles.</li>
<li><b>Thyrotrophin binding-inhibiting immunoglobulins:</b> these antibodies inhibit the normal union of TSH with its receptor.
<ul><li>Some actually act as if TSH itself is binding to its receptor, thus inducing thyroid function.</li>
<li>Other types may not stimulate the thyroid gland, but <u>prevent</u> TSI and TSH from binding to and stimulating the receptor.</li></ul></li></ol>
<p>Another effect of hyperthyroidism is bone loss from osteoporosis, caused by an increased excretion of calcium and phosphorus in the urine and stool. The effects can be minimized if the hyperthyroidism is treated early. <a href="/wiki/Thyrotoxicosis" class="mw-redirect" title="Thyrotoxicosis">Thyrotoxicosis</a> can also augment calcium levels in the blood by as much as 25%. This can cause stomach upset, excessive urination, and impaired kidney function.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="Diagnosis">Diagnosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=7" title="Edit section: Diagnosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Graves disease may present clinically with one or more of these characteristic signs:<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup>
</p>
<ul><li>Rapid heartbeat (80%)</li>
<li>Diffuse palpable goiter with audible <a href="/wiki/Bruit" title="Bruit">bruit</a> (70%)</li>
<li>Tremor (40%)</li>
<li><a href="/wiki/Exophthalmos" title="Exophthalmos">Exophthalmos</a> (protuberance of one or both eyes), periorbital edema (25%)</li>
<li>Fatigue (70%), weight loss (60%) with increased appetite in young people and poor appetite in the elderly, and other symptoms of hyperthyroidism/<a href="/wiki/Thyrotoxicosis" class="mw-redirect" title="Thyrotoxicosis">thyrotoxicosis</a></li>
<li>Heat intolerance (55%)</li>
<li>Tremulousness (55%)</li>
<li>Palpitations (50%)</li></ul>
<p>Two signs are truly diagnostic of Graves' disease (i.e., not seen in other hyperthyroid conditions): exophthalmos and non-pitting edema (<a href="/wiki/Pretibial_myxedema" title="Pretibial myxedema">pretibial myxedema</a>). Goiter is an enlarged thyroid gland and is of the diffuse type (i.e., spread throughout the gland). Diffuse goiter may be seen with other causes of hyperthyroidism, although Graves' disease is the most common cause of diffuse goiter. A large goiter will be visible to the naked eye, but a small one (mild enlargement of the gland) may be detectable only by physical examination. Occasionally, goiter is not clinically detectable, but may be seen only with <a href="/wiki/Computed_tomography" class="mw-redirect" title="Computed tomography">computed tomography</a> or <a href="/wiki/Ultrasound" title="Ultrasound">ultrasound</a> examination of the thyroid.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup> Another sign of Graves' disease is hyperthyroidism, that is, overproduction of the thyroid hormones T3 and T4. Normal thyroid levels are also seen, and occasionally also hypothyroidism, which may assist in causing goiter (though it is not the cause of the Graves' disease). Hyperthyroidism in Graves' disease is confirmed, as with any other cause of hyperthyroidism, by measuring elevated blood levels of free (unbound) T3 and T4.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup>
</p><p>Other useful laboratory measurements in Graves disease include thyroid-stimulating hormone (TSH, usually undetectable in Graves disease due to <a href="/wiki/Negative_feedback" title="Negative feedback">negative feedback</a> from the elevated T3 and T4), and protein-bound <a href="/wiki/Iodine" title="Iodine">iodine</a> (elevated). <a href="/wiki/Serology" title="Serology">Serologically</a> detected thyroid-stimulating antibodies, radioactive iodine uptake, or thyroid <a href="/wiki/Doppler_ultrasonography" title="Doppler ultrasonography">ultrasound with Doppler</a> all can independently confirm a diagnosis of Graves disease.
</p><p><a href="/wiki/Biopsy" title="Biopsy">Biopsy</a> to obtain histiological testing is not normally required, but may be obtained if thyroidectomy is performed.
</p><p>The goiter in Graves disease is often not nodular, but <a href="/wiki/Thyroid_nodule" title="Thyroid nodule">thyroid nodules</a> are also common.<sup id="cite_ref-pmid_9709909_16-0" class="reference"><a href="#cite_note-pmid_9709909-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> Differentiating common forms of hyperthyroidism such as Graves' disease, single <a href="/wiki/Thyroid_adenoma" title="Thyroid adenoma">thyroid adenoma</a>, and <a href="/wiki/Toxic_multinodular_goiter" class="mw-redirect" title="Toxic multinodular goiter">toxic multinodular goiter</a> is important to determine proper treatment.<sup id="cite_ref-pmid_9709909_16-1" class="reference"><a href="#cite_note-pmid_9709909-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> The <a href="/wiki/Toxic_multinodular_goitre#Differentiation_and_terminology_among_types_of_goiter" title="Toxic multinodular goitre">differentiation among these entities has advanced</a>, as imaging and biochemical tests have improved. Measuring TSH-receptor antibodies with the h-TBII assay has been proven efficient and was the most practical approach found in one study.<sup id="cite_ref-pmid_15127319_17-0" class="reference"><a href="#cite_note-pmid_15127319-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Eye_disease">Eye disease</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=8" title="Edit section: Eye disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Further information: <a href="/wiki/Graves_ophthalmopathy" class="mw-redirect" title="Graves ophthalmopathy">Graves ophthalmopathy</a></div>
<p>Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease (TED), is the most common extrathyroidal manifestation of Graves' disease. It is a form of <a href="/wiki/Idiopathic_orbital_inflammatory_disease" title="Idiopathic orbital inflammatory disease">idiopathic lymphocytic orbital inflammation</a>, and although its pathogenesis is not completely understood, autoimmune activation of orbital <a href="/wiki/Fibroblast" title="Fibroblast">fibroblasts</a>, which in TAO express the <a href="/wiki/Thyrotropin_receptor" title="Thyrotropin receptor">TSH receptor</a>, is thought to play a central role.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup>
</p><p><a href="/wiki/Hypertrophy" title="Hypertrophy">Hypertrophy</a> of the extraocular muscles, <a href="/wiki/Adipogenesis" title="Adipogenesis">adipogenesis</a>, and deposition of nonsulfated <a href="/wiki/Glycosaminoglycan" title="Glycosaminoglycan">glycosaminoglycans</a> and hyaluronate, causes expansion of the orbital fat and muscle compartments, which within the confines of the bony orbit may lead to <a href="/wiki/Optic_neuropathy" title="Optic neuropathy">dysthyroid optic neuropathy</a>, increased <a href="/wiki/Glaucoma" title="Glaucoma">intraocular pressures</a>, proptosis, venous congestion leading to chemosis and periorbital edema, and progressive remodeling of the orbital walls.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> Other distinctive features of TAO include lid retraction, restrictive myopathy, superior limbic keratoconjunctivitis, and <a href="/wiki/Exposure_keratopathy" title="Exposure keratopathy">exposure keratopathy</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup>
</p><p>Severity of eye disease may be classified by the mnemonic: "NO SPECS":<sup id="cite_ref-pmid15310608_22-0" class="reference"><a href="#cite_note-pmid15310608-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup>
</p>
<ul><li>Class 0: No signs or symptoms</li>
<li>Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)</li>
<li>Class 2: Soft tissue involvement (<a href="/wiki/Oedema" class="mw-redirect" title="Oedema">oedema</a> of <a href="/wiki/Conjunctiva" title="Conjunctiva">conjunctivae</a> and lids, conjunctival injection, etc.)</li>
<li>Class 3: <a href="/wiki/Proptosis" class="mw-redirect" title="Proptosis">Proptosis</a></li>
<li>Class 4: <a href="/wiki/Extraocular_muscle" class="mw-redirect" title="Extraocular muscle">Extraocular muscle</a> involvement (usually with <a href="/wiki/Diplopia" title="Diplopia">diplopia</a>)</li>
<li>Class 5: Corneal involvement (primarily due to <a href="/wiki/Lagophthalmos" title="Lagophthalmos">lagophthalmos</a>)</li>
<li>Class 6: Sight loss (due to optic nerve involvement)</li></ul>
<p>Typically, the natural history of TAO follows Rundle's curve, which describes a rapid worsening during an initial phase, up to a peak of maximum severity, and then improvement to a static plateau without, however, resolving back to a normal condition.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="Management">Management</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=9" title="Edit section: Management"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Treatment of Graves disease includes <a href="/wiki/Antithyroid_agents" class="mw-redirect" title="Antithyroid agents">antithyroid drugs</a> that reduce the production of thyroid hormone, <a href="/wiki/Radioiodine" class="mw-redirect" title="Radioiodine">radioiodine</a> (radioactive iodine <a href="/wiki/I-131" class="mw-redirect" title="I-131">I-131</a>) and <a href="/wiki/Thyroidectomy" title="Thyroidectomy">thyroidectomy</a> (surgical excision of the gland). As operating on a hyperthyroid patient is dangerous, prior to thyroidectomy, preoperative treatment with antithyroid drugs is given to render the patient euthyroid. Each of these treatments has advantages and disadvantages, and no single treatment approach is considered the best for everyone.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup>
</p><p>Treatment with antithyroid medications must be administered for six months to two years to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. The risk of recurrence is about 40–50%, and lifelong treatment with antithyroid drugs carries some side effects such as <a href="/wiki/Agranulocytosis" title="Agranulocytosis">agranulocytosis</a> and <a href="/wiki/Liver_disease" title="Liver disease">liver disease</a>.<sup id="cite_ref-:0_24-0" class="reference"><a href="#cite_note-:0-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells. Therapy with radioiodine is the most common treatment in the United States, while antithyroid drugs and/or thyroidectomy are used more often in Europe, Japan, and most of the rest of the world.
</p><p><a href="/wiki/Beta_blocker" title="Beta blocker">β-Blockers</a> (such as <a href="/wiki/Propranolol" title="Propranolol">propranolol</a>) may be used to inhibit the <a href="/wiki/Sympathetic_nervous_system" title="Sympathetic nervous system">sympathetic nervous system</a> symptoms of <a href="/wiki/Tachycardia" title="Tachycardia">tachycardia</a> and nausea until antithyroid treatments start to take effect. Pure β-blockers do not inhibit lid retraction in the eyes, which is mediated by alpha adrenergic receptors.
</p>
<div class="mw-heading mw-heading3"><h3 id="Antithyroid_drugs">Antithyroid drugs</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=10" title="Edit section: Antithyroid drugs"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>The main antithyroid drugs are <a href="/wiki/Carbimazole" title="Carbimazole">carbimazole</a> (in the UK), <a href="/wiki/Methimazole" class="mw-redirect" title="Methimazole">methimazole</a> (in the US), and <a href="/wiki/Propylthiouracil" title="Propylthiouracil">propylthiouracil</a>/PTU. These drugs block the binding of iodine and coupling of iodotyrosines. The most dangerous side effect is agranulocytosis (1/250, more in PTU). Others include <a href="/wiki/Neutropenia" title="Neutropenia">granulocytopenia</a> (dose-dependent, which improves on cessation of the drug) and <a href="/wiki/Aplastic_anemia" title="Aplastic anemia">aplastic anemia</a>. Patients on these medications should see a doctor if they develop sore throat or fever. The most common side effects are rash and <a href="/wiki/Peripheral_neuropathy" title="Peripheral neuropathy">peripheral neuritis</a>. These drugs also cross the <a href="/wiki/Placenta" title="Placenta">placenta</a> and are secreted in breast milk. <a href="/wiki/Lugol%27s_iodine" title="Lugol's iodine">Lugol's iodine</a> may be used to block hormone synthesis before surgery.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (June 2022)">citation needed</span></a></i>]</sup>
</p><p>A <a href="/wiki/Randomized_control_trial" class="mw-redirect" title="Randomized control trial">randomized control trial</a> testing single-dose treatment for Graves found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).<sup id="cite_ref-pmid11298092_25-0" class="reference"><a href="#cite_note-pmid11298092-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup>
</p><p>No difference in outcome was shown for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are a positive <a href="/wiki/Thyrotropin_receptor" title="Thyrotropin receptor">TSHr</a> <a href="/wiki/Antibody" title="Antibody">antibody</a> (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (<a href="/wiki/Sensitivity_and_specificity" title="Sensitivity and specificity">sensitivity</a> 39%, <a href="/wiki/Sensitivity_and_specificity" title="Sensitivity and specificity">specificity</a> 98%), and a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.<sup id="cite_ref-pmid11331213_26-0" class="reference"><a href="#cite_note-pmid11331213-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Radioiodine">Radioiodine</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=11" title="Edit section: Radioiodine"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Basedow-vor-nach-RIT.jpg" class="mw-file-description"><img src="/media/wikipedia/commons/3/3f/Basedow-vor-nach-RIT.jpg" decoding="async" width="201" height="476" class="mw-file-element" data-file-width="201" data-file-height="476" /></a><figcaption>Scan of affected thyroid before (<i>top</i>) and after (<i>bottom</i>) <a href="/wiki/Radioiodine" class="mw-redirect" title="Radioiodine">radioiodine</a> therapy</figcaption></figure>
<p>Radioiodine (radioactive iodine-131) was developed in the early 1940s at the <a href="/wiki/Mallinckrodt_General_Clinical_Research_Center" class="mw-redirect" title="Mallinckrodt General Clinical Research Center">Mallinckrodt General Clinical Research Center</a>. This modality is suitable for most patients, although some prefer to use it mainly for older patients. Indications for radioiodine are failed medical therapy or surgery and where medical or surgical therapy are contraindicated. Hypothyroidism may be a complication of this therapy, but may be treated with thyroid hormones if it appears. The rationale for radioactive iodine is that it accumulates in the thyroid and irradiates the gland with its beta and gamma radiations, about 90% of the total radiation being emitted by the beta (electron) particles. The most common method of iodine-131 treatment is to administer a specified amount in microcuries per gram of thyroid gland based on palpation or radiodiagnostic imaging of the gland over 24 hours.<sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> Patients who receive the therapy must be monitored regularly with thyroid blood tests to ensure they are treated with thyroid hormone before they become symptomatically hypothyroid.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup>
</p><p>Contraindications to RAI are <a href="/wiki/Pregnancy" title="Pregnancy">pregnancy</a> (absolute), ophthalmopathy (relative; it can aggravate thyroid eye disease), or solitary <a href="/wiki/Thyroid_nodule" title="Thyroid nodule">nodules</a>.<sup id="cite_ref-btf-thyroid.org_29-0" class="reference"><a href="#cite_note-btf-thyroid.org-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup>
</p><p>Disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring eventual thyroid hormone supplementation in the form of a daily pill(s). The radioiodine treatment acts slowly (over months to years) to destroy the thyroid gland, and Graves' disease–associated hyperthyroidism is not cured in all persons by radioiodine, but has a relapse rate that depends on the dose of radioiodine which is administered.<sup id="cite_ref-btf-thyroid.org_29-1" class="reference"><a href="#cite_note-btf-thyroid.org-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> In rare cases, <a href="/wiki/Radiation-induced_thyroiditis" title="Radiation-induced thyroiditis">radiation induced thyroiditis</a> has been linked to this treatment.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Surgery">Surgery</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=12" title="Edit section: Surgery"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Further information: <a href="/wiki/Thyroidectomy" title="Thyroidectomy">Thyroidectomy</a></div>
<p>This modality is suitable for young people and pregnant females. Indications for thyroidectomy can be separated into absolute indications or relative indications. These indications aid in deciding which people would benefit most from surgery.<sup id="cite_ref-:0_24-1" class="reference"><a href="#cite_note-:0-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> The absolute indications are a large goiter (especially when compressing the <a href="/wiki/Vertebrate_trachea" class="mw-redirect" title="Vertebrate trachea">trachea</a>), suspicious nodules or suspected <a href="/wiki/Cancer" title="Cancer">cancer</a> (to pathologically examine the thyroid), and people with ophthalmopathy and additionally if it is the person's preferred method of treatment or if refusing to undergo radioactive iodine treatment. Pregnancy is advised to be delayed for six months after radioactive iodine treatment.<sup id="cite_ref-:0_24-2" class="reference"><a href="#cite_note-:0-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup>
</p><p>Both bilateral subtotal <a href="/wiki/Thyroidectomy" title="Thyroidectomy">thyroidectomy</a> and the Hartley-Dunhill procedure (hemithyroidectomy on one side and partial lobectomy on other side) are possible.
</p><p>Advantages are immediate cure and potential removal of <a href="/wiki/Carcinoma" title="Carcinoma">carcinoma</a>. Its risks are injury of the <a href="/wiki/Recurrent_laryngeal_nerve" title="Recurrent laryngeal nerve">recurrent laryngeal nerve</a>, <a href="/wiki/Hypoparathyroidism" title="Hypoparathyroidism">hypoparathyroidism</a> (due to removal of the <a href="/wiki/Parathyroid_gland" title="Parathyroid gland">parathyroid glands</a>), <a href="/wiki/Hematoma" title="Hematoma">hematoma</a> (which can be life-threatening if it compresses the trachea), relapse following medical treatment, infections (less common), and <a href="/wiki/Scarring" class="mw-redirect" title="Scarring">scarring</a>.<sup id="cite_ref-:0_24-3" class="reference"><a href="#cite_note-:0-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> The increase in the risk of nerve injury can be due to the increased vascularity of the thyroid parenchyma and the development of links between the thyroid capsule and the surrounding tissues. Reportedly, a 1% incidence exists of permanent <a href="/wiki/Vocal_fold_paresis" class="mw-redirect" title="Vocal fold paresis">recurrent laryngeal nerve paralysis</a> after complete thyroidectomy.<sup id="cite_ref-:0_24-4" class="reference"><a href="#cite_note-:0-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> Risks related to anesthesia are many, thus coordination with the anesthesiologist and patient optimization for surgery preoperatively are essential. Removal of the gland enables complete biopsy to be performed to have definite evidence of cancer anywhere in the thyroid. (Needle biopsies are not so accurate at predicting a benign state of the thyroid). No further treatment of the thyroid is required, unless cancer is detected. Radioiodine uptake study may be done after surgery, to ensure all remaining (potentially cancerous) thyroid cells (i.e., near the nerves to the vocal cords) are destroyed. Besides this, the only remaining treatment will be <a href="/wiki/Levothyroxine" title="Levothyroxine">levothyroxine</a>, or thyroid replacement pills to be taken for the rest of the patient's life.
</p><p>A 2013 review article concludes that surgery appears to be the most successful in the management of Graves' disease, with total thyroidectomy being the preferred surgical option.<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading3"><h3 id="Eyes">Eyes</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=13" title="Edit section: Eyes"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Mild cases are treated with lubricant eye drops or nonsteroidal anti-inflammatory drops. Severe cases threatening vision (corneal exposure or optic nerve compression) are treated with steroids or orbital decompression. In all cases, cessation of smoking is essential. Double vision can be corrected with prism glasses and surgery (the latter only when the process has been stable for a while).
</p><p>Difficulty closing eyes can be treated with lubricant gel at night, or with tape on the eyes to enable full, deep sleep.
</p><p>Orbital decompression can be performed to enable bulging eyes to retreat back into the head. Bone is removed from the skull behind the eyes, and space is made for the muscles and fatty tissue to fall back into the skull. <sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup>
</p><p>For management of clinically active Graves disease, orbitopathy (clinical activity score >2) with at least mild to moderate severity, intravenous glucocorticoids are the treatment of choice, usually administered in the form of pulse intravenous methylprednisolone. Studies have consistently shown that pulse intravenous methylprednisolone is superior to oral glucocorticoids both in terms of efficacy and decreased side effects for managing Graves' orbitopathy.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="Prognosis">Prognosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=14" title="Edit section: Prognosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>If left untreated, more serious <a href="/wiki/Complications_(medical)" class="mw-redirect" title="Complications (medical)">complications</a> could result, including <a href="/wiki/Birth_defect" title="Birth defect">birth defects</a> in pregnancy, increased risk of a <a href="/wiki/Miscarriage" title="Miscarriage">miscarriage</a>, bone mineral loss<sup id="cite_ref-Ken2001_34-0" class="reference"><a href="#cite_note-Ken2001-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> and, in extreme cases, death (e.g. indirectly through complications, or through a <a href="/wiki/Thyroid_storm" title="Thyroid storm">thyroid storm</a> event). Graves' disease is often accompanied by an increase in heart rate, which may lead to further heart complications, including loss of the normal heart rhythm (atrial fibrillation), which may lead to stroke. If the eyes are proptotic (bulging) enough that the lids do not close completely at night, dryness will occur – with the risk of a secondary corneal infection, which could lead to blindness. Pressure on the optic nerve behind the globe can lead to visual field defects and vision loss, as well. Prolonged untreated hyperthyroidism can lead to bone loss, which may resolve when treated.<sup id="cite_ref-Ken2001_34-1" class="reference"><a href="#cite_note-Ken2001-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="Epidemiology">Epidemiology</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=15" title="Edit section: Epidemiology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Causes_of_hyperthyroidism.png" class="mw-file-description"><img src="/media/wikipedia/commons/thumb/7/72/Causes_of_hyperthyroidism.png/220px-Causes_of_hyperthyroidism.png" decoding="async" width="220" height="209" class="mw-file-element" srcset="/media/wikipedia/commons/thumb/7/72/Causes_of_hyperthyroidism.png/330px-Causes_of_hyperthyroidism.png 1.5x, /media/wikipedia/commons/thumb/7/72/Causes_of_hyperthyroidism.png/440px-Causes_of_hyperthyroidism.png 2x" data-file-width="805" data-file-height="763" /></a><figcaption>Most common causes of <a href="/wiki/Hyperthyroidism" title="Hyperthyroidism">hyperthyroidism</a> by age<sup id="cite_ref-35" class="reference"><a href="#cite_note-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup></figcaption></figure>
<p>Graves' disease occurs in about 0.5% of people.<sup id="cite_ref-NEJM2008_4-6" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Graves' disease data has shown that the lifetime risk for women is around 3% and 0.5% for men.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> It occurs about 7.5 times more often in women than in men<sup id="cite_ref-NIH2012_1-24" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> and often starts between the ages of 40 and 60.<sup id="cite_ref-Nik2012_6-4" class="reference"><a href="#cite_note-Nik2012-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).<sup id="cite_ref-NIH2012_1-25" class="reference"><a href="#cite_note-NIH2012-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-NEJM2008_4-7" class="reference"><a href="#cite_note-NEJM2008-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="History">History</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=16" title="Edit section: History"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Graves disease owes its name to the <a href="/wiki/Anglo-Irish" class="mw-redirect" title="Anglo-Irish">Anglo-Irish</a> doctor <a href="/wiki/Robert_James_Graves" title="Robert James Graves">Robert James Graves</a>,<sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> who described a case of goiter with exophthalmos in 1835.<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> (<a href="/wiki/Medical_eponyms" class="mw-redirect" title="Medical eponyms">Medical eponyms</a> are often styled nonpossessively; thus <i>Graves' disease</i> and <i>Graves disease</i> are variant stylings of the same term.)
</p><p>The German <a href="/wiki/Karl_Adolph_von_Basedow" title="Karl Adolph von Basedow">Karl Adolph von Basedow</a> independently reported the same constellation of symptoms in 1840.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> As a result, on the European continent, the terms "Basedow syndrome",<sup id="cite_ref-WNI_41-0" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> "Basedow disease", or "Morbus Basedow"<sup id="cite_ref-TMHP_42-0" class="reference"><a href="#cite_note-TMHP-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> are more common than "Graves' disease".<sup id="cite_ref-WNI_41-1" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup>
</p><p>Graves disease<sup id="cite_ref-WNI_41-2" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-TMHP_42-1" class="reference"><a href="#cite_note-TMHP-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> has also been called <i>exophthalmic goiter</i>.<sup id="cite_ref-TMHP_42-2" class="reference"><a href="#cite_note-TMHP-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup>
</p><p>Less commonly, it has been known as Parry disease,<sup id="cite_ref-WNI_41-3" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-TMHP_42-3" class="reference"><a href="#cite_note-TMHP-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> Begbie disease, Flajan disease, Flajani–Basedow syndrome, and Marsh disease.<sup id="cite_ref-WNI_41-4" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> These names for the disease were derived from <a href="/wiki/Caleb_Hillier_Parry" title="Caleb Hillier Parry">Caleb Hillier Parry</a>, <a href="/wiki/James_Begbie" title="James Begbie">James Begbie</a>, <a href="/w/index.php?title=Giuseppe_Flajani&action=edit&redlink=1" class="new" title="Giuseppe Flajani (page does not exist)">Giuseppe Flajani</a>, and <a href="/wiki/Sir_Henry_Marsh" class="mw-redirect" title="Sir Henry Marsh"> Henry Marsh</a>.<sup id="cite_ref-WNI_41-5" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> Early reports, not widely circulated, of cases of goiter with exophthalmos were published by the Italians Giuseppe Flajani<sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> and Antonio Giuseppe Testa,<sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> in 1802 and 1810, respectively.<sup id="cite_ref-46" class="reference"><a href="#cite_note-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> Prior to these, Caleb Hillier Parry,<sup id="cite_ref-47" class="reference"><a href="#cite_note-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> a notable provincial physician in England of the late 18th century (and a friend of <a href="/w/index.php?title=Edward_Miller-Gallus&action=edit&redlink=1" class="new" title="Edward Miller-Gallus (page does not exist)">Edward Miller-Gallus</a>),<sup id="cite_ref-48" class="reference"><a href="#cite_note-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> described a case in 1786. This case was not published until 1825 - ten years ahead of Graves.<sup id="cite_ref-49" class="reference"><a href="#cite_note-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup>
</p><p>However, fair credit for the first description of Graves disease goes to the 12th-century <a href="/wiki/Islamic_medicine" class="mw-redirect" title="Islamic medicine">Persian physician</a> <a href="/wiki/Zayn_al-Din_al-Jurjani" class="mw-redirect" title="Zayn al-Din al-Jurjani">Sayyid Ismail al-Jurjani</a>,<sup id="cite_ref-50" class="reference"><a href="#cite_note-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> who noted the association of goiter and exophthalmos in his <a href="/wiki/Zayn_al-Din_al-Jurjani#Thesaurus_of_the_Shah_of_Khwarazm" class="mw-redirect" title="Zayn al-Din al-Jurjani"><i>Thesaurus of the Shah of Khwarazm</i></a>, the major medical dictionary of its time.<sup id="cite_ref-WNI_41-6" class="reference"><a href="#cite_note-WNI-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-51" class="reference"><a href="#cite_note-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="Society_and_culture">Society and culture</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=17" title="Edit section: Society and culture"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<div class="mw-heading mw-heading3"><h3 id="Notable_cases">Notable cases</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=18" title="Edit section: Notable cases"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Marty_Feldman.png" class="mw-file-description"><img src="/media/wikipedia/commons/1/15/Marty_Feldman.png" decoding="async" width="271" height="462" class="mw-file-element" data-file-width="271" data-file-height="462" /></a><figcaption><a href="/wiki/Marty_Feldman" title="Marty Feldman">Marty Feldman</a> used his bulging eyes, caused by Graves' disease, for comedic effect.</figcaption></figure>
<ul><li><a href="/wiki/Ayaka" title="Ayaka">Ayaka</a>, Japanese singer, was diagnosed with Graves disease in 2007. After going public with her diagnosis in 2009, she took a two-year hiatus from music to focus on treatment.<sup id="cite_ref-52" class="reference"><a href="#cite_note-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-53" class="reference"><a href="#cite_note-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Susan_Blow" title="Susan Blow">Susan Elizabeth Blow</a>, American educator and founder of the first publicly funded kindergarten in the United States, was forced to retire and seek treatment for Graves disease in 1884.<sup id="cite_ref-54" class="reference"><a href="#cite_note-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/George_H._W._Bush" title="George H. W. Bush">George H. W. Bush</a>, former U.S. president, developed new <a href="/wiki/Atrial_fibrillation" title="Atrial fibrillation">atrial fibrillation</a> and was diagnosed in 1991 with <a href="/wiki/Hyperthyroidism" title="Hyperthyroidism">hyperthyroidism</a> due to the disease and treated with radioactive iodine.<sup id="cite_ref-55" class="reference"><a href="#cite_note-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> The president's wife, <a href="/wiki/Barbara_Bush" title="Barbara Bush">Barbara Bush</a>, also developed the disease around the same time, which, in her case, produced severe infiltrative <a href="/wiki/Exophthalmos" title="Exophthalmos">exophthalmos</a>.<sup id="cite_ref-56" class="reference"><a href="#cite_note-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Rodney_Dangerfield" title="Rodney Dangerfield">Rodney Dangerfield</a>, American comedian and actor<sup id="cite_ref-57" class="reference"><a href="#cite_note-57"><span class="cite-bracket">[</span>57<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Gail_Devers" title="Gail Devers">Gail Devers</a>, American sprinter: A doctor considered amputating her feet after she developed blistering and swelling following radiation treatment for Graves' disease, but she went on to recover and win Olympic medals.</li>
<li><a href="/wiki/Missy_Elliott" title="Missy Elliott">Missy Elliott</a>, American hip-hop artist<sup id="cite_ref-58" class="reference"><a href="#cite_note-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Marty_Feldman" title="Marty Feldman">Marty Feldman</a>, British comedy writer, comedian and actor<sup id="cite_ref-59" class="reference"><a href="#cite_note-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-60" class="reference"><a href="#cite_note-60"><span class="cite-bracket">[</span>60<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Sia" title="Sia">Sia</a>, Australian singer and songwriter<sup id="cite_ref-61" class="reference"><a href="#cite_note-61"><span class="cite-bracket">[</span>61<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Sammy_Gravano" title="Sammy Gravano">Sammy Gravano</a>, Italian-American former underboss of the Gambino crime family<sup id="cite_ref-62" class="reference"><a href="#cite_note-62"><span class="cite-bracket">[</span>62<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Jim_Hamilton_(rugby_union)" title="Jim Hamilton (rugby union)">Jim Hamilton</a>, Scottish rugby player, discovered he had Graves' disease shortly after retiring from the sport in 2017.<sup id="cite_ref-63" class="reference"><a href="#cite_note-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Heino" title="Heino">Heino</a>, German folk singer, whose dark sunglasses (worn to hide his symptoms) became part of his trademark look<sup id="cite_ref-64" class="reference"><a href="#cite_note-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Herbert_Howells" title="Herbert Howells">Herbert Howells</a>, British composer; the first person to be treated with radium injections<sup id="cite_ref-65" class="reference"><a href="#cite_note-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Yayoi_Kusama" title="Yayoi Kusama">Yayoi Kusama</a>, Japanese artist<sup id="cite_ref-66" class="reference"><a href="#cite_note-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Nadezhda_Krupskaya" title="Nadezhda Krupskaya">Nadezhda Krupskaya</a>, Russian Communist and wife of <a href="/wiki/Vladimir_Lenin" title="Vladimir Lenin">Vladimir Lenin</a><sup id="cite_ref-67" class="reference"><a href="#cite_note-67"><span class="cite-bracket">[</span>67<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Umm_Kulthum" title="Umm Kulthum">Umm Kulthum</a> was an Egyptian singer, songwriter, and film actress active from the 1920s to the 1970s.</li>
<li><a href="/wiki/Barbara_Leigh" title="Barbara Leigh">Barbara Leigh</a>, an American former actress and fashion model, now spokeswoman for the National Graves' Disease Foundation<sup id="cite_ref-68" class="reference"><a href="#cite_note-68"><span class="cite-bracket">[</span>68<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Keiko_Masuda" title="Keiko Masuda">Keiko Masuda</a>, Japanese singer and one-half of the duo <a href="/wiki/Pink_Lady_(duo)" title="Pink Lady (duo)">Pink Lady</a>.<sup id="cite_ref-69" class="reference"><a href="#cite_note-69"><span class="cite-bracket">[</span>69<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-70" class="reference"><a href="#cite_note-70"><span class="cite-bracket">[</span>70<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-71" class="reference"><a href="#cite_note-71"><span class="cite-bracket">[</span>71<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-72" class="reference"><a href="#cite_note-72"><span class="cite-bracket">[</span>72<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Y%C5%ABko_Miyamura" title="Yūko Miyamura">Yūko Miyamura</a>, Japanese voice actress<sup id="cite_ref-73" class="reference"><a href="#cite_note-73"><span class="cite-bracket">[</span>73<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Christopher_Monckton,_3rd_Viscount_Monckton_of_Brenchley" title="Christopher Monckton, 3rd Viscount Monckton of Brenchley">Lord Monckton</a>, former <a href="/wiki/UK_Independence_Party" title="UK Independence Party">UKIP</a> and <a href="/wiki/Conservative_Party_(UK)" title="Conservative Party (UK)">Conservative</a> politician; notorious promoter of <a href="/wiki/Climate_change_denial" title="Climate change denial">climate change denial</a><sup id="cite_ref-74" class="reference"><a href="#cite_note-74"><span class="cite-bracket">[</span>74<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-75" class="reference"><a href="#cite_note-75"><span class="cite-bracket">[</span>75<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Sophia_Parnok" title="Sophia Parnok">Sophia Parnok</a>, Russian poet<sup id="cite_ref-76" class="reference"><a href="#cite_note-76"><span class="cite-bracket">[</span>76<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-77" class="reference"><a href="#cite_note-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-78" class="reference"><a href="#cite_note-78"><span class="cite-bracket">[</span>78<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Cecil_Spring_Rice" title="Cecil Spring Rice">Sir Cecil Spring Rice</a>, British ambassador to the United States during World War I, died suddenly of the disease in 1918.<sup id="cite_ref-79" class="reference"><a href="#cite_note-79"><span class="cite-bracket">[</span>79<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Daisy_Ridley" title="Daisy Ridley">Daisy Ridley</a>, British actress<sup id="cite_ref-80" class="reference"><a href="#cite_note-80"><span class="cite-bracket">[</span>80<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Christina_Rossetti" title="Christina Rossetti">Christina Rossetti</a>, English Victorian-era poet<sup id="cite_ref-81" class="reference"><a href="#cite_note-81"><span class="cite-bracket">[</span>81<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Maggie_Smith" title="Maggie Smith">Dame Maggie Smith</a>, British actress<sup id="cite_ref-82" class="reference"><a href="#cite_note-82"><span class="cite-bracket">[</span>82<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Mary_Webb" title="Mary Webb">Mary Webb</a>, British novelist and poet<sup id="cite_ref-83" class="reference"><a href="#cite_note-83"><span class="cite-bracket">[</span>83<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Wendy_Williams" title="Wendy Williams">Wendy Williams</a>, American TV show host<sup id="cite_ref-84" class="reference"><a href="#cite_note-84"><span class="cite-bracket">[</span>84<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Act_Yasukawa" title="Act Yasukawa">Act Yasukawa</a>, Japanese professional wrestler<sup id="cite_ref-85" class="reference"><a href="#cite_note-85"><span class="cite-bracket">[</span>85<span class="cite-bracket">]</span></a></sup></li></ul>
<div class="mw-heading mw-heading3"><h3 id="Literature">Literature</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=19" title="Edit section: Literature"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<ul><li>In <a href="/wiki/Italo_Svevo" title="Italo Svevo">Italo Svevo</a>'s novel <i><a href="/wiki/Zeno%27s_Conscience" title="Zeno's Conscience">Zeno's Conscience</a></i>, character Ada develops the disease.<sup id="cite_ref-86" class="reference"><a href="#cite_note-86"><span class="cite-bracket">[</span>86<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-87" class="reference"><a href="#cite_note-87"><span class="cite-bracket">[</span>87<span class="cite-bracket">]</span></a></sup></li>
<li><a href="/wiki/Ern_Malley" class="mw-redirect" title="Ern Malley">Ern Malley</a> was an acclaimed Australian poet whose work was not published until after his death from Graves' disease in 1943. However, Malley's existence and entire biography was actually later revealed to be a <a href="/wiki/Literary_hoax" class="mw-redirect" title="Literary hoax">literary hoax</a>.</li></ul>
<div class="mw-heading mw-heading2"><h2 id="Research">Research</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=20" title="Edit section: Research"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<p>Agents that act as antagonists at thyroid stimulating hormone receptors are under investigation as a possible treatment for Graves' disease.<sup id="cite_ref-88" class="reference"><a href="#cite_note-88"><span class="cite-bracket">[</span>88<span class="cite-bracket">]</span></a></sup>
</p>
<div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=21" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist">
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<li id="cite_note-AR-2"><span class="mw-cite-backlink"><b><a href="#cite_ref-AR_2-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.autoimmuneregistry.org/graves-disease">"Graves' disease"</a>. <i>Autoimmune Registry Inc</i><span class="reference-accessdate">. Retrieved <span class="nowrap">15 June</span> 2022</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=Autoimmune+Registry+Inc.&rft.atitle=Graves%27+disease&rft_id=https%3A%2F%2Fwww.autoimmuneregistry.org%2Fgraves-disease&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-Men2014-3"><span class="mw-cite-backlink">^ <a href="#cite_ref-Men2014_3-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Men2014_3-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Men2014_3-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMenconiMarcocciMarinò2014" class="citation journal cs1">Menconi F, Marcocci C, Marinò M (2014). "Diagnosis and classification of Graves disease". <i>Autoimmunity Reviews</i>. <b>13</b> (4–5): 398–402. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.autrev.2014.01.013">10.1016/j.autrev.2014.01.013</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/24424182">24424182</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Autoimmunity+Reviews&rft.atitle=Diagnosis+and+classification+of+Graves+disease&rft.volume=13&rft.issue=4%E2%80%935&rft.pages=398-402&rft.date=2014&rft_id=info%3Adoi%2F10.1016%2Fj.autrev.2014.01.013&rft_id=info%3Apmid%2F24424182&rft.aulast=Menconi&rft.aufirst=F&rft.au=Marcocci%2C+C&rft.au=Marin%C3%B2%2C+M&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-NEJM2008-4"><span class="mw-cite-backlink">^ <a href="#cite_ref-NEJM2008_4-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-5"><sup><i><b>f</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-6"><sup><i><b>g</b></i></sup></a> <a href="#cite_ref-NEJM2008_4-7"><sup><i><b>h</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBrent2008" class="citation journal cs1">Brent GA (June 2008). "Clinical practice. Grave disease". <i>The New England Journal of Medicine</i>. <b>358</b> (24): 2594–605. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1056%2FNEJMcp0801880">10.1056/NEJMcp0801880</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18550875">18550875</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Clinical+practice.+Grave+disease&rft.volume=358&rft.issue=24&rft.pages=2594-605&rft.date=2008-06&rft_id=info%3Adoi%2F10.1056%2FNEJMcp0801880&rft_id=info%3Apmid%2F18550875&rft.aulast=Brent&rft.aufirst=GA&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-Hen2015-5"><span class="mw-cite-backlink">^ <a href="#cite_ref-Hen2015_5-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Hen2015_5-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Hen2015_5-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBurchCooper2015" class="citation journal cs1">Burch HB, Cooper DS (December 2015). "Management of Graves Disease: A Review". <i>JAMA</i>. <b>314</b> (23): 2544–54. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1001%2Fjama.2015.16535">10.1001/jama.2015.16535</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/26670972">26670972</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Management+of+Graves+Disease%3A+A+Review&rft.volume=314&rft.issue=23&rft.pages=2544-54&rft.date=2015-12&rft_id=info%3Adoi%2F10.1001%2Fjama.2015.16535&rft_id=info%3Apmid%2F26670972&rft.aulast=Burch&rft.aufirst=HB&rft.au=Cooper%2C+DS&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-Nik2012-6"><span class="mw-cite-backlink">^ <a href="#cite_ref-Nik2012_6-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Nik2012_6-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Nik2012_6-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-Nik2012_6-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-Nik2012_6-4"><sup><i><b>e</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNikiforovBiddingerNikiforovaBiddinger2012" class="citation book cs1">Nikiforov YE, Biddinger PW, Nikiforova LD, Biddinger PW (2012). <a rel="nofollow" class="external text" href="https://books.google.com/books?id=jX1h00B4QJoC&pg=PA69"><i>Diagnostic pathology and molecular genetics of the thyroid</i></a> (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 69. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/9781451114553" title="Special:BookSources/9781451114553"><bdi>9781451114553</bdi></a>. <a rel="nofollow" class="external text" href="https://web.archive.org/web/20170908171950/https://books.google.com/books?id=jX1h00B4QJoC&pg=PA69">Archived</a> from the original on 2017-09-08.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Diagnostic+pathology+and+molecular+genetics+of+the+thyroid&rft.place=Philadelphia&rft.pages=69&rft.edition=2nd&rft.pub=Wolters+Kluwer+Health%2FLippincott+Williams+%26+Wilkins&rft.date=2012&rft.isbn=9781451114553&rft.aulast=Nikiforov&rft.aufirst=Yuri+E.&rft.au=Biddinger%2C+Paul+W.&rft.au=Nikiforova%2C+Lester+D.R.&rft.au=Biddinger%2C+Paul+W.&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3DjX1h00B4QJoC%26pg%3DPA69&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-13"><span class="mw-cite-backlink"><b><a href="#cite_ref-13">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHansenWenzelBrixHegedüs2006" class="citation journal cs1">Hansen PS, Wenzel BE, Brix TH, Hegedüs L (October 2006). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809723">"Yersinia enterocolitica infection does not confer an increased risk of thyroid antibodies: evidence from a Danish twin study"</a>. <i>Clinical and Experimental Immunology</i>. <b>146</b> (1): 32–8. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1365-2249.2006.03183.x">10.1111/j.1365-2249.2006.03183.x</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809723">1809723</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16968395">16968395</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Clinical+and+Experimental+Immunology&rft.atitle=Yersinia+enterocolitica+infection+does+not+confer+an+increased+risk+of+thyroid+antibodies%3A+evidence+from+a+Danish+twin+study&rft.volume=146&rft.issue=1&rft.pages=32-8&rft.date=2006-10&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1809723%23id-name%3DPMC&rft_id=info%3Apmid%2F16968395&rft_id=info%3Adoi%2F10.1111%2Fj.1365-2249.2006.03183.x&rft.aulast=Hansen&rft.aufirst=PS&rft.au=Wenzel%2C+BE&rft.au=Brix%2C+TH&rft.au=Heged%C3%BCs%2C+L&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1809723&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-30"><span class="mw-cite-backlink"><b><a href="#cite_ref-30">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMizokamiHamadaMarutaHigashi2016" class="citation journal cs1">Mizokami, Tetsuya; Hamada, Katsuhiko; Maruta, Tetsushi; Higashi, Kiichiro; Tajiri, Junichi (September 2016). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091234">"Painful Radiation Thyroiditis after 131I Therapy for Graves' Hyperthyroidism: Clinical Features and Ultrasonographic Findings in Five Cases"</a>. <i>European Thyroid Journal</i>. <b>5</b> (3): 201–206. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1159%2F000448398">10.1159/000448398</a>. <a href="/wiki/ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/issn/2235-0640">2235-0640</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091234">5091234</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/27843811">27843811</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=European+Thyroid+Journal&rft.atitle=Painful+Radiation+Thyroiditis+after+131I+Therapy+for+Graves%27+Hyperthyroidism%3A+Clinical+Features+and+Ultrasonographic+Findings+in+Five+Cases&rft.volume=5&rft.issue=3&rft.pages=201-206&rft.date=2016-09&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5091234%23id-name%3DPMC&rft.issn=2235-0640&rft_id=info%3Apmid%2F27843811&rft_id=info%3Adoi%2F10.1159%2F000448398&rft.aulast=Mizokami&rft.aufirst=Tetsuya&rft.au=Hamada%2C+Katsuhiko&rft.au=Maruta%2C+Tetsushi&rft.au=Higashi%2C+Kiichiro&rft.au=Tajiri%2C+Junichi&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5091234&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-31"><span class="mw-cite-backlink"><b><a href="#cite_ref-31">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGenoveseNoureldineGleesonTufano2013" class="citation journal cs1">Genovese BM, Noureldine SI, Gleeson EM, Tufano RP, Kandil E (February 2013). "What is the best definitive treatment for Graves' disease? A systematic review of the existing literature". <i>Annals of Surgical Oncology</i> (review). <b>20</b> (2): 660–7. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1245%2Fs10434-012-2606-x">10.1245/s10434-012-2606-x</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22956065">22956065</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:24759725">24759725</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Annals+of+Surgical+Oncology&rft.atitle=What+is+the+best+definitive+treatment+for+Graves%27+disease%3F+A+systematic+review+of+the+existing+literature&rft.volume=20&rft.issue=2&rft.pages=660-7&rft.date=2013-02&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A24759725%23id-name%3DS2CID&rft_id=info%3Apmid%2F22956065&rft_id=info%3Adoi%2F10.1245%2Fs10434-012-2606-x&rft.aulast=Genovese&rft.aufirst=BM&rft.au=Noureldine%2C+SI&rft.au=Gleeson%2C+EM&rft.au=Tufano%2C+RP&rft.au=Kandil%2C+E&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-32"><span class="mw-cite-backlink"><b><a href="#cite_ref-32">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFLimongiFeijóRodrigues_Lopes_E_SilvaAkaishi2020" class="citation journal cs1">Limongi, Roberto Murillo; Feijó, Eduardo Damous; Rodrigues Lopes E Silva, Marlos; Akaishi, Patrícia; Velasco E Cruz, Antônio Augusto; Christian Pieroni-Gonçalves, Allan; Pereira, Filipe; Devoto, Martin; Bernardini, Francesco; Marques, Victor; Tao, Jeremiah P. (February 2020). <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/31373985/">"Orbital Bone Decompression for Non-Thyroid Eye Disease Proptosis"</a>. <i>Ophthalmic Plastic and Reconstructive Surgery</i>. <b>36</b> (1): 13–16. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1097%2FIOP.0000000000001435">10.1097/IOP.0000000000001435</a>. <a href="/wiki/ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/issn/1537-2677">1537-2677</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/31373985">31373985</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:199388425">199388425</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Ophthalmic+Plastic+and+Reconstructive+Surgery&rft.atitle=Orbital+Bone+Decompression+for+Non-Thyroid+Eye+Disease+Proptosis&rft.volume=36&rft.issue=1&rft.pages=13-16&rft.date=2020-02&rft.issn=1537-2677&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A199388425%23id-name%3DS2CID&rft_id=info%3Apmid%2F31373985&rft_id=info%3Adoi%2F10.1097%2FIOP.0000000000001435&rft.aulast=Limongi&rft.aufirst=Roberto+Murillo&rft.au=Feij%C3%B3%2C+Eduardo+Damous&rft.au=Rodrigues+Lopes+E+Silva%2C+Marlos&rft.au=Akaishi%2C+Patr%C3%ADcia&rft.au=Velasco+E+Cruz%2C+Ant%C3%B4nio+Augusto&rft.au=Christian+Pieroni-Gon%C3%A7alves%2C+Allan&rft.au=Pereira%2C+Filipe&rft.au=Devoto%2C+Martin&rft.au=Bernardini%2C+Francesco&rft.au=Marques%2C+Victor&rft.au=Tao%2C+Jeremiah+P.&rft_id=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F31373985%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-33"><span class="mw-cite-backlink"><b><a href="#cite_ref-33">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRoyDuttaGhoshMukhopadhyay2015" class="citation journal cs1">Roy A, Dutta D, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, Chowdhury S (2015). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366772">"Efficacy and safety of low dose oral prednisolone as compared to pulse intravenous methylprednisolone in managing moderate severe Graves' orbitopathy: A randomized controlled trial"</a>. <i>Indian Journal of Endocrinology and Metabolism</i>. <b>19</b> (3): 351–8. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.4103%2F2230-8210.152770">10.4103/2230-8210.152770</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366772">4366772</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/25932389">25932389</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Indian+Journal+of+Endocrinology+and+Metabolism&rft.atitle=Efficacy+and+safety+of+low+dose+oral+prednisolone+as+compared+to+pulse+intravenous+methylprednisolone+in+managing+moderate+severe+Graves%27+orbitopathy%3A+A+randomized+controlled+trial&rft.volume=19&rft.issue=3&rft.pages=351-8&rft.date=2015&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4366772%23id-name%3DPMC&rft_id=info%3Apmid%2F25932389&rft_id=info%3Adoi%2F10.4103%2F2230-8210.152770&rft.aulast=Roy&rft.aufirst=A&rft.au=Dutta%2C+D&rft.au=Ghosh%2C+S&rft.au=Mukhopadhyay%2C+P&rft.au=Mukhopadhyay%2C+S&rft.au=Chowdhury%2C+S&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4366772&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-Ken2001-34"><span class="mw-cite-backlink">^ <a href="#cite_ref-Ken2001_34-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Ken2001_34-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBecker2001" class="citation book cs1">Becker, Kenneth L., ed. (2001). <a rel="nofollow" class="external text" href="https://books.google.com/books?id=FVfzRvaucq8C&pg=PA636"><i>Principles and practice of endocrinology and metabolism</i></a> (3 ed.). Philadelphia, Pa.: Lippincott, Williams & Wilkins. p. 636. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-7817-1750-2" title="Special:BookSources/978-0-7817-1750-2"><bdi>978-0-7817-1750-2</bdi></a>. <a rel="nofollow" class="external text" href="https://web.archive.org/web/20170908171950/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA636">Archived</a> from the original on 2017-09-08.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Principles+and+practice+of+endocrinology+and+metabolism&rft.place=Philadelphia%2C+Pa.&rft.pages=636&rft.edition=3&rft.pub=Lippincott%2C+Williams+%26+Wilkins&rft.date=2001&rft.isbn=978-0-7817-1750-2&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3DFVfzRvaucq8C%26pg%3DPA636&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-35"><span class="mw-cite-backlink"><b><a href="#cite_ref-35">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCarléPedersenKnudsenPerrild2011" class="citation journal cs1">Carlé, Allan; Pedersen, Inge Bülow; Knudsen, Nils; Perrild, Hans; Ovesen, Lars; Rasmussen, Lone Banke; Laurberg, Peter (2011). <a rel="nofollow" class="external text" href="https://doi.org/10.1530%2FEJE-10-1155">"Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study"</a>. <i>European Journal of Endocrinology</i>. <b>164</b> (5): 801–809. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1530%2FEJE-10-1155">10.1530/EJE-10-1155</a></span>. <a href="/wiki/ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/issn/0804-4643">0804-4643</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21357288">21357288</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=European+Journal+of+Endocrinology&rft.atitle=Epidemiology+of+subtypes+of+hyperthyroidism+in+Denmark%3A+a+population-based+study&rft.volume=164&rft.issue=5&rft.pages=801-809&rft.date=2011&rft.issn=0804-4643&rft_id=info%3Apmid%2F21357288&rft_id=info%3Adoi%2F10.1530%2FEJE-10-1155&rft.aulast=Carl%C3%A9&rft.aufirst=Allan&rft.au=Pedersen%2C+Inge+B%C3%BClow&rft.au=Knudsen%2C+Nils&rft.au=Perrild%2C+Hans&rft.au=Ovesen%2C+Lars&rft.au=Rasmussen%2C+Lone+Banke&rft.au=Laurberg%2C+Peter&rft_id=https%3A%2F%2Fdoi.org%2F10.1530%252FEJE-10-1155&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-36"><span class="mw-cite-backlink"><b><a href="#cite_ref-36">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPokhrelBhusal2020" class="citation cs2">Pokhrel, Binod; Bhusal, Kamal (2020), <a rel="nofollow" class="external text" href="http://www.ncbi.nlm.nih.gov/books/NBK448195/">"Graves Disease"</a>, <i>StatPearls</i>, Treasure Island (FL): StatPearls Publishing, <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/28846288">28846288</a><span class="reference-accessdate">, retrieved <span class="nowrap">2020-12-04</span></span></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=StatPearls&rft.atitle=Graves+Disease&rft.date=2020&rft_id=info%3Apmid%2F28846288&rft.aulast=Pokhrel&rft.aufirst=Binod&rft.au=Bhusal%2C+Kamal&rft_id=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fbooks%2FNBK448195%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-37"><span class="mw-cite-backlink"><b><a href="#cite_ref-37">^</a></b></span> <span class="reference-text"><i><a rel="nofollow" class="external text" href="http://www.whonamedit.com/doctor.cfm/695.html">Mathew Graves</a></i> at <a href="/wiki/Who_Named_It%3F" class="mw-redirect" title="Who Named It?">Who Named It?</a></span>
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<li id="cite_note-38"><span class="mw-cite-backlink"><b><a href="#cite_ref-38">^</a></b></span> <span class="reference-text">Graves, RJ. <a rel="nofollow" class="external text" href="https://archive.org/details/p2londonmedicals07londuoft"><i>Newly observed affection of the thyroid gland in females</i></a> <a rel="nofollow" class="external text" href="https://web.archive.org/web/20160331121345/https://archive.org/details/p2londonmedicals07londuoft">Archived</a> 2016-03-31 at the <a href="/wiki/Wayback_Machine" title="Wayback Machine">Wayback Machine</a>. (Clinical lectures.) London Medical and Surgical Journal (Renshaw), 1835; 7 (part 2): 516–517. Reprinted in Medical Classics, 1940;5:33–36.</span>
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<li id="cite_note-39"><span class="mw-cite-backlink"><b><a href="#cite_ref-39">^</a></b></span> <span class="reference-text">Von Basedow, KA. <i>Exophthalmus durch Hypertrophie des Zellgewebes in der Augenhöhle</i>. <i>[Casper's] Wochenschrift für die gesammte Heilkunde</i>, Berlin, 1840, 6: 197–204; 220–228. Partial English translation in: Ralph Hermon Major (1884–1970): <i>Classic Descriptions of Disease</i>. Springfield, C. C. Thomas, 1932. 2nd edition, 1939; 3rd edition, 1945.</span>
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<li id="cite_note-40"><span class="mw-cite-backlink"><b><a href="#cite_ref-40">^</a></b></span> <span class="reference-text">Von Basedow, KA. "Die Glotzaugen". <i>[Casper's] Wochenschrift für die gesammte Heilkunde</i>, Berlin, 1848: 769–777.</span>
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<li id="cite_note-WNI-41"><span class="mw-cite-backlink">^ <a href="#cite_ref-WNI_41-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-WNI_41-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-WNI_41-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-WNI_41-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-WNI_41-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-WNI_41-5"><sup><i><b>f</b></i></sup></a> <a href="#cite_ref-WNI_41-6"><sup><i><b>g</b></i></sup></a></span> <span class="reference-text"><i><a rel="nofollow" class="external text" href="http://www.whonamedit.com/synd.cfm/1517.html">Basedow syndrome or disease</a></i> at <a href="/wiki/Who_Named_It%3F" class="mw-redirect" title="Who Named It?">Who Named It?</a> – the history and naming of the disease</span>
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<li id="cite_note-TMHP-42"><span class="mw-cite-backlink">^ <a href="#cite_ref-TMHP_42-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-TMHP_42-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-TMHP_42-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-TMHP_42-3"><sup><i><b>d</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRobinson,_Victor1939" class="citation encyclopaedia cs1">Robinson, Victor, ed. (1939). "Exophthalmic goiter, Basedow disease, Grave disesase". <i><a href="/wiki/The_Modern_Home_Physician,_A_New_Encyclopedia_of_Medical_Knowledge" class="mw-redirect" title="The Modern Home Physician, A New Encyclopedia of Medical Knowledge">The Modern Home Physician, A New Encyclopedia of Medical Knowledge</a></i>. WM. H. Wise & Company (New York).</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Exophthalmic+goiter%2C+Basedow+disease%2C+Grave+disesase&rft.btitle=The+Modern+Home+Physician%2C+A+New+Encyclopedia+of+Medical+Knowledge&rft.pub=WM.+H.+Wise+%26+Company+%28New+York%29&rft.date=1939&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span>, pages 82, 294, and 295.</span>
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<li id="cite_note-43"><span class="mw-cite-backlink"><b><a href="#cite_ref-43">^</a></b></span> <span class="reference-text"><i><a rel="nofollow" class="external text" href="http://www.emedicine.com/med/topic917.htm#">Goiter, Diffuse Toxic</a></i> at <a href="/wiki/EMedicine" title="EMedicine">eMedicine</a></span>
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<li id="cite_note-44"><span class="mw-cite-backlink"><b><a href="#cite_ref-44">^</a></b></span> <span class="reference-text">Flajani, G. <i>Sopra un tumor freddo nell'anterior parte del collo broncocele. (Osservazione LXVII)</i>. In Collezione d'osservazioni e reflessioni di chirurgia. Rome, Michele A Ripa Presso Lino Contedini, 1802;3:270–273.</span>
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<li id="cite_note-45"><span class="mw-cite-backlink"><b><a href="#cite_ref-45">^</a></b></span> <span class="reference-text">Testa, AG. <i>Delle malattie del cuore, loro cagioni, specie, segni e cura.</i> Bologna, 1810. 2nd edition in 3 volumes, Florence, 1823; Milano 1831; German translation, Halle, 1813.</span>
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<li id="cite_note-46"><span class="mw-cite-backlink"><b><a href="#cite_ref-46">^</a></b></span> <span class="reference-text"><i><a rel="nofollow" class="external text" href="http://www.whonamedit.com/doctor.cfm/1471.html">Giuseppe Flajani</a></i> at <a href="/wiki/Who_Named_It%3F" class="mw-redirect" title="Who Named It?">Who Named It?</a></span>
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<li id="cite_note-47"><span class="mw-cite-backlink"><b><a href="#cite_ref-47">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFParry1825" class="citation book cs1">Parry CH (1825). "Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart". <i>Collections from the unpublished medical writings of C. H. Parry</i>. London. pp. 111–129. <q>According to Garrison, Parry first noted the condition in 1786. He briefly reported it in his <i>Elements of Pathology and Therapeutics</i>, 1815. Reprinted in Medical Classics, 1940, 5: 8–30</q></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Enlargement+of+the+thyroid+gland+in+connection+with+enlargement+or+palpitations+of+the+heart&rft.btitle=Collections+from+the+unpublished+medical+writings+of+C.+H.+Parry&rft.place=London&rft.pages=111-129&rft.date=1825&rft.aulast=Parry&rft.aufirst=CH&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-48"><span class="mw-cite-backlink"><b><a href="#cite_ref-48">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHull1998" class="citation journal cs1">Hull G (June 1998). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296785">"Caleb Hillier Parry 1755-1822: a notable provincial physician"</a>. <i>Journal of the Royal Society of Medicine</i>. <b>91</b> (6): 335–8. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1177%2F014107689809100618">10.1177/014107689809100618</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296785">1296785</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/9771526">9771526</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+the+Royal+Society+of+Medicine&rft.atitle=Caleb+Hillier+Parry+1755-1822%3A+a+notable+provincial+physician&rft.volume=91&rft.issue=6&rft.pages=335-8&rft.date=1998-06&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1296785%23id-name%3DPMC&rft_id=info%3Apmid%2F9771526&rft_id=info%3Adoi%2F10.1177%2F014107689809100618&rft.aulast=Hull&rft.aufirst=G&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1296785&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-50"><span class="mw-cite-backlink"><b><a href="#cite_ref-50">^</a></b></span> <span class="reference-text">Sayyid Ismail Al-Jurjani. <i>Thesaurus of the Shah of Khwarazm</i>.</span>
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<li id="cite_note-51"><span class="mw-cite-backlink"><b><a href="#cite_ref-51">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFLjunggren1983" class="citation journal cs1">Ljunggren JG (August 1983). "[Who was the man behind the syndrome: Ismail al-Jurjani, Testa, Flagani, Parry, Graves or Basedow? Use the term hyperthyreosis instead]". <i>Läkartidningen</i>. <b>80</b> (32–33): 2902. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/6355710">6355710</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=L%C3%A4kartidningen&rft.atitle=%5BWho+was+the+man+behind+the+syndrome%3A+Ismail+al-Jurjani%2C+Testa%2C+Flagani%2C+Parry%2C+Graves+or+Basedow%3F+Use+the+term+hyperthyreosis+instead%5D&rft.volume=80&rft.issue=32%E2%80%9333&rft.pages=2902&rft.date=1983-08&rft_id=info%3Apmid%2F6355710&rft.aulast=Ljunggren&rft.aufirst=JG&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-52"><span class="mw-cite-backlink"><b><a href="#cite_ref-52">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1 cs1-prop-foreign-lang-source"><a rel="nofollow" class="external text" href="http://beauty.oricon.co.jp/trend-culture/trend/news/64835/full/">"水嶋ヒロ・絢香、2ショット会見で結婚報告 絢香はバセドウ病を告白、年内で休業へ"</a> (in Japanese). <a href="/wiki/Oricon" title="Oricon">Oricon</a>. April 3, 2009. <a rel="nofollow" class="external text" href="https://web.archive.org/web/20151208132540/http://beauty.oricon.co.jp/trend-culture/trend/news/64835/full/">Archived</a> from the original on December 8, 2015<span class="reference-accessdate">. Retrieved <span class="nowrap">November 19,</span> 2015</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=%E6%B0%B4%E5%B6%8B%E3%83%92%E3%83%AD%E3%83%BB%E7%B5%A2%E9%A6%99%E3%80%812%E3%82%B7%E3%83%A7%E3%83%83%E3%83%88%E4%BC%9A%E8%A6%8B%E3%81%A7%E7%B5%90%E5%A9%9A%E5%A0%B1%E5%91%8A+%E7%B5%A2%E9%A6%99%E3%81%AF%E3%83%90%E3%82%BB%E3%83%89%E3%82%A6%E7%97%85%E3%82%92%E5%91%8A%E7%99%BD%E3%80%81%E5%B9%B4%E5%86%85%E3%81%A7%E4%BC%91%E6%A5%AD%E3%81%B8&rft.pub=Oricon&rft.date=2009-04-03&rft_id=http%3A%2F%2Fbeauty.oricon.co.jp%2Ftrend-culture%2Ftrend%2Fnews%2F64835%2Ffull%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-80"><span class="mw-cite-backlink"><b><a href="#cite_ref-80">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.hollywoodreporter.com/lifestyle/lifestyle-news/daisy-ridley-graves-disease-1235966996/">"Daisy Ridley Reveals Graves' Disease Diagnosis"</a>. <i><a href="/wiki/The_Hollywood_Reporter" title="The Hollywood Reporter">The Hollywood Reporter</a></i>. 6 August 2024.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=The+Hollywood+Reporter&rft.atitle=Daisy+Ridley+Reveals+Graves%27+Disease+Diagnosis&rft.date=2024-08-06&rft_id=https%3A%2F%2Fwww.hollywoodreporter.com%2Flifestyle%2Flifestyle-news%2Fdaisy-ridley-graves-disease-1235966996%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-83"><span class="mw-cite-backlink"><b><a href="#cite_ref-83">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="http://www.marywebbsociety.co.uk/biography/">"Biography"</a>. <a rel="nofollow" class="external text" href="https://web.archive.org/web/20150716204649/http://www.marywebbsociety.co.uk/biography/">Archived</a> from the original on 2015-07-16<span class="reference-accessdate">. Retrieved <span class="nowrap">2015-07-16</span></span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=unknown&rft.btitle=Biography&rft_id=http%3A%2F%2Fwww.marywebbsociety.co.uk%2Fbiography%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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<li id="cite_note-84"><span class="mw-cite-backlink"><b><a href="#cite_ref-84">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMelas2018" class="citation web cs1">Melas C (February 21, 2018). <a rel="nofollow" class="external text" href="https://us.cnn.com/2018/02/21/entertainment/wendy-williams-graves-disease/index.html">"Wendy Williams announces show hiatus due to Graves' disease"</a>. <i>CNN</i><span class="reference-accessdate">. Retrieved <span class="nowrap">February 21,</span> 2018</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=CNN&rft.atitle=Wendy+Williams+announces+show+hiatus+due+to+Graves%27+disease&rft.date=2018-02-21&rft.aulast=Melas&rft.aufirst=Chloe&rft_id=https%3A%2F%2Fus.cnn.com%2F2018%2F02%2F21%2Fentertainment%2Fwendy-williams-graves-disease%2Findex.html&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></span>
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</li>
</ol></div></div>
<div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Graves%27_disease&action=edit&section=22" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div>
<ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://ghr.nlm.nih.gov/condition/graves-disease">"Graves' disease"</a>. <i>Genetics Home Reference</i>. U.S. National Library of Medicine.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=Genetics+Home+Reference&rft.atitle=Graves%27+disease&rft_id=https%3A%2F%2Fghr.nlm.nih.gov%2Fcondition%2Fgraves-disease&rfr_id=info%3Asid%2Fen.wikipedia.org%3AGraves%27+disease" class="Z3988"></span></li>
<li><a rel="nofollow" class="external free" href="https://www.ncbi.nlm.nih.gov/gene/?term=graves">https://www.ncbi.nlm.nih.gov/gene/?term=graves</a> about graves on ncbi</li></ul>
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margin:0.5em 0 0.5em 0;;padding:3px"><table class="nowraplinks navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;background: #EAECF0;color:black;">Classification</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><div style="position:relative; float:right; font-size:0.8em;"><a href="/wiki/Q16483" class="extiw" title="d:Q16483">D</a></div><div class="hlist" style="text-align:left;"><ul><li><b><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/ICD-11" title="ICD-11">11</a></b>: <a rel="nofollow" class="external text" href="https://icd.who.int/browse/latest-release/mms/en#713028385">5A02.0</a></li><li><b><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/ICD-10" title="ICD-10">10</a></b>: <a rel="nofollow" class="external text" href="https://icd.who.int/browse10/2019/en#/E05.0">E05.0</a></li><li><b><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/ICD-10-CM" title="ICD-10-CM">10-CM</a></b>: <a rel="nofollow" class="external text" href="https://icd10cmtool.cdc.gov/?fy=FY2024&query=E05.0">E05.0</a></li><li><b><a href="/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems" class="mw-redirect" title="International Statistical Classification of Diseases and Related Health Problems">ICD</a>-<a href="/wiki/List_of_ICD-9_codes" title="List of ICD-9 codes">9-CM</a></b>: <a rel="nofollow" class="external text" href="http://www.icd9data.com/getICD9Code.ashx?icd9=242.0">242.0</a></li><li><b><a href="/wiki/Online_Mendelian_Inheritance_in_Man" title="Online Mendelian Inheritance in Man">OMIM</a></b>: <a rel="nofollow" class="external text" href="https://omim.org/entry/275000">275000</a></li><li><b><a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">MeSH</a></b>: <a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?ui=D006111">D006111</a></li><li><b><a href="/wiki/Diseases_Database" title="Diseases Database">DiseasesDB</a></b>: <a rel="nofollow" class="external text" href="http://www.diseasesdatabase.com/ddb5419.htm">5419</a></li><li><b><a href="/wiki/SNOMED_CT" title="SNOMED CT">SNOMED CT</a></b>: <a rel="nofollow" class="external text" href="http://snomed.info/id/353295004">353295004</a></li></ul></div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;background: #EAECF0;color:black;">External resources</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"><div class="hlist" style="text-align:left;"><ul><li><b><a href="/wiki/Curlie" class="mw-redirect" title="Curlie">Curlie</a></b>: <a rel="nofollow" class="external text" href="https://curlie.org/Health/Conditions_and_Diseases/Endocrine_Disorders/Thyroid/Hyperthyroidism/Graves%27_Disease/">Graves' disease</a></li><li><b><a href="/wiki/MedlinePlus" title="MedlinePlus">MedlinePlus</a></b>: <a rel="nofollow" class="external text" href="https://www.nlm.nih.gov/medlineplus/ency/article/000358.htm">000358</a></li><li><b><a href="/wiki/EMedicine" title="EMedicine">eMedicine</a></b>: <a rel="nofollow" class="external text" href="https://emedicine.medscape.com/med/929-overview">med/929</a> <a rel="nofollow" class="external text" href="https://www.emedicine.com/ped/topic899.htm#">ped/899</a></li></ul></div></div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Thyroid_disease" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Thyroid_disease" title="Template:Thyroid disease"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Thyroid_disease" title="Template talk:Thyroid disease"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Thyroid_disease" title="Special:EditPage/Template:Thyroid disease"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Thyroid_disease" style="font-size:114%;margin:0 4em"><a href="/wiki/Thyroid_disease" title="Thyroid disease">Thyroid disease</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Hypothyroidism" title="Hypothyroidism">Hypothyroidism</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Iodine_deficiency" title="Iodine deficiency">Iodine deficiency</a></li>
<li><a href="/wiki/Cretinism" class="mw-redirect" title="Cretinism">Cretinism</a>
<ul><li><a href="/wiki/Congenital_hypothyroidism" title="Congenital hypothyroidism">Congenital hypothyroidism</a></li></ul></li>
<li><a href="/wiki/Myxedema" title="Myxedema">Myxedema</a></li>
<li><a href="/wiki/Myxedema_coma" title="Myxedema coma">Myxedema coma</a></li>
<li><a href="/wiki/Euthyroid_sick_syndrome" title="Euthyroid sick syndrome">Euthyroid sick syndrome</a></li>
<li><a href="/wiki/Van_Wyk_and_Grumbach_syndrome" title="Van Wyk and Grumbach syndrome">Van Wyk-Grumbach syndrome</a></li>
<li>Signs and symptoms
<ul><li><a href="/wiki/Sign_of_Hertoghe" title="Sign of Hertoghe">Queen Anne's sign</a></li>
<li><a href="/wiki/Woltman_sign" title="Woltman sign">Woltman sign</a></li>
<li><a href="/wiki/Edema" title="Edema">Myoedema</a></li></ul></li>
<li><a href="/wiki/Thyroid_dyshormonogenesis" title="Thyroid dyshormonogenesis">Thyroid dyshormonogenesis</a></li>
<li><a href="/wiki/Pickardt_syndrome" title="Pickardt syndrome">Pickardt syndrome</a></li>
<li>Hypothyroid myopathy
<ul><li><a href="/wiki/Kocher%E2%80%93Debre%E2%80%93Semelaigne_syndrome" title="Kocher–Debre–Semelaigne syndrome">KDSS</a></li>
<li><a href="/wiki/Hoffmann_syndrome" title="Hoffmann syndrome">Hoffmann syndrome</a></li>
<li><a href="/wiki/Lambert%E2%80%93Eaton_myasthenic_syndrome" title="Lambert–Eaton myasthenic syndrome">LEMS</a></li>
<li>Atrophic type</li></ul></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Hyperthyroidism" title="Hyperthyroidism">Hyperthyroidism</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Hyperthyroxinemia" title="Hyperthyroxinemia">Hyperthyroxinemia</a>
<ul><li><a href="/wiki/Thyroid_hormone_resistance" title="Thyroid hormone resistance">Thyroid hormone resistance</a></li>
<li><a href="/wiki/Familial_dysalbuminemic_hyperthyroxinemia" title="Familial dysalbuminemic hyperthyroxinemia">Familial dysalbuminemic hyperthyroxinemia</a></li></ul></li>
<li><a href="/wiki/Hashitoxicosis" title="Hashitoxicosis">Hashitoxicosis</a></li>
<li><a href="/wiki/Thyrotoxicosis_factitia" title="Thyrotoxicosis factitia">Thyrotoxicosis factitia</a></li>
<li><a href="/wiki/Thyroid_storm" title="Thyroid storm">Thyroid storm</a></li>
<li><a href="/wiki/Amiodarone_induced_thyrotoxicosis" title="Amiodarone induced thyrotoxicosis">Amiodarone induced thyrotoxicosis</a></li>
<li>Hyperthyroid myopathy</li></ul>
</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a class="mw-selflink selflink">Graves' disease</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li>Signs and symptoms
<ul><li><a href="/wiki/Abadie%27s_sign_of_exophthalmic_goiter" title="Abadie's sign of exophthalmic goiter">Abadie's sign of exophthalmic goiter</a></li>
<li><a href="/wiki/Boston%27s_sign" title="Boston's sign">Boston's sign</a></li>
<li><a href="/wiki/Dalrymple%27s_sign" title="Dalrymple's sign">Dalrymple's sign</a></li>
<li><a href="/wiki/Stellwag%27s_sign" title="Stellwag's sign">Stellwag's sign</a></li>
<li><a href="/wiki/Von_Graefe%27s_sign" title="Von Graefe's sign">lid lag</a></li>
<li><a href="/wiki/Griffith%27s_sign" title="Griffith's sign">Griffith's sign</a></li>
<li><a href="/wiki/M%C3%B6bius_sign" title="Möbius sign">Möbius sign</a></li>
<li><a href="/wiki/Pretibial_myxedema" title="Pretibial myxedema">Pretibial myxedema</a></li></ul></li>
<li><a href="/wiki/Graves%27_ophthalmopathy" title="Graves' ophthalmopathy">Graves' ophthalmopathy</a></li></ul>
</div></td></tr></tbody></table><div>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Thyroiditis" title="Thyroiditis">Thyroiditis</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Acute_infectious_thyroiditis" title="Acute infectious thyroiditis">Acute infectious</a></li>
<li><a href="/wiki/Subacute_thyroiditis" title="Subacute thyroiditis">Subacute</a>
<ul><li><a href="/wiki/De_Quervain%27s_thyroiditis" title="De Quervain's thyroiditis">De Quervain's</a></li>
<li><a href="/wiki/Subacute_lymphocytic_thyroiditis" title="Subacute lymphocytic thyroiditis">Subacute lymphocytic</a></li>
<li><a href="/wiki/Palpation_thyroiditis" title="Palpation thyroiditis">Palpation</a></li></ul></li>
<li><a href="/wiki/Autoimmune_thyroiditis" class="mw-redirect" title="Autoimmune thyroiditis">Autoimmune</a>/chronic
<ul><li><a href="/wiki/Hashimoto%27s_thyroiditis" title="Hashimoto's thyroiditis">Hashimoto's</a></li>
<li><a href="/wiki/Postpartum_thyroiditis" title="Postpartum thyroiditis">Postpartum</a></li>
<li><a href="/wiki/Riedel%27s_thyroiditis" title="Riedel's thyroiditis">Riedel's</a></li></ul></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Enlargement</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Goitre" title="Goitre">Goitre</a>
<ul><li><a href="/wiki/Endemic_goitre" title="Endemic goitre">Endemic goitre</a></li>
<li><a href="/wiki/Toxic_nodular_goiter" class="mw-redirect" title="Toxic nodular goiter">Toxic nodular goiter</a></li>
<li><a href="/wiki/Toxic_multinodular_goiter" class="mw-redirect" title="Toxic multinodular goiter">Toxic multinodular goiter</a></li></ul></li>
<li><a href="/wiki/Thyroid_nodule" title="Thyroid nodule">Thyroid nodule</a>
<ul><li><a href="/wiki/Colloid_nodule" title="Colloid nodule">Colloid nodule</a></li></ul></li></ul>
</div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Hypersensitivity_and_autoimmune_diseases" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Hypersensitivity_disease_by_cause" title="Template:Hypersensitivity disease by cause"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Hypersensitivity_disease_by_cause" title="Template talk:Hypersensitivity disease by cause"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Hypersensitivity_disease_by_cause" title="Special:EditPage/Template:Hypersensitivity disease by cause"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Hypersensitivity_and_autoimmune_diseases" style="font-size:114%;margin:0 4em"><a href="/wiki/Hypersensitivity" title="Hypersensitivity">Hypersensitivity</a> and <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune diseases</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_I_hypersensitivity" title="Type I hypersensitivity">Type I</a>/<a href="/wiki/Allergy" title="Allergy">allergy</a>/<a href="/wiki/Atopy" title="Atopy">atopy</a><br />(<a href="/wiki/Immunoglobulin_E" title="Immunoglobulin E">IgE</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Allergic_asthma" class="mw-redirect" title="Allergic asthma">Allergic asthma</a></li>
<li><a href="/wiki/Allergic_urticaria" class="mw-redirect" title="Allergic urticaria">Allergic urticaria</a></li>
<li><a href="/wiki/Allergic_rhinitis" title="Allergic rhinitis">Allergic rhinitis</a> (Hay fever)</li>
<li><a href="/wiki/Anaphylaxis" title="Anaphylaxis">Anaphylaxis</a></li>
<li><a href="/wiki/Atopic_dermatitis" title="Atopic dermatitis">Atopic dermatitis</a></li>
<li><a href="/wiki/Food_allergy" title="Food allergy">Food allergy</a>
<ul><li>common allergies include: <a href="/wiki/Egg_allergy" title="Egg allergy">Egg</a></li>
<li><a href="/wiki/Milk_allergy" title="Milk allergy">Milk</a></li>
<li><a href="/wiki/Peanut_allergy" title="Peanut allergy">Peanut</a></li>
<li><a href="/wiki/Seafood_allergy" class="mw-redirect" title="Seafood allergy">Seafood</a></li>
<li><a href="/wiki/Soy_allergy" title="Soy allergy">Soy</a></li>
<li><a href="/wiki/Tree_nut_allergy" title="Tree nut allergy">Tree nut</a></li>
<li><a href="/wiki/Wheat_allergy" title="Wheat allergy">Wheat</a></li></ul></li>
<li><a href="/wiki/Side_effects_of_penicillin" title="Side effects of penicillin">Penicillin allergy</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Autoimmune_urticaria" title="Autoimmune urticaria">Autoimmune urticaria</a></li>
<li><a href="/wiki/Eosinophilic_esophagitis" title="Eosinophilic esophagitis">Eosinophilic esophagitis</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_II_hypersensitivity" title="Type II hypersensitivity">Type II</a>/<a href="/wiki/Antibody-dependent_cellular_cytotoxicity" title="Antibody-dependent cellular cytotoxicity">ADCC</a><br />
<ul><li><ul><li><a href="/wiki/Immunoglobulin_G" title="Immunoglobulin G">IgG</a></li>
<li><a href="/wiki/Immunoglobulin_M" title="Immunoglobulin M">IgM</a></li></ul></li></ul></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<li><a href="/wiki/Hemolytic_disease_of_the_newborn" title="Hemolytic disease of the newborn">Hemolytic disease of the newborn</a></li>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cytotoxicity" title="Cytotoxicity">Cytotoxic</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Autoimmune_hemolytic_anemia" title="Autoimmune hemolytic anemia">Autoimmune hemolytic anemia</a></li>
<li><a href="/wiki/Bullous_pemphigoid" title="Bullous pemphigoid">Bullous pemphigoid</a></li>
<li><a href="/wiki/Goodpasture_syndrome" title="Goodpasture syndrome">Goodpasture syndrome</a></li>
<li><a href="/wiki/Guillain%E2%80%93Barr%C3%A9_syndrome" title="Guillain–Barré syndrome">Guillain–Barré syndrome</a></li>
<li><a href="/wiki/Immune_thrombocytopenic_purpura" title="Immune thrombocytopenic purpura">Immune thrombocytopenic purpura</a></li>
<li><a href="/wiki/Pemphigus_vulgaris" title="Pemphigus vulgaris">Pemphigus vulgaris</a></li>
<li><a href="/wiki/Rheumatic_fever" title="Rheumatic fever">Rheumatic fever</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">"<a href="/wiki/Hypersensitivity#Type_V" title="Hypersensitivity">Type V</a>"/<a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a class="mw-selflink selflink">Graves' disease</a></li>
<li><a href="/wiki/Myasthenia_gravis" title="Myasthenia gravis">Myasthenia gravis</a></li>
<li><a href="/wiki/Pernicious_anemia" title="Pernicious anemia">Pernicious anemia</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_III_hypersensitivity" title="Type III hypersensitivity">Type III</a><br />(<a href="/wiki/Immune_complex" title="Immune complex">Immune complex</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Arthus_reaction" title="Arthus reaction">Arthus reaction</a></li>
<li><a href="/wiki/Farmer%27s_lung" title="Farmer's lung">Farmer's lung</a></li>
<li><a href="/wiki/Henoch%E2%80%93Sch%C3%B6nlein_purpura" title="Henoch–Schönlein purpura">Henoch–Schönlein purpura</a></li>
<li><a href="/wiki/Cutaneous_small-vessel_vasculitis" title="Cutaneous small-vessel vasculitis">Hypersensitivity vasculitis</a></li>
<li><a href="/wiki/Acute_proliferative_glomerulonephritis" title="Acute proliferative glomerulonephritis">Post-streptococcal glomerulonephritis</a></li>
<li><a href="/wiki/Reactive_arthritis" title="Reactive arthritis">Reactive arthritis</a></li>
<li><a href="/wiki/Serum_sickness" title="Serum sickness">Serum sickness</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Lupus" title="Lupus">Lupus</a></li>
<li><a href="/wiki/Rheumatoid_arthritis" title="Rheumatoid arthritis">Rheumatoid arthritis</a></li>
<li><a href="/wiki/Subacute_bacterial_endocarditis" title="Subacute bacterial endocarditis">Subacute bacterial endocarditis</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_IV_hypersensitivity" title="Type IV hypersensitivity">Type IV</a>/<a href="/wiki/Cell-mediated_immunity" title="Cell-mediated immunity">cell-mediated</a><br />(<a href="/wiki/T_cell" title="T cell">T cells</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Allergic_contact_dermatitis" title="Allergic contact dermatitis">Allergic contact dermatitis</a></li>
<li><a href="/wiki/Mantoux_test" title="Mantoux test">Mantoux test</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Coeliac_disease" title="Coeliac disease">Coeliac disease</a></li>
<li><a href="/wiki/Giant_cell_arteritis" title="Giant cell arteritis">Giant cell arteritis</a></li>
<li><a href="/wiki/Hashimoto%27s_thyroiditis" title="Hashimoto's thyroiditis">Hashimoto's thyroiditis</a></li>
<li><a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">Multiple sclerosis</a></li>
<li><a href="/wiki/Postorgasmic_illness_syndrome" title="Postorgasmic illness syndrome">Postorgasmic illness syndrome</a></li>
<li><a href="/wiki/Reactive_arthritis" title="Reactive arthritis">Reactive arthritis</a></li>
<li><a href="/wiki/Type_1_diabetes" title="Type 1 diabetes">Type 1 diabetes</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Graft-versus-host_disease" title="Graft-versus-host disease">GVHD</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Transfusion-associated_graft-versus-host_disease" title="Transfusion-associated graft-versus-host disease">Transfusion-associated graft-versus-host disease</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Unknown/<br />multiple</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Foreign</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Hypersensitivity_pneumonitis" title="Hypersensitivity pneumonitis">Hypersensitivity pneumonitis</a>
<ul><li><a href="/wiki/Allergic_bronchopulmonary_aspergillosis" title="Allergic bronchopulmonary aspergillosis">Allergic bronchopulmonary aspergillosis</a></li></ul></li>
<li><a href="/wiki/Latex_allergy" title="Latex allergy">Latex allergy</a> (I+IV)</li>
<li><a href="/wiki/Transplant_rejection" title="Transplant rejection">Transplant rejection</a></li></ul>
</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Autoimmune</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">
<ul><li><a href="/wiki/Addison%27s_disease" title="Addison's disease">Autoimmune adrenalitis</a></li>
<li><a href="/wiki/Autoimmune_hepatitis" title="Autoimmune hepatitis">Autoimmune hepatitis</a></li>
<li><a href="/wiki/Autoimmune_polyendocrine_syndrome" title="Autoimmune polyendocrine syndrome">Autoimmune polyendocrine syndrome</a>
<ul><li><a href="/wiki/Autoimmune_polyendocrine_syndrome_type_1" title="Autoimmune polyendocrine syndrome type 1">APS1</a></li>
<li><a href="/wiki/Autoimmune_polyendocrine_syndrome_type_2" title="Autoimmune polyendocrine syndrome type 2">APS2</a></li></ul></li>
<li><a href="/wiki/Sj%C3%B6gren_syndrome" title="Sjögren syndrome">Sjögren syndrome</a></li>
<li><a href="/wiki/Autoimmune_disease" title="Autoimmune disease">Systemic autoimmune disease</a></li></ul>
</div></td></tr></tbody></table><div></div></td></tr></tbody></table></div>
<div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"><style data-mw-deduplicate="TemplateStyles:r1038841319">.mw-parser-output .tooltip-dotted{border-bottom:1px dotted;cursor:help}</style></div><div role="navigation" class="navbox authority-control" aria-labelledby="Authority_control_databases_frameless&#124;text-top&#124;10px&#124;alt=Edit_this_at_Wikidata&#124;link=https&#58;//www.wikidata.org/wiki/Q16483#identifiers&#124;class=noprint&#124;Edit_this_at_Wikidata" style="padding:3px"><table class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><div id="Authority_control_databases_frameless&#124;text-top&#124;10px&#124;alt=Edit_this_at_Wikidata&#124;link=https&#58;//www.wikidata.org/wiki/Q16483#identifiers&#124;class=noprint&#124;Edit_this_at_Wikidata" style="font-size:114%;margin:0 4em"><a href="/wiki/Help:Authority_control" title="Help:Authority control">Authority control databases</a> <span class="mw-valign-text-top noprint" typeof="mw:File/Frameless"><a href="/wiki/Q16483#identifiers" title="Edit this at Wikidata"><img alt="Edit this at Wikidata" src="/media/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/10px-OOjs_UI_icon_edit-ltr-progressive.svg.png" decoding="async" width="10" height="10" class="mw-file-element" srcset="/media/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/15px-OOjs_UI_icon_edit-ltr-progressive.svg.png 1.5x, /media/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png 2x" data-file-width="20" data-file-height="20" /></a></span></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">International</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><ul><li><span class="uid"><a rel="nofollow" class="external text" href="http://id.worldcat.org/fast/946854/">FAST</a></span></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">National</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"><ul><li><span class="uid"><a rel="nofollow" class="external text" href="https://d-nb.info/gnd/4144092-4">Germany</a></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="https://id.loc.gov/authorities/sh85056549">United States</a></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="https://catalogue.bnf.fr/ark:/12148/cb121242921">France</a></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="https://data.bnf.fr/ark:/12148/cb121242921">BnF data</a></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="https://id.ndl.go.jp/auth/ndlna/00560542">Japan</a></span></li><li><span class="uid"><span class="rt-commentedText tooltip tooltip-dotted" title="Graves-Basedowova nemoc"><a rel="nofollow" class="external text" href="https://aleph.nkp.cz/F/?func=find-c&local_base=aut&ccl_term=ica=ph867751&CON_LNG=ENG">Czech Republic</a></span></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="http://catalogo.bne.es/uhtbin/authoritybrowse.cgi?action=display&authority_id=XX531538">Spain</a></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="http://katalog.nsk.hr/F/?func=direct&doc_number=000092830&local_base=nsk10">Croatia</a></span></li><li><span class="uid"><a rel="nofollow" class="external text" href="http://olduli.nli.org.il/F/?func=find-b&local_base=NLX10&find_code=UID&request=987007538559705171">Israel</a></span></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"><ul><li><span class="uid"><a rel="nofollow" class="external text" href="https://www.idref.fr/029667402">IdRef</a></span></li></ul></div></td></tr></tbody></table></div></div>' |
Whether or not the change was made through a Tor exit node (tor_exit_node) | false |
Unix timestamp of change (timestamp) | '1727864972' |
