View source for Signs and symptoms of Graves' disease

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'''The signs and symptoms of Graves' disease''' generally result from the direct and indirect effects of [[hyperthyroidism]], although they can also be caused by other thyroidal conditions, such as [[Graves' ophthalmopathy]], [[goitre]] and [[pretibial myxedema]]. These clinical manifestations can involve virtually every system in the body.
The mechanisms that mediate these effects are not well understood. The severity of the [[medical sign|signs]] and [[symptom]]s of hyperthyroidism is related to the duration of the disease, the magnitude of the thyroid hormone excess, and the patient's age.
Although the majority of patients experience significant improvement and remission after proper medical care, health care providers should be aware of variability in individual response to hyperthyroidism and individual sensitivity to thyroid hormone fluctuations.<ref name="MyThyroid">{{Cite web|author=Druckerhttp D |title=Hyperthyroidism |url=http://www.mythyroid.com/hyperthyroidism.html |website=MyThyroid.com |year=2005 |access-date=2010-05-03}}</ref> Patients with Graves' disease can also undergo periods of [[hypothyroidism]] (inadequate production of thyroid hormone; see [[hypothyroidism#Symptoms|symptoms of hypothyroidism]]), due to the challenges of finding the right dosage of thyroid hormone suppression and/or supplementation. The body's need for thyroid hormone can also change over time, such as in the first months after radioactive iodine treatment (RAI). Thyroid autoimmune diseases can also be volatile{{Citation needed|date=May 2021}}, as hyperthyroidism can interchange with hypothyroidism and euthyroidism.<ref name="ReferenceB">Psychische stoornissen bij endocriene zieken, 1983, C. van der Meer en W. van Tilburg (red.)</ref>
==General symptoms==
=== Skin/Hair/Nails ===
* [[Pretibial myxedema]]: Waxy, discolored induration of the skin
* Warm and moist skin<ref>Cutaneous manifestations of thyroid disease. Heymann WR, ''J Am Acad Dermatol.'' 1992;26(6) 885.</ref>
* Redness of the elbows is frequently present. It is probably the result of the combination of increased activity, an exposed part, and a hyperirritable [[vasomotor system]].<ref name="ThyroidManager-Ch10-Groot" />
* Thin and fine hair
* Brittle nails
* [[Plummer's nail]]
=== Nose/Sinuses ===
* Chronic [[sinus infections]]
=== Neck ===
* [[Goitre]] (enlarged thyroid): If the thyroid grows large enough, it may compress the [[recurrent laryngeal nerve]], producing [[vocal cord paralysis]], [[dysphonia]], and even respiratory [[stridor]]. Compression of the [[sympathetic chain]] may result in [[Horner's syndrome]].<ref>Surgical management of multinodular goiter with compression symptoms. Ríos A, Rodríguez JM, Canteras M, Galindo PJ, Tebar FJ, Parrilla P, Arch Surg. 2005;140(1) 49; Compression syndromes caused by substernal goitres. Anders HJ, ''Postgrad Med J.'' 1998;74(872) 327.</ref>
=== Eyes ===
* [[Graves' ophthalmopathy]] (protrusion of one or both eyes)
=== Respiratory/Cardiac ===
* [[Dyspnea|Shortness of breath]]<ref name="ThyroidManager-Ch10-Groot" />
* Cardiovascular features may include [[hypertension]], and heart rate that may be [[Tachycardia|rapid]] or [[Heart arrhythmia|irregular in character]]; these may be perceived as [[palpitations]].<ref name="ThyroidManager-Ch10-Groot">"Graves' Disease and the Manifestations of Thyrotoxicosis" – Leslie l. De Groot, Thyroid Disease Manager, Chapter 10 (http://www.thyroidmanager.org/chapter/graves-disease-and-the-manifestations-of-thyrotoxicosis/)</ref> Less common findings include [[high-output heart failure]],<ref>{{cite journal |title=Hyperthyroidism and the Heart |journal=Methodist Debakey Cardiovascular Journal |year=2017 |pmid=28740583 |last1=Osuna |first1=P. M. |last2=Udovcic |first2=M. |last3=Sharma |first3=M. D. |volume=13 |issue=2 |pages=60–63 |doi=10.14797/mdcj-13-2-60 |pmc=5512680 }}</ref> [[left ventricular hypertrophy]], premature atrial and ventricular contractions, [[atrial fibrillation]], [[congestive heart failure]], [[angina]], [[myocardial infarction]], systemic embolization, death from [[Circulatory collapse|cardiovascular collapse]] and resistance to some drug effects ([[digoxin]], [[coumadin]]).<ref name="ThyroidManager-Ch10-Groot" />
=== Gastrointestinal ===
* Gastrointestinal symptoms. This includes [[Pseudodiarrhea|increased bowel movements]], but malabsorption is unusual.<ref name="ThyroidManager-Ch10-Groot" />
=== Musculoskeletal ===
* [[Hyperreflexia]], with a rapid relaxation phase.<ref name="ThyroidManager-Ch10-Groot" />
* [[Tremor]] (usually fine shaking; tremor of the outstretched fingers). In a small study of newly diagnosed hyperthyroid patients, tremor was observed in 76% of them.<ref>{{cite journal |vauthors=Duyff RF, Van den Bosch J, Laman DM, van Loon BJ, Linssen WH |year=2000 |title=Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study |journal=Journal of Neurology, Neurosurgery & Psychiatry |volume=68 |issue=6 |pages=750–755 |doi=10.1136/jnnp.68.6.750 |pmc=1736982 |pmid=10811699}}</ref> Some studies lay the cause for hyperthyroid tremor with a heightened beta-adrenergic state, others suggest an increased metabolism of [[dopamine]].<ref>{{cite journal |vauthors=Henderson JM, Portmann L, Van Melle G, Haller E, Ghika JA |year=1997 |title=Propranolol as an adjunct therapy for hyperthyroid tremor |journal=European Neurology |volume=37 |issue=3 |pages=182–5 |doi=10.1159/000117431 |pmid=9137929}}</ref><ref>{{cite journal |author=Kim HT, Edwards MJ, Lakshmi Narsimhan R, Bhatia |year=2005 |title=a clinical lesson |journal=Parkinsonism & Related Disorders |volume=11 |issue=5 |pages=331–2 |doi=10.1016/j.parkreldis.2005.01.009 |pmid=15970453}}</ref>
* [[Weakness]] or [[muscle weakness]] (especially in the large muscles of the arms and legs). This latter occurs in 60 to 80 percent of patients with untreated hyperthyroidism.<ref>Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. Duyff RF, Van den Bosch J, Laman DM, van Loon BJ, Linssen WH, J Neurol Neurosurg Psychiatry. 2000;68(6) 750; Electromyographic and histological findings in the muscles of patients with thyrotoxicosis. HAVARD CW, CAMPBELL ED, ROSS HB, SPENCE AW, Q J Med. 1963;32:145; Electromyography in thyrotoxicosis. Ramsay ID, Q J Med. 1965;34(135) 255.</ref> Muscle weakness is rarely the chief complaint. The likelihood and degree of muscle weakness is correlated with the duration and severity of the hyperthyroid state, and becomes more likely after the age of 40. Muscle strength returns gradually over several months after the hyperthyroidism has been treated.
* Muscle degeneration
=== Neurologic ===
* A distinctly excessive reaction to all sorts of stimuli.<ref name="ThyroidManager-Ch10-Groot" />
* A marked increase in [[Fatigue (medical)|fatigue]], or [[asthenia]], is often prominent. This increased weariness may be combined with [[hyperactivity]]; patients remark that they are impelled to incessant activity, which, however, causes great fatigue.<ref name="ThyroidManager-Ch10-Groot" />
* Neurological seizures, [[neuropathy]] from nerve entrapment by lesions of pretibial myxedema, and [[hypokalemic periodic paralysis]] may occur.<ref name="ThyroidManager-Ch10-Groot" /> [[Athetoid]], [[Choreia (disease)|choreia]], and [[Corticospinal tract#Corticospinal tract damage|corticospinal tract damage]], are rare. An acute thyrotoxic [[encephalopathy]] is very rare.<ref name="ThyroidManager-Ch10-Groot" />
=== Endocrine ===
* [[Weight loss]] despite normal or increased appetite. Some patients (especially younger ones) ''gain'' weight due to excessive appetite stimulation that exceeds the weight loss effect.<ref name="ReferenceC">{{cite journal |author=Nordyke RA, Gilbert FI Jr, Harada AS |year=1988 |title=Graves' disease. Influence of age on clinical findings |journal=Arch Intern Med |volume=148 |issue=3 |pages=626–31 |doi=10.1001/archinte.1988.00380030132023 |pmid=3341864}}</ref>
* [[Polyphagia|Increased appetite]].<ref name="ThyroidManager-Ch10-Groot" />
* [[Hyperhidrosis|Increased sweating]]<ref name="ReferenceC" />
* [[Heat intolerance]]<ref name="ReferenceC" />
* [[Gynecomastia|Abnormal breast enlargement in men]]<ref>The hypothalamic-pituitary-testicular axis in thyrotoxicosis. Kidd GS, Glass AR, Vigersky RA, J Clin Endocrinol Metab. 1979;48(5) 798.</ref>
* Augmented calcium levels in the blood (by as much as 25% – known as [[hypercalcaemia]]). This can cause stomach upset, excessive urination, and impaired kidney function.<ref name="medicinenet">{{Cite web |last=Mathur |first=Ruchi |date=2014-12-01 |title=Thyroid Disease, Osteoporosis, and Calcium |url=http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |access-date=2017-10-07 |publisher=MedicineNet}}</ref>
* [[Diabetes]] may be activated or intensified, and its control worsened. The diabetes is ameliorated or may disappear when the thyrotoxicosis is treated.<ref name="ThyroidManager-Ch10-Groot" />
* Reproductive symptoms in men may include reduced free [[testosterone]] (due to the elevation of testosterone-estrogen binding globulin level),<ref name="ThyroidManager-Ch10-Groot" /> diminished [[libido]], [[erectile dysfunction]] and (reversible) impaired sperm production with lower mean sperm density, a high incidence of sperm abnormalities, and reduced mobility of the sperm cells.<ref name="ThyroidManager-Ch10-Groot" />
* Women may experience [[oligomenorrhea|infrequent menstruation]] or [[amenorrhea|irregular and scant menstrual flow]] along with difficulty conceiving, [[infertility]] and recurrent [[miscarriage]].<ref>{{cite journal |author-link1=Norbert Gleicher |vauthors=Gleicher N, Weghofer A, Barad DH |date=Apr 2011 |title=Do chromosomally abnormal pregnancies really preclude autoimmune etiologies of spontaneous miscarriages? |journal=Autoimmunity Reviews |volume=10 |issue=6 |pages=361–3 |doi=10.1016/j.autrev.2010.12.004 |pmid=21195806}}</ref><ref>{{cite journal |author=Gleicher N |date=December 2010 |title=Does the immune system induce labor? Lessons from preterm deliveries in women with autoimmune diseases |journal=Clinical Reviews in Allergy & Immunology |volume=39 |issue=3 |pages=194–206 |doi=10.1007/s12016-009-8180-8 |pmid=19844811 |s2cid=37559462}}</ref>
=== Psychiatric ===
* [[Insomnia]]<ref>A survey study of neuropsychiatric complaints in patients with Graves' disease. Stern RA, Robinson B, Thorner AR, Arruda JE, Prohaska ML, Prange AJ Jr, ''J Neuropsychiatry Clin Neurosci.'' 1996;8(2) 181.</ref>
=== Other ===
* Evidence of mild or severe liver disease may be found.<ref name="ThyroidManager-Ch10-Groot" />
==Effects on the skeleton==
Overt hyperthyroidism caused by Grave's Disease is associated with accelerated [[bone remodeling]] (resulting in increased porosity of [[cortical bone]] and reduced volume of [[trabecular bone]]). This can lead to reduced [[bone density]] and eventually [[osteoporosis]] as well as increased [[Bone fracture|fracture]] rates. The increased hip fracture rates later in life in turn cause excess late mortality.{{Citation needed|date=April 2022}} The changes in bone metabolism are connected with negative [[Bone#Calcium balance|calcium balance]], an increased excretion of [[Calcium in biology|calcium]] and [[Phosphorus#Biological role|phosphorus]] in the urine ([[hypercalciuria]]) and stool, and, rarely, [[hypercalcemia]].<ref name="medicinenet"/> In [[hyperthyroidism]], the normal cycle duration of [[bone resorption]] of approximately 200 days is halved, and each cycle is associated with a 9.6 percent loss of mineralized [[Mineralized tissues#Bone|bone]]. In [[hypothyroidism]], cycle length approximates 700 days and is associated with a 17 percent increase in mineralized bone.<ref>Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Eriksen EF, Endocr Rev. 1986;7(4) 379.</ref>
The extent of the reduction in bone density in most studies is 10–20%. The clinical manifestations on bone differ depending on the age of the patient. [[menopause#Postmenopause|Postmenopausal woman]] are most sensitive to accelerated bone loss from thyrotoxicosis. Accelerated bone growth in growing children can increase [[ossification]] in the short term, but generally results in short-stature adults compared with the predicted heights.{{citation needed|date=August 2020}}
If thyrotoxicosis is treated early, bone loss can be minimized.<ref name="medicinenet" /> The level of calcium in the blood can be determined by a simple blood test, and a [[dual energy X-ray absorptiometry|Dual Energy X-Ray Absorptiometry scan]] can help determine patient bone density relative to the rest of the population. There are many medications that can help to rebuild bone mass and to prevent further bone loss, such as [[Bisphosphonate]]s.<ref name="medicinenet" /> [[Risedronate]] treatment has been demonstrated to help restore bone mass in [[osteopenia]]/[[osteoporosis]] associated with Graves' disease.<ref name="ThyroidManager-Ch11-Groot">Chapter 11. Diagnosis and Treatment of Graves' Disease Leslie J. De Groot, MD Professor of Medicine – http://www.thyroidmanager.org/chapter/diagnosis-and-treatment-of-graves-disease/ Updated: March 5, 2008</ref> Nevertheless, weight-bearing [[exercises]], a [[balanced diet]], calcium intake of about 1500&nbsp;mg a day and enough [[vitamin D]], are of course elementary foundations.<ref name="medicinenet" />
==Eye symptoms==
Hyperthyroidism almost always causes general eye symptoms like dryness and irritation, regardless of what the cause of the hyperthyroid state is. However, these need to be distinguished from [[Graves' ophthalmopathy]], which can only occur in patients who have Graves' disease. (It may also, rarely, be seen in [[Hashimoto's thyroiditis]], primary [[hypothyroidism]], and [[thyroid cancer]]).<ref>{{Cite journal |last1=Şahlı |first1=Esra |last2=Gündüz |first2=Kaan |date=April 2017 |title=Thyroid-associated Ophthalmopathy |journal=Turkish Journal of Ophthalmology |volume=47 |issue=2 |pages=94–105 |doi=10.4274/tjo.80688 |issn=2149-8695 |pmc=5384127 |pmid=28405484}}</ref>
About 20–25% of patients with Graves' disease will suffer from clinically obvious Graves' ophthalmopathy, and not just from the eye signs of hyperthyroidism. Only 3 to 5% will develop severe ophthalmopathy.<ref>Graves' ophthalmopathy: a preventable disease? Luigi Bartalena, Claudio Marcocci and Aldo Pinchera1 – European Journal of Endocrinology (2002) 146 457–461</ref> However, when subjected to closer inspection (e.g. by [[magnetic resonance imaging]] of the [[Orbit (anatomy)|orbits]]) many more patients have evidence of ophthalmopathy. It is estimated that for every 100,000 persons, 16 women and 3 men have Graves' ophthalmopathy every year.<ref>{{cite journal |vauthors=Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup DM, Garrity JA, Gorman CA | year = 1995 | title = The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota | journal = American Journal of Ophthalmology| volume = 120 | issue = 4| pages = 511–7 | doi=10.1016/s0002-9394(14)72666-2| pmid = 7573310 }}</ref>
Although it is true that in most patients ophthalmopathy, goiter, and symptoms of thyrotoxicosis appear more or less coincidentally, it is also true that in certain cases eye signs may appear long before thyrotoxicosis is evident, or become worse when the thyrotoxicosis is subsiding or has been controlled by treatment.<ref name="ThyroidManager-Ch10-Groot"/> In approximately 20% of ophthalmopathy patients, ophthalmopathy appears before the onset of hyperthyroidism, in about 40% concurrently, and in about 20% in the six months after diagnosis.<ref>{{cite journal |vauthors=Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup DM, Garrity JA, Gorman CA | year = 1996 | title = Chronology of Graves' ophthalmopathy in an incidence cohort | journal = American Journal of Ophthalmology| volume = 121 | issue = 4| pages = 426–34 | doi = 10.1016/S0002-9394(14)70439-8 | pmid = 8604736 }}</ref> In the remainder, the eye disease first becomes apparent after treatment of the hyperthyroidism, more often in patients treated with radioiodine.<ref>{{cite journal |vauthors=Tallstedt L, Lundell G, Tørring O, Wallin G, Ljunggren JG, Blomgren H, Taube A | year = 1992 | title = Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism | journal = New England Journal of Medicine| volume = 326 | issue = 26| pages = 1733–8 | doi=10.1056/nejm199206253262603| pmid = 1489388 | doi-access = free }}</ref>
It can sometimes be difficult to distinguish between eye symptoms due to hyperthyroidism and those due to Graves' antibodies, because the two often occur coincidentally. What can make things particularly difficult, is that many patients with hyperthyroidism have lid retraction, which leads to stare and lid lag (due to contraction of the [[levator palpebrae]] muscles of the eyelids). This stare may then give the ''appearance'' of protruding eyeballs ([[proptosis]]), when none in fact exists. This subsides when the hyperthyroidism is treated.{{citation needed|date=August 2020}}
===Due to Graves' ophthalmopathy===
{{Main|Graves' ophthalmopathy}}[[Image:Proptosis and lid retraction from Graves' Disease.jpg|thumb|right|200px|Photo showing the classic finding of proptosis and lid retraction in Graves' disease]]
Graves' ophthalmopathy is characterized by inflammation of the [[extraocular muscles]], orbital fat and connective tissue. It results in the following signs, which can be extremely distressing to the patient:<ref name="ThyroidManager-Ch10-Groot"/>
* Most frequent are symptoms due to [[conjunctival]] or [[cornea]]l irritation: burning, [[photophobia]], tearing, pain, and a gritty or sandy sensation.<ref name="ThyroidManager-Ch10-Groot"/>
* Protruding eyeballs (known as [[proptosis]] and [[exophthalmos]]).
* [[Diplopia]] (double vision) is common.<ref name="ThyroidManager-Ch10-Groot"/>
* Limitation of eye movement (due to impairment of [[eye muscle]] function).
* Periorbital and conjunctival [[edema]] (accumulation of fluid beneath the skin around the eyes).
* In severe cases, the [[optic nerve]] may be compressed and acuity of vision impaired.<ref name="pmid19547630">{{Cite journal|author=Ponto KA, Pitz S, Pfeiffer N, Hommel G, Weber MM, Kahaly GJ |title=Quality of life and occupational disability in endocrine orbitopathy |journal=Deutsches Ärzteblatt Online|volume=106 |issue=17 |pages=283–9 |date=April 2009 |pmid=19547630 |pmc=2689575 |doi=10.3238/arztebl.2009.0283 |last2=Pitz |last3=Pfeiffer |last4=Hommel |last5=Weber |last6=Kahaly }}</ref>
* Occasionally [[loss of vision]].
===Due to hyperthyroidism===
In the absence of Graves' ophthalmopathy, patients may demonstrate other ophthalmic symptoms and signs due to hyperthyroidism:
* Dry eyes (due to loss of corneal moisture).<ref name="pmid19547630"/>
* A sense of irritation, discomfort, or pain in the eyes.
* A tingling sensation behind the eyes or the feeling of grit or sand in the eyes.
* Excessive tearing that is often made worse by exposure to cold air, wind, or bright lights.
* Swelling or redness of the eyes.
* Stare
* Lid lag ([[Von Graefe's sign]])
* [[Sensitivity to light]]
* Blurring of vision
* Widened [[palpebral fissures]]
* Infrequent blinking
* The appearance of lid retraction.
==Neuropsychological manifestations==
Several studies have suggested a high prevalence of [[neuropsychiatric disorder]]s and [[mental disorder]] symptoms in Graves' disease (and thyroid disease in general), which are similar to those in patients with organic brain disease.<ref name="pmid17044727">{{Cite journal|author=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|last2=Prange Jr |s2cid=20003511 }}</ref><ref>{{Cite journal| doi = 10.1159/000026545 | title = Prevalence of Psychiatric Disorders in Thyroid Diseased Patients | author = G.P.A. Placidia, M. Boldrinia, A. Patronellia, E. Fioreb, L. Chiovatob, G. Perugia, D. Marazzitia | journal = Neuropsychobiology| year = 1998 | volume = 38 | pages = 222–5 | pmid = 9813461 | issue = 4| last2 = Boldrini | last3 = Patronelli | last4 = Fiore | last5 = Chiovato | last6 = Perugi | last7 = Marazziti | hdl = 2158/789562 | s2cid = 25689764 | hdl-access = free }}</ref><ref name="pmid9081554">{{Cite journal|author=Stern RA, Robinson B, Thorner AR, Arruda JE, Prohaska ML, Prange AJ |title=A survey study of neuropsychiatric complaints in patients with Graves' disease |journal=The Journal of Neuropsychiatry and Clinical Neurosciences|volume=8 |issue=2 |pages=181–5 |year=1996 |pmid=9081554 |doi= 10.1176/jnp.8.2.181|last2=Robinson |last3=Thorner |last4=Arruda |last5=Prohaska |last6=Prange Jr }}</ref><ref>{{Cite journal| title = Thyroid hormones, the brain, and affective disorders| author =  Joffe RT, Sokolov ST. | journal = Critical Reviews in Neurobiology| year = 1994 | volume = 8 | issue = 1–2 | pages = 45–63 | pmid = 8124730| last2 =  Sokolov }}</ref><ref>{{Cite journal| title = Attention disturbance in graves' disease | author =  Alvarez | journal =  Psychoneuroendocrinology| year = 1983 | volume = 8 | issue = 4 | pages = 451–4 | pmid = 6689536 | last2 = Gómez | first2 = A | last3 = Alavez | first3 = E | last4 = Navarro | first4 = D | doi=10.1016/0306-4530(83)90026-4| s2cid = 19460006 }}</ref> These manifestations are diverse, affecting the [[Central nervous system|central]] and [[peripheral nervous system|peripheral]] nervous systems. The vast majority of patients with hyperthyroidism meet criteria for some psychiatric disorders,<ref name="pmid17044727"/> and those with milder presentations are probably not entirely free of mental symptoms such as emotional lability, tension, depression and anxiety.<ref name="pmid17044727"/> Anxiety syndromes related to hyperthyroidism are typically complicated by major depression and cognitive decline, such as in memory and attention.<ref>{{cite journal | doi = 10.1016/0163-8343(88)90084-9 | last1 = Trzepacz | first1 = PT | last2 = McCue | first2 = M | last3 = Klein | first3 = I |name-list-style=vanc | last4 = Levey | year = 1988 | first4 = GS | last5 = Greenhouse | first5 = J | title = A psychiatric and neuropsychological study of patients with untreated Graves' disease | journal = General Hospital Psychiatry| volume = 10 | issue = 1| pages = 49–55 | pmid = 3345907 }}</ref> Some studies contradict the psychological findings. For example, a large 2002 study found "no statistical association between thyroid dysfunction, and the presence of depression or anxiety disorder."<ref name="pmid12100345">{{Cite journal|author=Engum A, Bjøro T, Mykletun A, Dahl AA |title=An association between depression, anxiety and thyroid function--a clinical fact or an artifact?|journal=Acta Psychiatrica Scandinavica|volume=106 |issue=1 |pages=27–34 |date=July 2002|pmid=12100345 |doi= 10.1034/j.1600-0447.2002.01250.x|last2=Bjøro|last3=Mykletun|last4=Dahl|s2cid=46316229}}</ref> In one study on hospitalised elderly patients, over half had cognitive impairment with either dementia or confusion.<ref name="pmid8604186">{{Cite journal|author=Martin FI, Deam DR |title=Hyperthyroidism in elderly hospitalised patients. Clinical features and treatment outcomes |journal=Medical Journal of Australia|volume=164 |issue=4 |pages=200–3 |date=February 1996 |pmid=8604186 |doi= 10.5694/j.1326-5377.1996.tb94135.x|last2=Deam |s2cid=29800258 }}</ref> However, a controlled study on 31 Graves' disease patients found that while patients had subjective reports of cognitive deficits in the toxic phase of Graves' thyrotoxicosis, formal testing found no cognitive impairment and suggested the reported symptoms may reflect the affective and somatic manifestations of hyperthyroidism.<ref name="pmid17097812">{{Cite journal|author=Vogel A |title=Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis |journal=Psychoneuroendocrinology|volume=32 |issue=1 |pages=36–43 |date=January 2007 |pmid=17097812 |doi=10.1016/j.psyneuen.2006.09.012 |name-list-style=vanc|author2=Elberling TV|author3=Hørding M|display-authors=3|last4=Dock|first4=J|last5=Rasmussen|first5=A|last6=Feldtrasmussen|first6=U|last7=Perrild|first7=H|last8=Waldemar|first8=G|s2cid=54416080 }}</ref> Notably, a literature review of 2006 notes [[methodology]] issues in the consistency of Graves' disease [[diagnostic criteria]], which might explain the apparently contradicting findings. These researchers found many reports about residual complaints in patients who were euthyroid after treatment, with a high prevalence of [[anxiety disorders]] and [[bipolar disorder]], as well as elevated scores on scales of [[anxiety]], [[Depression (mood)|depression]] and psychological distress.<ref name="pmid17044727"/> In a 1992 study, a significant proportion of the 137 questioned patients with Graves' disease reported – among other things – increased crying (55%), being easily startled (53%), being tired all the time (47%), a significant decrease in social activity (46%), feelings of being out of control (45%), feelings of hopelessness (43%), loss of sense of humor (41%), loss of interest in things they formerly enjoyed (39%), not being able to 'connect' with others (34%).<ref>Journal of Neuropsychiatry and clinical neurosciences, 1996, 8:181–185.</ref>
Several studies point out that the severity of psychiatric symptoms could easily result in an inappropriate referral to a psychiatrist prior to the diagnosis of hyperthyroidism.<ref name="pmid3345907">{{Cite journal|author=Trzepacz PT, McCue M, Klein I, Levey GS, Greenhouse J |title=A psychiatric and neuropsychological study of patients with untreated Graves' disease |journal=General Hospital Psychiatry|volume=10 |issue=1 |pages=49–55 |date=January 1988 |pmid=3345907 |doi= 10.1016/0163-8343(88)90084-9|last2=McCue |last3=Klein |last4=Levey |last5=Greenhouse }}</ref><ref name="pmid6687506">{{Cite journal|author=McGaffee J, Lippmann S, Barnes MA |title=Psychiatric presentations of hyperthyroidism |journal=American Family Physician|volume=27 |issue=2 |pages=257–60 |date=February 1983 |pmid=6687506 |last2=Lippmann |last3=Barnes }}</ref> Consequently, undiagnosed hyperthyroidism sometimes results in inappropriate use of psychotropic medications; prompt recognition of hyperthyroidism (or hypothyroidism) through thyroid function screening is therefore recommended in the evaluation of patients with psychiatric symptoms.<ref name="pmid6687506"/><ref name="pmid8033020">{{Cite journal|author=Steinberg PI |title=A case of paranoid disorder associated with hyperthyroidism |journal=The Canadian Journal of Psychiatry|volume=39 |issue=3 |pages=153–6 |date=April 1994 |pmid=8033020 |doi= 10.1177/070674379403900306|s2cid=34764148 }}</ref> Naturally, the management of patients would be improved by collaboration between an [[endocrinologist]] and a [[psychiatrist]].<ref>Psychiatric Manifestations of Graves' Hyperthyroidism Pathophysiology and Treatment Options Robertas Bunevicius and Arthur J. Prange Jr – CNS Drugs. 2006;20(11) 897–909</ref>
Overall, reported symptoms vary from mild to severe aspects of anxiety or depression, and may include psychotic and behavioral disturbances:
* Varying degrees of [[anxiety]],<ref name="pmid9081554"/> such as a very active mind,<ref name="ThyroidManager-Ch10-Groot"/> [[irritability]],<ref name="pmid9081554"/> [[hyperactivity]], [[Psychomotor agitation|agitation]], restlessness, [[Anxiety|nervousness]], distractible hyperactivity<ref name="ReferenceA">{{Cite journal|author=Awad AG|title=The Thyroid and the Mind and Emotions/Thyroid Dysfunction and Mental Disorders |url=http://www.thyroid.ca/e10f.php |journal=Thyrobulletin|volume=7 |year=2000 |access-date=2010-05-06 |issue=3}}</ref> and [[panic attacks]].<ref name="pmid9813461">{{Cite journal|author=Placidi GP |title=Prevalence of psychiatric disorders in thyroid diseased patients |journal=Neuropsychobiology|volume=38 |issue=4 |pages=222–5 |date=November 1998 |pmid=9813461 |doi= 10.1159/000026545|name-list-style=vanc|author2=Boldrini M|author3=Patronelli A|display-authors=3|last4=Fiore|first4=E.|last5=Chiovato|first5=L.|last6=Perugi|first6=G.|last7=Marazziti|first7=D.|hdl=2158/789562 |s2cid=25689764 |hdl-access=free}}</ref> In addition patients may experience vivid dreams and, occasionally, [[nightmares]].
* Depressive features of mental impairment, memory lapses,<ref name="pmid9081554"/> diminished attention span,<ref name="pmid9081554"/> fluctuating depression.<ref name="ReferenceA"/><ref>Psychische stoornissen bij endocriene zieken, 1983, C. van der Meer en W. van Tilburg (red.) suggests usually with an agitated streak, not a depression of the inhibited type</ref>
* [[Labile affect|Emotional lability]] and in some patients [[hypomania]].<ref name="pmid15763125">{{Cite journal|author=Bunevicius R, Velickiene D, Prange AJ |title=Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease |journal=General Hospital Psychiatry|volume=27 |issue=2|pages=133–9 |year=2005 |pmid=15763125 |doi=10.1016/j.genhosppsych.2004.10.002 |last2=Velickiene |last3=Prange Jr }}</ref>
* The pathological well-being ([[euphoria]]) or hyperactivity may produce a state of exhaustion, and profound fatigue or [[asthenia]] chiefly characterizes the picture.<ref name="ThyroidManager-Ch10-Groot"/>
* Erratic behaviour may include [[Intermittent explosive disorder|intermittent rage disorder]] and mild attention deficit disorder.<ref>The Thyroid Solution, Arem Ridha</ref> Some patients become hyperirritable and combative, which can precipitate accidents or even assaultive behaviour.<ref name="ThyroidManager-Ch10-Groot"/>
* In more extreme cases features of [[psychosis]],<ref name="pmid6338551">{{Cite journal|author=Hall RC |title=Psychiatric effects of thyroid hormone disturbance |journal=Psychosomatics|volume=24 |issue=1 |pages=7–11, 15–8 |date=January 1983 |pmid=6338551 |doi= 10.1016/S0033-3182(83)73255-X}}</ref> with [[delusions of persecution]] or [[delusions of reference]],<ref name="pmid3074208">{{Cite journal|author=Mizukami K, Shiraishi H, Koizumi J |title=A Graves' disease of identical twins with mental disorder |journal=Japanese Journal of Psychiatry and Neurology|volume=42 |issue=4 |pages=777–83 |date=December 1988 |pmid=3074208 |doi= 10.1111/j.1440-1819.1988.tb01166.x|last2=Shiraishi |last3=Koizumi |s2cid=35971791 }}</ref> and [[pressure of speech]] may present themselves. Rarely, patients develop visual or auditory [[hallucinations]] or a frank psychosis,<ref name="ThyroidManager-Ch10-Groot"/> and may appear [[schizophrenia|schizophrenic]], lose touch with reality and become delirious,<ref name="ReferenceB"/><ref name="ReferenceA"/> Such psychotic symptoms may not completely clear up after the hyperthyroidism has been treated.<ref name="ThyroidManager-Ch10-Groot"/> Paranoia and paranoid-hallucinatory psychosis in hyperthyroidism usually have a manic disposition and it is therefore often not clear if the patient is experiencing a paranoid psychosis with depressive streaks, or a depression that has paranoid streaks.<ref name="ReferenceB"/>
Treatment of hyperthyroidism typically leads to improvement in cognitive and behavioral impairments.<ref name="pmid17097812"/> Agitation, inattention, and frontal lobe impairment may improve more rapidly than other cognitive functions. However, several studies confirm that a substantial proportion of patients with hyperthyroidism have psychiatric disorders or mental symptoms and decreased quality of life even after successful treatment of their hyperthyroidism.<ref name="pmid9081554"/>
===Effects on pre-existing psychiatric disorders===
Patients with pre-existing psychiatric disorders, will experience a worsening of their usual symptoms, as observed by several studies. A study of 1999 found that Graves' disease exacerbated the symptoms of [[Tourette's disorder]] and [[attention-deficit hyperactivity disorder]] (ADHD), and points out that the lack of diagnosis of the Graves' disease compromised the efficacy of the treatment of these disorders.<ref name="pmid10405504">{{Cite journal|author=Woolston JL, Caracansi A |title=Case study: missed diagnosis and mistreatment of unrecognized comorbid Graves disease |journal=Journal of the American Academy of Child & Adolescent Psychiatry|volume=38 |issue=7 |pages=861–4 |date=July 1999 |pmid=10405504 |doi= 10.1097/00004583-199907000-00016|last2=Caracansi |doi-access=free }}</ref> Patients who are known to have a convulsive disorder may become more difficult to control with the usual medications, and seizures may appear in patients who have never previously manifested such symptoms.<ref name="ThyroidManager-Ch10-Groot"/>
==Sub-clinical hyperthyroidism==
In sub-clinical hyperthyroidism, serum [[Thyroid-stimulating hormone|TSH]] is abnormally low, but T4- and T3-levels fall within laboratory reference ranges.<ref>Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease Stig Andersen, Klaus Michael Pedersen, Niels Henrik Bruun and Peter Laurberg – The Journal of Clinical Endocrinology & Metabolism, 2007, Vol. 87, No. 3 1068–1072</ref> It primarily affects the [[skeleton]] and the cardiovascular system (abnormalities in other systems have also been reported), in a similar but less severe and less frequent way than overt [[hyperthyroidism]] does. It can alter cardiac function, with [[increased heart rate]], increased [[left ventricular]] mass index, increased [[cardiac contractility]], [[diastolic dysfunction]], and induction of [[arrhythmias|ectopic atrial beats]]. Long-term mild excess of thyroid hormone can thus cause impaired [[cardiac reserve]] and exercise capacity.<ref name="ThyroidManager-Ch10-Groot"/> In a large population-based study of 2008, the odds of having poorer [[cognitive function]] were greater for sub-clinical hyperthyroidism than for [[stroke]], [[diabetes mellitus]], and [[Parkinson's disease]].<ref name="pmid19054181">{{Cite journal|author=Ceresini G |title=Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study |journal=Journal of the American Geriatrics Society|volume=57 |issue=1 |pages=89–93 |date=January 2009 |pmid=19054181 |pmc=2631617 |doi=10.1111/j.1532-5415.2008.02080.x |name-list-style=vanc|author2=Lauretani F|author3=Maggio M|display-authors=3|last4=Ceda|first4=Gian Paolo|last5=Morganti|first5=Simonetta|last6=Usberti|first6=Elisa|last7=Chezzi|first7=Carlo|last8=Valcavi|first8=Rita|last9=Bandinelli|first9=Stefania|citeseerx=10.1.1.657.1067}}</ref> Sub-clinical hyperthyroidism might modestly increase the risk of cognitive impairment and dementia.<ref>{{cite journal|last1=Rieben|first1=Carole|last2=Segna|first2=Daniel|last3=da Costa|first3=Bruno R.|last4=Collet|first4=Tinh-Hai|last5=Chaker|first5=Layal|last6=Aubert|first6=Carole E.|last7=Baumgartner|first7=Christine|last8=Almeida|first8=Osvaldo P.|last9=Hogervorst|first9=Eef|last10=Trompet|first10=Stella|last11=Masaki|first11=Kamal|last12=Mooijaart|first12=Simon P.|last13=Gussekloo|first13=Jacobijn|last14=Peeters|first14=Robin P.|last15=Bauer|first15=Douglas C.|last16=Aujesky|first16=Drahomir|last17=Rodondi|first17=Nicolas|title=Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies|journal=The Journal of Clinical Endocrinology & Metabolism|volume=101|issue=12|date=30 September 2016|pages=jc.2016–2129|doi=10.1210/jc.2016-2129|pmid=27689250|pmc=6287525}}</ref> Subclinical hyperthyroidism in pregnancy is associated with an increased risk of [[pre-eclampsia]], [[low birth weight]], [[miscarriage]] and [[preterm birth]].<ref name="Lee 2023">{{cite journal |last1=Lee |first1=Sun Y. |last2=Pearce |first2=Elizabeth N. |title=Hyperthyroidism: A Review |journal=JAMA |date=17 October 2023 |volume=330 |issue=15 |pages=1472 |doi=10.1001/jama.2023.19052|pmc=10873132 }}</ref> [[Propylthiouracil]] is the preferred treatment of hyperthyroidism (both overt and subclinical) in the first trimester of pregnancy as it is associated with less birth defects than [[methimazole]].<ref name="Lee 2023" />
A possible explanation for the mental symptoms of sub-clinical thyroid disease, might be found in the fact that the brain has among the highest expression of THR's{{Clarify|reason=Thyroid Hormone Receptor?|date=September 2018}}, and that neurons are often more sensitive than other tissues to thyroid abnormalities, including sub-clinical hyperthyroidism and thyrotoxicosis.<ref>{{cite journal | doi = 10.1210/mend-3-2-392 | last1 = Sakurai | first1 = A |name-list-style=vanc | last2 = Nakai | first2 = A| year = 1989 | last3 = Degroot | first3 = LJ | title = Expression of three forms of thyroid hormone receptor in human tissues | journal = Molecular Endocrinology| volume = 3 | issue = 2| pages = 392–9 | pmid = 2710139 | doi-access = free }}</ref><ref>{{cite journal | last1 = Shahrara | first1 = S | last2 = Drvota | first2 = V | last3 = Sylven | first3 = C. |name-list-style=vanc | year = 1999 | title = Organ specific expression of thyroid hormone receptor mRNA and protein in different human tissues | journal = Biological & Pharmaceutical Bulletin| volume = 22 | issue = 10| pages = 1027–33 | pmid = 10549850 | doi = 10.1248/bpb.22.1027 | doi-access = free }}</ref><ref>{{cite journal | last1 = Geracioti | first1 = TD Jr |name-list-style=vanc | year = 2006 | title = How to identify hypothyroidism's psychiatric presentations | journal =Current Psychiatry | volume = 5 | issue = 11| pages = 98–117 }}</ref> In a 1996 survey study respondents reported a significant decline in memory, attention, planning, and overall productivity from the period 2 years prior to Graves' symptoms onset to the period when hyperthyroid.<ref name="pmid9081554"/> Also, hypersensitivity of the [[central nervous system]] to low-grade hyperthyroidism can result in an [[anxiety disorder]] before other Graves' disease symptoms emerge. E.g., [[panic disorder]] has been reported to precede Graves' hyperthyroidism by 4 to 5 years in some cases, although it is not known how frequently this occurs.<ref>{{cite journal | doi = 10.1159/000289088 | last1 = Matsubayashi | first1 = S | last2 = Tamai | first2 = H | last3 = Matsumoto | first3 = Y |name-list-style=vanc  | last4 = Tamagawa| year = 1996 | first4 = K | last5 = Mukuta | first5 = T | last6 = Morita | first6 = T | last7 = Kubo | first7 = C | title = Graves' disease after the onset of panic disorder | journal = Psychotherapy and Psychosomatics| volume = 65 | issue = 5| pages = 277–80 | pmid = 8893330 }}</ref>
However, while clinical hyperthyroidism is associated with frank [[Graves' disease#Neuropsychological manifestations|neuropsychological and affective alterations]], the occurrence of these alterations and their treatment in mild and sub-clinical hyperthyroidism remains a controversial issue. Regardless of the inconsistent findings, a 2007 study by Andersen et al. states that the distinction between sub-clinical and overt thyroid disease is in any case somewhat arbitrary.<ref name="pmid11889165">{{Cite journal|author=Andersen S, Pedersen KM, Bruun NH, Laurberg P |title=Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease |journal=The Journal of Clinical Endocrinology and Metabolism|volume=87 |issue=3 |pages=1068–72 |date=March 2002 |pmid=11889165 |doi= 10.1210/jc.87.3.1068|url=http://jcem.endojournals.org/cgi/content/full/87/3/1068|last2=Pedersen |last3=Bruun |last4=Laurberg |doi-access=free }}</ref> Sub-clinical hyperthyroidism has been reported in 63% of euthyroid Graves' disease,<ref>Studies on thyrotrophin receptor antibodies in patients with euthyroid Graves' disease. Kasagi K, Hatabu H, Tokuda Y, Iida Y, Endo K, Konishi J, Clin Endocrinol. 1988;29(4) 357.</ref> but only in 4% of cases where Graves' disease was in remission.<ref>Studies of thyroid function and immune parameters in patients with hyperthyroid Graves' disease in remission. Murakami M, Koizumi Y, Aizawa T, Yamada T, Takahashi Y, Watanabe T, Kamoi K, The Journal of Clinical Endocrinology and Metabolism 1988;66(1) 103.</ref>
Subclinical hyperthyroidism has an 8% risk of converting to overt hyperthyroidism at 1 year, and a 26% risk at 5 years.<ref name="Lee 2023" />
==Children and adolescents==
Hyperthyroidism has unique effects in children on growth and pubertal development, e.g. causing [[Epiphyseal plate|epiphyseal]] maturation. In growing children, accelerated bone growth from hyperthyroidism can increase [[osteogenesis]] in the short term, but generally results in short-stature adults compared with the predicted heights. Pubertal development tends to be delayed, or slowed. Girls who have undergone [[menarche]] may develop secondary [[amenorrhea]]. Hyperthyroidism is associated with high sex hormone-binding globulin ([[SHBG]]), which may result in high serum [[estradiol]] levels in girls and [[testosterone]] levels in boys. However, unbound or free levels of these hormones are decreased. Hyperthyroidism before the age of four may cause neurodevelopmental delay. A study by Segni et al. suggests that permanent [[brain damage]] can occur as a result of the illness.<ref name="ThyroidManager-Ch10-Groot"/><ref>{{Cite journal| author = Segni M, Leonardi E, Mazzoncini B, Pucarelli I, Pasquino AM | title = Special features of Graves' disease in early childhood | journal = Thyroid| volume = 9 | year = 1999 | pmid = 10524565 | issue = 9| pages = 871–7|doi=10.1089/thy.1999.9.871| last2 = Leonardi | last3 = Mazzoncini | last4 = Pucarelli | last5 = Pasquino }}</ref>
Ophthalmopatic findings are more common but less severe in children (severe infiltrative exophthalmos is virtually unknown before mid-adolescence), but besides that, many of the typical clinical features of hyperthyroidism in children and adolescents are similar to those in adults.<ref name="ThyroidManager-Ch10-Groot"/> An important difference between children and adults with Graves' disease, is that children have not yet developed like adults have (psychological and physiological), and that they are a lot more dependent on their environment. The [[encephalopathy]] will have profound effects on children's developing personalities and developing relationship with their environment. Disturbments in bodily development further complicates matters. The consequences for the development and the somatic and psychological well-being of the child can be very radical and sometimes irreversible. The earlier a person is affected by thyroid disease, the more the development of personality is affected and the bigger the delay from their potential development level. The child gets behind in its cognitive, emotional and sexual growth, which, by itself, also influences its processing abilities of the endocrine disease.<ref name="ReferenceB"/>
Children with hyperthyroidism tend to have greater [[mood swings]] and disturbances of behavior, as compared with adults. Their [[attention span]] decreases, they are usually hyperactive and distractible, they sleep poorly, and their school performance deteriorates. Because devastating personality and emotional changes often appear in the child or adolescent with Graves' disease, many hyperthyroid children are (similar to many adults) referred to a developmental specialist or child psychiatrist before the presence of hyperthyroidism is suspected.<ref name="ThyroidManager-Ch10-Groot"/>
==Older patients==
In older patients, emotional instability may be less evident, or depression may occur, and the symptoms and signs are manifestly circulatory. In many, the thyroid is not readily palpable.<ref name="ThyroidManager-Ch10-Groot"/> Symptoms such as [[tachycardia|rapid heart rate]], [[Dyspnea|shortness of breath]] on exertion, and [[edema]] may predominate. Older patients also tend to have more weight loss and less of an increase in appetite. Thus [[Anorexia (symptom)|anorexia]] in this group is fairly frequent, as is [[constipation]].<ref name="ThyroidManager-Ch10-Groot"/> Elderly patients may have what is called "apathetic thyrotoxicosis", a state in which they have less and less severe symptoms, except for weakness, [[Depression (mood)|depression]] and [[lethargy]] (making it even more prone to escape diagnosis).{{citation needed|date=August 2020}}
==Graves' disease and work==
Considering the many signs and symptoms, the generally delayed diagnosis, and the possibility of residual complaints after treatment, it is little wonder that a significant number of people with [[Graves' disease]] have difficulty keeping their job. One study found that of 303 patients successfully treated for hyperthyroidism (77% had Graves' disease) 53% dealt with lack of energy. About one-third were unable to resume their customary work, mainly due to persistent mental problems.<ref name="pmid17044727"/><ref>{{Cite journal| doi = 10.1016/S0306-4530(99)00050-5 | title = Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism | author = Fahrenfort JJ, Wilterdink AM, van der Veen EA | journal = Psychoneuroendocrinology| year = 2000 | volume = 25 | issue = 2 | pages = 201–11 | pmid =10674283| last2 = Wilterdink | last3 = Van Der Veen | s2cid = 25205989 }}</ref> In their 1986 study of 26 patients (10 years after successful treatment of hyperthyroidism), Perrild et al. note that four patients had been granted [[disability pension]]s on the basis of intellectual dysfunction.<ref>{{Cite journal| title = Intellectual impairment after hyperthyroidism | author = Perrild H, Hansen JM, Arnung K, Olsen PZ, Danielsen U. | journal = Acta Endocrinologica| year = 1986 | volume = 112 | issue = 2 | pages = 185–91 | pmid = 3739553 | doi=10.1530/acta.0.1120185| last2 = Hansen | last3 = Arnung | last4 = Olsen | last5 = Danielsen }}</ref> Between 2006 and 2008, Ponto et al. surveyed 250 Graves' disease patients. Of these, 36% were written off sick and 5% even had to take [[Retirement#Early retirement|early retirement]]. In the same study, 34% of 400 questioned physicians reported treating patients with fully impaired earning capacity.<ref>{{Cite journal| title = Graves' Disease: Quality Of Life And Occupational Disability | author = Katharina Ponto | journal = Deutsches Ärzteblatt Online| year = 2009 | volume = 106 | issue = 17 | pages = 283–9 | pmid = 19547630 | pmc = 2689575 | doi = 10.3238/arztebl.2009.0283|name-list-style=vanc| display-authors = 1| last2 = Pitz| first2 = S| last3 = Pfeiffer| first3 = N| last4 = Hommel| first4 = G| last5 = Weber| first5 = MM| last6 = Kahaly| first6 = GJ}}</ref>
Patients can and do recover with appropriate therapy while continuing to work, but more rapid and certain progress is made if a period away from the usual occupation can be provided.<ref name="ThyroidManager-Ch11-Groot"/> Two important considerations are adequate rest and attention to nutrition.<ref name="ThyroidManager-Ch11-Groot"/>
==References==
{{reflist}}
[[Category:Symptoms and signs: Endocrinology, nutrition, and metabolism]]
[[Category:Thyroid disease]]
[[Category:Autoimmune diseases]]