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{{Short description|Excessive production of thyroid hormone}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Distinguish|Hyperthyroxinemia|Hypothyroidism}} {{Use dmy dates|date=April 2020}} {{Infobox medical condition | name = Hyperthyroidism | image = Triiodothyronine.svg | caption = [[Triiodothyronine]] (T<sub>3</sub>, pictured) and [[thyroxine]] (T<sub>4</sub>) are both forms of [[thyroid hormone]]. | field = [[Endocrinology]] | synonyms = Overactive thyroid, hyperthyreosis | symptoms = [[Irritability]], [[muscle weakness]], [[insomnia|sleeping problems]], [[tachycardia|fast heartbeat]], [[heat intolerance]], [[diarrhea]], [[goiter|enlargement of the thyroid]], [[weight loss]]<ref name=NIH2012/> | complications = [[Thyroid storm]]<ref name=Clin2014/> | onset = 20–50 years old<ref name=Clin2014/> | duration = | causes = [[Graves' disease]], [[multinodular goiter]], [[toxic adenoma]], [[thyroiditis|inflammation of the thyroid]], eating too much [[iodine]], too much [[synthetic thyroid hormone]]<ref name=NIH2012/><ref name=Clin2014/> | risks = | diagnosis = Based on symptoms and confirmed by [[blood tests]]<ref name=NIH2012/> | differential = | prevention = | treatment = [[Radioiodine therapy]], medications, thyroid surgery<ref name=NIH2012/> | medication = [[Beta blockers]], [[methimazole]]<ref name=NIH2012/> | prognosis = | frequency = 1.2% (US)<ref name=ATA2011/> | deaths = Rare directly, unless [[thyroid storm]] occurs; associated with increased mortality if untreated (1.23 [[hazard ratio|HR]])<ref name="Lillevang-Johansen Abrahamsen Jørgensen Brix 2017 pp. 2301–2309">{{cite journal | last1=Lillevang-Johansen | first1=Mads | last2=Abrahamsen | first2=Bo | last3=Jørgensen | first3=Henrik Løvendahl | last4=Brix | first4=Thomas Heiberg | last5=Hegedüs | first5=Laszlo | title=Excess Mortality in Treated and Untreated Hyperthyroidism Is Related to Cumulative Periods of Low Serum TSH | journal=The Journal of Clinical Endocrinology & Metabolism | publisher=The Endocrine Society | volume=102 | issue=7 | date=2017-03-28 | issn=0021-972X | doi=10.1210/jc.2017-00166 | pages=2301–2309| pmid=28368540 | s2cid=3806882 | doi-access=free }}</ref> }} <!-- Definition and symptoms --> '''Hyperthyroidism''' is a [[endocrine disease]] in which the [[thyroid gland]] produces excessive amounts of [[thyroid hormone]]s.<ref name=ATA2011/> '''Thyrotoxicosis''' is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperthyroidism.<ref name=ATA2011>{{cite journal | vauthors = Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN | title = Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists | journal = Thyroid | volume = 21 | issue = 6 | pages = 593–646 | date = June 2011 | pmid = 21510801 | doi = 10.1089/thy.2010.0417 }}</ref> Some, however, use the terms interchangeably.<ref>{{cite web| vauthors = Schraga ED |title=Hyperthyroidism, Thyroid Storm, and Graves Disease|website=Medscape|url=http://emedicine.medscape.com/article/767130-overview|access-date=20 April 2015|date=30 May 2014|url-status=live|archive-url=https://web.archive.org/web/20150405111836/http://emedicine.medscape.com/article/767130-overview|archive-date=5 April 2015}}</ref> Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a [[tachycardia|fast heartbeat]], [[heat intolerance]], [[diarrhea]], [[goitre|enlargement of the thyroid]], hand [[tremor]], and [[weight loss]].<ref name=NIH2012/> Symptoms are typically less severe in the elderly and during [[pregnancy]].<ref name=NIH2012/> An uncommon but life-threatening complication is [[thyroid storm]] in which an event such as an [[infection]] results in worsening symptoms such as confusion and a [[hyperthermia|high temperature]]; this often results in death.<ref name=Clin2014/> The opposite is [[hypothyroidism]], when the thyroid gland does not make enough thyroid hormone.<ref>{{cite web|author1=NIDDK|title=Hypothyroidism|url=http://www.niddk.nih.gov/health-information/health-topics/endocrine/hypothyroidism/Pages/fact-sheet.aspx|access-date=20 April 2015|date=13 March 2013|url-status=live|archive-url=https://web.archive.org/web/20160305010654/http://www.niddk.nih.gov/health-information/health-topics/endocrine/hypothyroidism/Pages/fact-sheet.aspx|archive-date=5 March 2016}}</ref> <!-- Cause and diagnosis --> [[Graves' disease]] is the cause of about 50% to 80% of the cases of hyperthyroidism in the United States.<ref name=NIH2012>{{Cite web|title = Hyperthyroidism|url = http://www.niddk.nih.gov/health-information/health-topics/endocrine/hyperthyroidism/Pages/fact-sheet.aspx|website = www.niddk.nih.gov|access-date = 2015-04-02|date = July 2012|url-status = dead|archive-url = https://web.archive.org/web/20150404183926/http://www.niddk.nih.gov/health-information/health-topics/endocrine/hyperthyroidism/Pages/fact-sheet.aspx|archive-date = 4 April 2015}}</ref><ref name=NEJM2008>{{cite journal | vauthors = Brent GA | title = Clinical practice. Graves' disease | journal = The New England Journal of Medicine | volume = 358 | issue = 24 | pages = 2594–2605 | date = June 2008 | pmid = 18550875 | doi = 10.1056/NEJMcp0801880 }}</ref> Other causes include [[multinodular goiter]], [[toxic adenoma]], [[thyroiditis|inflammation of the thyroid]], eating too much [[iodine]], and too much [[synthetic thyroid hormone]].<ref name=NIH2012/><ref name=Clin2014>{{cite journal | vauthors = Devereaux D, Tewelde SZ | title = Hyperthyroidism and thyrotoxicosis | journal = Emergency Medicine Clinics of North America | volume = 32 | issue = 2 | pages = 277–292 | date = May 2014 | pmid = 24766932 | doi = 10.1016/j.emc.2013.12.001 }}</ref> A less common cause is a [[pituitary adenoma]].<ref name=NIH2012/> The diagnosis may be suspected based on signs and symptoms and then confirmed with blood tests.<ref name=NIH2012/> Typically blood tests show a low [[thyroid stimulating hormone]] (TSH) and raised [[triiodothyronine|T<sub>3</sub>]] or [[thyroxine|T<sub>4</sub>]].<ref name=NIH2012/> [[Radioiodine]] uptake by the thyroid, [[thyroid scan]], and measurement of [[antithyroid autoantibodies]] (thyroidal thyrotropin receptor antibodies are positive in Graves disease) may help determine the cause.<ref name=NIH2012/> <!-- Management and epidemiology --> Treatment depends partly on the cause and severity of disease.<ref name=NIH2012/> There are three main treatment options: [[radioiodine therapy]], medications, and thyroid surgery.<ref name=NIH2012/> Radioiodine therapy involves taking [[iodine-131]] by mouth which is then concentrated in and destroys the thyroid over weeks to months.<ref name=NIH2012/> The resulting hypothyroidism is treated with synthetic thyroid hormone.<ref name=NIH2012/> Medications such as [[beta blockers]] may control the symptoms, and [[anti-thyroid medication]]s such as [[methimazole]] may temporarily help people while other treatments are having an effect.<ref name=NIH2012/> Surgery to remove the thyroid is another option.<ref name=NIH2012/> This may be used in those with very large thyroids or when cancer is a concern.<ref name=NIH2012/> In the United States hyperthyroidism affects about 1.2% of the population.<ref name=ATA2011/> Worldwide, hyperthyroidism affects 2.5% of adults.<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=1472–1483 |doi=10.1001/jama.2023.19052|pmid=37847271 |pmc=10873132 |s2cid=265937262 }}</ref> It occurs between two and ten times more often in women.<ref name=NIH2012/> Onset is commonly between 20 and 50 years of age.<ref name=Clin2014/> Overall the disease is more common in those over the age of 60 years.<ref name=NIH2012/> ==Signs and symptoms== Hyperthyroidism may be asymptomatic or present with significant symptoms.<ref name=Clin2014/> Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, [[insomnia|trouble sleeping]], thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.<ref>{{cite journal | vauthors = Koutras DA | title = Disturbances of menstruation in thyroid disease | journal = Annals of the New York Academy of Sciences | volume = 816 | issue = 1 Adolescent Gy | pages = 280–284 | date = June 1997 | pmid = 9238278 | doi = 10.1111/j.1749-6632.1997.tb52152.x | s2cid = 5840966 | bibcode = 1997NYASA.816..280K }}</ref><ref>{{cite book | vauthors = Shahid MA, Ashraf MA, Sharma S | chapter = Physiology, Thyroid Hormone | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing| date = January 2021 | pmid = 29763182 }}</ref> [[File:Proptosis and lid retraction from Graves' Disease.jpg|left|thumb|[[Exophthalmos]] seen in [[Graves' ophthalmopathy|Graves’ ophthalmopathy]]]] Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates [[metabolism]] and disrupts the normal functioning of [[sympathetic nervous system]], causing "speeding up" of various body systems and symptoms resembling an overdose of [[epinephrine]] (adrenaline). These include fast heartbeat and symptoms of [[palpitation]]s, nervous system [[tremor]] such as of the hands and [[anxiety (mood)|anxiety]] symptoms, digestive system [[hypermotility]], unintended weight loss, and, in [[lipid panel]] blood tests, a lower and sometimes unusually low serum [[cholesterol]].<ref name="Thyrotoxicosis and Hyperthyroidism">{{cite web |url= https://www.lecturio.com/concepts/thyrotoxicosis-and-hyperthyroidism/| title= Thyrotoxicosis and Hyperthyroidism |website=The Lecturio Medical Concept Library |access-date= 7 August 2021}}</ref> Major clinical signs of hyperthyroidism include [[weight loss]] (often accompanied by an increased [[appetite]]), anxiety, [[heat intolerance]], hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability, [[hyperglycemia|high blood sugar]],<ref name="Thyrotoxicosis and Hyperthyroidism"/> [[polyuria|excessive urination]], [[polydipsia|excessive thirst]], [[delirium]], [[tremor]], [[pretibial myxedema]] (in [[Graves' disease]]), [[emotional lability]], and sweating. [[Panic attacks]], inability to concentrate, and [[memory]] problems may also occur. [[Psychosis]] and [[paranoia]], common during [[thyroid storm]], are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after a [[euthyroid]] state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence of [[affective]] and cognitive symptoms for several months to up to 10 years after a euthyroid state is established.<ref>{{cite book|title=Bradley's neurology in clinical practice.|publisher=Elsevier/Saunders|location=Philadelphia, PA|chapter=Depression and Psychosis in Neurological Practice.|year=2012|isbn=978-1-4377-0434-1|pages=102–103|edition=6th}}</ref> In addition, those with hyperthyroidism may present with a variety of physical symptoms such as [[palpitations]] and [[Heart arrhythmia|abnormal heart rhythms]] (the notable ones being [[atrial fibrillation]]), shortness of breath ([[dyspnea]]), loss of [[libido]], [[amenorrhea]], [[nausea]], [[vomiting]], [[diarrhea]], [[gynecomastia]] and [[feminization (biology)|feminization]].<ref>{{cite journal | vauthors = Chan WB, Yeung VT, Chow CC, So WY, Cockram CS | title = Gynaecomastia as a presenting feature of thyrotoxicosis | journal = Postgraduate Medical Journal | volume = 75 | issue = 882 | pages = 229–231 | date = April 1999 | pmid = 10715765 | pmc = 1741202 | doi = 10.1136/pgmj.75.882.229 }}</ref> Long term untreated hyperthyroidism can lead to [[osteoporosis]]. These classical symptoms may not be present often in the elderly.<ref>{{Cite web |title=Hyperthyroidism - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/hyperthyroidism/symptoms-causes/syc-20373659 |access-date=2024-06-28 |website=Mayo Clinic |language=en}}</ref> Bone loss, which is associated with overt but not subclinical hyperthyroidism, may occur in 10 to 20% of patients. This may be due to an increase in bone remodelling and a decrease in bone density, and increases fracture risk. It is more common in postmenopausal women; less so in younger women, and men. Bone disease related to hyperthyroidism was first described by Frederick von Recklinghausen, in 1891; he described the bones of a woman who died of hyperthyroidism as appearing "worm-eaten".<ref>{{cite web | last=Miragaya | first=Joanna | title=Preventing 'Worm-eaten Bones' From Hyperthyroidism | website=Medscape | date=31 July 2023 | url=https://www.medscape.com/viewarticle/994801}}</ref> Neurological manifestations can include [[tremor]]s, [[Chorea (disease)|chorea]], [[myopathy]], and in some susceptible individuals (in particular of Asian descent) [[Thyrotoxic periodic paralysis|periodic paralysis]]. An association between thyroid disease and [[myasthenia gravis]] has been recognized. Thyroid disease, in this condition, is [[autoimmune]] in nature and approximately 5% of people with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is becoming better understood over the past 15 years.<ref name="pmid16840920">{{cite journal | vauthors = Trabelsi L, Charfi N, Triki C, Mnif M, Rekik N, Mhiri C, Abid M | title = [Myasthenia gravis and hyperthyroidism: two cases] | language = French | journal = Annales d'Endocrinologie | volume = 67 | issue = 3 | pages = 265–9 | date = June 2006 | pmid = 16840920 | doi = 10.1016/s0003-4266(06)72597-5 }}</ref><ref>{{cite journal |first1=Rong-hua |last1=Song |first2=Qiu-ming |last2=Yao |first3=Bin |last3=Wang |first4=Qian |last4=Li |first5=Xi |last5=Jia |first6=Jin-an |last6=Zhang |title=Thyroid disorders in patients with myasthenia gravis: A systematic review and meta-analysis |journal=Autoimmunity Reviews |issue=10 |date=October 2019 |volume=18 |doi=10.1016/j.autrev.2019.102368 |pmid=31404702 |s2cid=199549144 |url=https://doi.org/10.1016/j.autrev.2019.102368 |access-date=2024-01-22|url-access=subscription }}</ref><ref>{{cite journal |vauthors=Zhu Y, Wang B, Hao Y, Zhu R |title=Clinical features of myasthenia gravis with neurological and systemic autoimmune diseases |journal=Front Immunol |date=September 2023 |volume=14 |issue=14:1223322 |doi=10.3389/fimmu.2023.1223322 |doi-access=free |pmid=37781409 |pmc= 10538566}} </ref>[[File:Blausen 0534 Goiter.png|thumb|Illustration depicting enlarged thyroid that may be associated with hyperthyroidism|255x255px]]In [[Graves' disease]], [[ophthalmopathy]] may cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).<ref name="next.thyroid.org">{{cite web |url=http://next.thyroid.org/patients/patient_brochures/hyperthyroidism.html |title=Hyperthyroidism | publisher = American Thyroid Association |access-date=2010-05-10 |url-status=dead |archive-url=https://web.archive.org/web/20110305123450/http://next.thyroid.org/patients/patient_brochures/hyperthyroidism.html |archive-date=5 March 2011}}</ref> Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), [[extraocular muscles|extraocular muscle]] weakness, and [[Lid lag|lid-lag]].<ref>{{Cite book| vauthors = Mehtap C |url=http://worldcat.org/oclc/472720688|title=Differential diagnosis of hyperthyroidism|publisher=Nova Science Publishers|year=2010|isbn=978-1-61668-242-2|pages=xii|oclc=472720688}}</ref> In hyperthyroid ''stare'' ([[Dalrymple sign]]) the eyelids are retracted upward more than normal (the normal position is at the superior [[Corneal limbus|corneoscleral limbus]], where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag ([[von Graefe's sign]]), when the person tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.{{Citation needed|date=December 2010}} Neither of these ocular signs should be confused with [[exophthalmos]] (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves' disease (note that not all exophthalmos is caused by Graves' disease, but when present with hyperthyroidism is diagnostic of Graves' disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.<ref>{{cite web|author=Faculty of Medicine & Dentistry |title=Course-Based Physical Examination – Endocrinology – Endocrinology Objectives (Thyroid Exam) |url=http://www.med.ualberta.ca/education/ugme/clinicaled12/clinskills_endocrinology.cfm?yr=1 |work=Undergraduate Medical Education |year=2006 |publisher=University of Alberta |access-date=28 January 2007 |url-status=dead |archive-url=https://web.archive.org/web/20080119214105/http://www.med.ualberta.ca/education/ugme/clinicaled12/clinskills_endocrinology.cfm?yr=1 |archive-date=19 January 2008}}</ref> ===Thyroid storm=== {{main|Thyroid storm}} Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and often [[cardiac arrhythmia|irregular heart beat]], high temperature, vomiting, diarrhea, and mental agitation. Symptoms may not be typical in the young, old, or pregnant.<ref name=Clin2014/> It usually occurs due to untreated hyperthyroidism and can be provoked by infections.<ref name=Clin2014/> It is a [[medical emergency]] and requires hospital care to control the symptoms rapidly. The mortality rate in thyroid storm is 3.6-17%, usually due to multi-organ system failure.<ref name="Lee 2023" /> ===Hypothyroidism=== Hyperthyroidism due to certain types of [[Hashimoto's thyroiditis|thyroiditis]] can eventually lead to [[hypothyroidism]] (a ''lack'' of thyroid hormone), as the thyroid gland is damaged. Also, [[radioiodine]] treatment of Graves' disease often eventually leads to hypothyroidism. Such hypothyroidism may be diagnosed with thyroid hormone testing and treated by oral thyroid hormone supplementation.<ref>{{Cite web|title=Hypothyroidism - Diagnosis and treatment - Mayo Clinic|url=https://www.mayoclinic.org/diseases-conditions/hypothyroidism/diagnosis-treatment/drc-20350289|access-date=2021-05-06|website=www.mayoclinic.org}}</ref> ==Causes== [[File:Causes of hyperthyroidism.png|thumb|Most common causes of hyperthyroidism by age.<ref>{{cite journal | vauthors = Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Laurberg P | title = Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study | journal = European Journal of Endocrinology | volume = 164 | issue = 5 | pages = 801–809 | date = May 2011 | pmid = 21357288 | doi = 10.1530/EJE-10-1155 | s2cid = 25049060 | doi-access = free }}</ref>]] There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism.<ref>{{cite web |url=http://www.endocrineweb.com/hyper2.html |title=Hyperthyroidism Overview |access-date=2010-04-27 |url-status=live |archive-url=https://web.archive.org/web/20100428091701/http://www.endocrineweb.com/hyper2.html |archive-date=28 April 2010}}</ref> Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions. The major causes in humans are: * [[Graves' disease]]. An autoimmune disease (usually, the most common cause with 50–80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet.<ref name="AnderssonZimmermann2010">{{cite book | vauthors = Andersson M, Zimmermann MB |title=Thyroid Function Testing |chapter=Influence of Iodine Deficiency and Excess on Thyroid Function Tests |volume=28 |year=2010 |pages=45–69 |issn=1566-0729 |doi=10.1007/978-1-4419-1485-9_3 |series=Endocrine Updates |isbn=978-1-4419-1484-2 }}</ref> It is eight times more common in females than males and often occurs in young females, around 20 to 40 years of age.<ref>{{Cite web |last=Services |first=Department of Health & Human |title=Thyroid - hyperthyroidism |url=https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/thyroid-hyperthyroidism |access-date=2025-05-23 |website=www.betterhealth.vic.gov.au |language=en}}</ref> * [[Toxic thyroid adenoma]] (the most common cause in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)<ref name="AnderssonZimmermann2010" /> * [[Toxic multinodular goiter]]{{cn|date=July 2024}} High blood levels of thyroid hormones (most accurately termed [[hyperthyroxinemia]]) can occur for a number of other reasons: * [[Inflammation]] of the thyroid is called [[thyroiditis]]. There are several different kinds of thyroiditis including [[Hashimoto's thyroiditis]] (Hypothyroidism immune-mediated), and [[subacute thyroiditis]] (de Quervain's). These may be ''initially'' associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism. * Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of eating ground beef or pork contaminated with thyroid tissue, and thus thyroid hormones (termed ''hamburger thyrotoxicosis'' or ''alimentary thyrotoxicosis'').<ref>{{cite journal | vauthors = Parmar MS, Sturge C | title = Recurrent hamburger thyrotoxicosis | journal = CMAJ | volume = 169 | issue = 5 | pages = 415–417 | date = September 2003 | pmid = 12952802 | pmc = 183292 }}</ref> Pharmacy compounding errors may also be a cause.<ref name="pmid25762821">{{cite journal | vauthors = Bains A, Brosseau AJ, Harrison D | title = Iatrogenic thyrotoxicosis secondary to compounded liothyronine | journal = The Canadian Journal of Hospital Pharmacy | volume = 68 | issue = 1 | pages = 57–9 | date = 2015 | pmid = 25762821 | pmc = 4350501 | doi = 10.4212/cjhp.v68i1.1426 }}</ref> * [[Amiodarone]], an [[antiarrhythmic agent|antiarrhythmic drug]], is structurally similar to thyroxine and may cause either under-or [[Amiodarone induced thyrotoxicosis|overactivity]] of the thyroid.{{cn|date=July 2024}} * [[Postpartum thyroiditis]] (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment. * A [[struma ovarii]] is a rare form of monodermal [[teratoma]] that contains mostly thyroid tissue, which leads to hyperthyroidism. * Excess iodine consumption notably from algae such as [[kelp]]. Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as [[levothyroxine]] (a phenomenon known as exogenous thyrotoxicosis, [[Human gastrointestinal tract|alimentary]] thyrotoxicosis, or [[Occult (disambiguation)|occult]] factitial thyrotoxicosis).<ref name="emedicine.medscape">{{cite web | vauthors = Floyd JL | orig-date = 2009 | title = Thyrotoxicosis | work = eMedicine |url=http://emedicine.medscape.com/article/383062-overview |url-status=live |archive-url=https://web.archive.org/web/20100317115206/http://emedicine.medscape.com/article/383062-overview |archive-date=17 March 2010|date=2017-03-21 }}</ref> Hypersecretion of [[thyroid stimulating hormone]] (TSH), which in turn is almost always caused by a [[pituitary adenoma]], accounts for much less than 1 percent of hyperthyroidism cases.<ref>{{cite web | url = http://www.uptodate.com/contents/thyrotropin-tsh-secreting-pituitary-adenomas | title = Thyrotropin (TSH)-secreting pituitary adenomas. | work = UpToDate | archive-url = https://web.archive.org/web/20110218143345/http://www.uptodate.com/contents/thyrotropin-tsh-secreting-pituitary-adenomas | archive-date=18 February 2011 | vauthors = Weiss RE, Refetoff S | quote = Last literature review version 19.1: January 2011. This topic last updated: 2 July 2009 }}</ref> ==Diagnosis== Measuring the level of [[thyroid-stimulating hormone]] (TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamus's TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T<sub>4</sub> and/or T<sub>3</sub> in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness ([[euthyroid sick syndrome]]) and so checking the T<sub>4</sub> and T<sub>3</sub> is still clinically useful.<ref name="Thyrotoxicosis and Hyperthyroidism"/> Measuring specific [[antibody|antibodies]], such as anti-TSH-receptor antibodies in Graves' disease, or anti-thyroid peroxidase in [[Hashimoto's thyroiditis]]—a common cause of [[hypothyroidism]]—may also contribute to the diagnosis. The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T<sub>4</sub> and T<sub>3</sub> levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb much more iodine than healthy persons which includes radioactive iodine which is easy to measure. A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland.<ref name="Thyrotoxicosis and Hyperthyroidism"/> Thyroid [[scintigraphy]] is a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: an [[Radioactive iodine uptake test|iodine uptake test]] and a scan (imaging) with a [[gamma camera]]. The uptake test involves administering a dose of radioactive iodine (radioiodine), traditionally [[iodine-131]] (<sup>131</sup>I), and more recently [[iodine-123]] (<sup>123</sup>I). [[Iodine-123]] may be the preferred radionuclide in some clinics due to its more favorable radiation [[dosimetry]] (i.e. less radiation dose to the person per unit administered radioactivity) and a gamma photon energy more amenable to imaging with the [[gamma camera]]. For the imaging scan, I-123 is considered an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis.<ref>{{cite journal | vauthors = Park HM | title = 123I: almost a designer radioiodine for thyroid scanning | journal = Journal of Nuclear Medicine | volume = 43 | issue = 1 | pages = 77–78 | date = January 2002 | pmid = 11801707 | url = http://jnm.snmjournals.org/cgi/content/full/43/1/77 | access-date = 2010-05-10 | url-status = dead | archive-url = https://web.archive.org/web/20081012074621/http://jnm.snmjournals.org/cgi/content/full/43/1/77 | archive-date = 12 October 2008 }}</ref> Thyroid scintigraphy should not be performed in those who are pregnant, a thyroid ultrasound with color flow doppler may be obtained as an alternative in these circumstances.<ref name="Lee 2023" /> Typical administration involves a pill or liquid containing sodium iodide (NaI) taken orally, which contains a small amount of [[iodine-131]], amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used in [[X-ray computed tomography|CT scan]], [[intravenous pyelogram]] (IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some people with hyperthyroidism may experience a slight allergic reaction to the diagnostic radioiodine and may be given an [[antihistamine]].{{citation needed|date=August 2020}} The person returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4 minutes while the uptake % (''i.e.,'' percentage) is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with a [[gamma camera]]; a [[radiologist]] will read and prepare a report indicating the uptake % and comments after examining the images. People with hyperthyroid will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10 to 30%. In addition to testing the TSH levels, many doctors test for T<sub>3</sub>, Free T<sub>3</sub>, T<sub>4</sub>, and/or Free T<sub>4</sub> for more detailed results. Free T<sub>4</sub> is unbound to any protein in the blood. Adult limits for these hormones are: TSH (units): 0.45 – 4.50 uIU/mL; T<sub>4</sub> Free/Direct (nanograms): 0.82 – 1.77 ng/dl; and T<sub>3</sub> (nanograms): 71 – 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T<sub>4</sub> and/or T<sub>3</sub>. See a complete table of normal range limits for thyroid function at the [[thyroid gland]] article. In hyperthyroidism CK-MB ([[Creatine kinase]]) is usually elevated.<ref>{{cite book | vauthors = Mesko D, Pullmann R | chapter = Blood - Plasma - Serum | veditors = Marks V, Cantor T, Mesko D, Pullmann R, Nosalova G | title = Differential diagnosis by laboratory medicine: a quick reference for physicians. | publisher = Springer Science & Business Media | date = December 2012 | page = 156 | isbn = 978-3-642-55600-5 }}</ref> <gallery> File:Hyperthyroidism (1).jpg File:Hyperthyroidism (2).jpg File:Hyperthyroidism (3).jpg </gallery> ===Subclinical=== {{See also|Symptoms and signs of Graves' disease#Subclinical hyperthyroidism}} In overt primary hyperthyroidism, TSH levels are low and T<sub>4</sub> and T<sub>3</sub> levels are high. Subclinical hyperthyroidism is a milder form of hyperthyroidism characterized by low or undetectable serum TSH level, but with a normal serum free thyroxine level.<ref>{{cite journal | vauthors = Biondi B, Cooper DS | title = The clinical significance of subclinical thyroid dysfunction | journal = Endocrine Reviews | volume = 29 | issue = 1 | pages = 76–131 | date = February 2008 | pmid = 17991805 | doi = 10.1210/er.2006-0043 | doi-access = free }}</ref> Although the evidence for doing so is not definitive, treatment of elderly persons having subclinical hyperthyroidism could reduce the number of cases of [[atrial fibrillation]].<ref>{{cite journal | vauthors = Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ | title = Subclinical thyroid disease: scientific review and guidelines for diagnosis and management | journal = JAMA | volume = 291 | issue = 2 | pages = 228–238 | date = January 2004 | pmid = 14722150 | doi = 10.1001/jama.291.2.228 }}</ref> There is also an increased risk of [[bone fracture]]s (by 42%) in people with subclinical hyperthyroidism; there is insufficient evidence to say whether treatment with antithyroid medications would reduce that risk.<ref>{{cite journal | vauthors = Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, da Costa BR, Wirth CD, Peeters RP, Åsvold BO, den Elzen WP, Luben RN, Imaizumi M, Bremner AP, Gogakos A, Eastell R, Kearney PM, Strotmeyer ES, Wallace ER, Hoff M, Ceresini G, Rivadeneira F, Uitterlinden AG, Stott DJ, Westendorp RG, Khaw KT, Langhammer A, Ferrucci L, Gussekloo J, Williams GR, Walsh JP, Jüni P, Aujesky D, Rodondi N | title = Subclinical thyroid dysfunction and fracture risk: a meta-analysis | journal = JAMA | volume = 313 | issue = 20 | pages = 2055–2065 | date = May 2015 | pmid = 26010634 | pmc = 4729304 | doi = 10.1001/jama.2015.5161 }}</ref> A 2022 meta-analysis found subclinical hyperthyroidism to be associated with cardiovascular death.<ref>{{cite journal |last1=Müller |first1=P |last2=Leow |first2=MK |last3=Dietrich |first3=JW |title=Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence. |journal=Frontiers in Cardiovascular Medicine |date=2022 |volume=9 |pages=942971 |doi=10.3389/fcvm.2022.942971 |pmid=36046184|pmc=9420854 |doi-access=free }}</ref> ===Screening=== In those without symptoms who are not pregnant there is little evidence for or against screening.<ref>{{cite journal | vauthors = LeFevre ML | title = Screening for thyroid dysfunction: U.S. Preventive Services Task Force recommendation statement | journal = Annals of Internal Medicine | volume = 162 | issue = 9 | pages = 641–650 | date = May 2015 | pmid = 25798805 | doi = 10.7326/m15-0483 | s2cid = 207538375 }}</ref> == Treatment == ===Antithyroid drugs=== Thyrostatics ([[Antithyroid agent|antithyroid drugs]]) are drugs that inhibit the production of thyroid hormones, such as [[carbimazole]] (used in the UK) and [[methimazole]] (used in the US, Germany and Russia), and [[propylthiouracil]]. Thyrostatics are believed to work by inhibiting the [[iodination]] of [[thyroglobulin]] by [[thyroperoxidase]] and, thus, the formation of tetraiodothyronine (T<sub>4</sub>). Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T<sub>4</sub> to the active form T<sub>3</sub>. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.<ref name="Thyrotoxicosis and Hyperthyroidism"/> ===Beta-blockers=== Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta-adrenergic receptors on cell surfaces. [[Beta blockers]], typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a person with hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition.<ref>{{Cite web|title=UpToDate|url=https://www.uptodate.com/contents/beta-blockers-in-the-treatment-of-hyperthyroidism|access-date=2021-05-17|website=www.uptodate.com}}</ref> Some minimal effect on thyroid hormone production however also comes with [[propranolol]]—which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and [[heat intolerance]]. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T<sub>4</sub> to T<sub>3</sub>, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism.<ref>{{cite journal | vauthors = Eber O, Buchinger W, Lindner W, Lind P, Rath M, Klima G, Langsteger W, Költringer P | title = The effect of D- versus L-propranolol in the treatment of hyperthyroidism | journal = Clinical Endocrinology | volume = 32 | issue = 3 | pages = 363–372 | date = March 1990 | pmid = 2344697 | doi = 10.1111/j.1365-2265.1990.tb00877.x | s2cid = 37948268 }}</ref> [[Propranolol]] in the UK, and [[metoprolol]] in the US, are most frequently used to augment treatment for people with hyperthyroid .<ref name=pmid1352658>{{cite journal | vauthors = Geffner DL, Hershman JM | title = Beta-adrenergic blockade for the treatment of hyperthyroidism | journal = The American Journal of Medicine | volume = 93 | issue = 1 | pages = 61–68 | date = July 1992 | pmid = 1352658 | doi = 10.1016/0002-9343(92)90681-Z }}</ref> ===Diet=== People with autoimmune hyperthyroidism (such as in [[Graves' disease|Grave's disease]]) should not eat foods high in iodine, such as [[edible seaweed]] and [[seafood]].<ref name=NIH2012/> From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children.<ref name=BI72213>{{cite news|title=How Adding Iodine To Salt Resulted in a Decade's Worth of IQ Gains for the United States|url=http://www.businessinsider.com/iodization-effect-on-iq-2013-7|access-date=23 July 2013|newspaper=Business Insider|date=22 July 2013| vauthors = Nisen M |url-status=live|archive-url=https://web.archive.org/web/20130723154256/http://www.businessinsider.com/iodization-effect-on-iq-2013-7|archive-date=23 July 2013}}</ref> ===Surgery=== [[Surgery]] ([[thyroidectomy]] to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the [[parathyroid glands]], and of cutting the [[recurrent laryngeal nerve]], making swallowing difficult, and even simply generalized [[staphylococcus|staphylococcal]] infection as with any major surgery. Some people with Graves' may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.<ref>{{cite journal | vauthors = Catania A, Guaitoli E, Carbotta G, Bianchini M, Di Matteo FM, Carbotta S, Nardi M, Fabiani E, Grani G, D'Andrea V, Fumarola A | title = Total thyroidectomy for Graves' disease treatment | journal = La Clinica Terapeutica | volume = 164 | issue = 3 | pages = 193–196 | date = 2012 | pmid = 23868618 | doi = 10.7417/CT.2013.1548 }}</ref> A 2019 [[systematic review]] concluded that the available evidence shows no difference between visually identifying the nerve or utilizing intraoperative [[neuroimaging]] during surgery, when trying to prevent injury to recurrent laryngeal nerve during thyroid surgery.<ref>{{Cite journal |last1=Cirocchi |first1=Roberto |last2=Arezzo |first2=Alberto |last3=D'Andrea |first3=Vito |last4=Abraha |first4=Iosief |last5=Popivanov |first5=Georgi I |last6=Avenia |first6=Nicola |last7=Gerardi |first7=Chiara |last8=Henry |first8=Brandon Michael |last9=Randolph |first9=Justus |last10=Barczyñski |first10=Marcin |date=2019-01-19 |editor-last=Cochrane Metabolic and Endocrine Disorders Group |title=Intraoperative neuromonitoring versus visual nerve identification for prevention of recurrent laryngeal nerve injury in adults undergoing thyroid surgery |journal=Cochrane Database of Systematic Reviews |volume=1 |issue=1 |pages=CD012483 |language=en |doi=10.1002/14651858.CD012483.pub2|pmid=30659577 |pmc=6353246 }}</ref> If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.<ref>{{cite book |title=Endocrinology : adult and pediatric|date=2010|publisher=Saunders/Elsevier|location=Philadelphia|isbn=978-1-4160-5583-9|page=Chapter 82|edition=6th|url=https://www.inkling.com/read/endocrinology-jameson-de-groot-6th/chapter-82/chapter082-reader-1 |url-access=subscription}}</ref> ===Radioiodine=== In [[iodine-131]] ([[radioiodine]]) [[Radiation therapy#Radioisotope and therapy (RIT)|radioisotope therapy]], which was first pioneered by Dr. [[Saul Hertz]],<ref name="Vignette">{{cite journal | vauthors = Hertz BE, Schuller KE | title = Saul Hertz, MD (1905-1950): a pioneer in the use of radioactive iodine | journal = Endocrine Practice | volume = 16 | issue = 4 | pages = 713–5 | date = 2010 | pmid = 20350908 | doi = 10.4158/EP10065.CO }}</ref> radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually [[iodine-123]] or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. People not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.<ref name="Pmid">{{cite journal | vauthors = Metso S, Auvinen A, Huhtala H, Salmi J, Oksala H, Jaatinen P | title = Increased cancer incidence after radioiodine treatment for hyperthyroidism | journal = Cancer | volume = 109 | issue = 10 | pages = 1972–1979 | date = May 2007 | pmid = 17393376 | doi = 10.1002/cncr.22635 | s2cid = 19734123 | doi-access = free }}</ref> Since iodine is picked up more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breastfeeding ([[Breast|breast tissue]] also picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy ([[levothyroxine]]) taken orally each day replaces the thyroid hormone that is normally produced by the body.<ref>{{cite web | work = AHFS Patient Medication Information | publisher = American Society of Health-System Pharmacists, Inc | title = levothyroxine | url = https://medlineplus.gov/druginfo/meds/a682461.html | access-date = 25 October 2021 }}</ref> There is extensive experience, over many years, of the use of radioiodine in the treatment of thyroid overactivity and this experience does not indicate any increased risk of thyroid cancer following treatment. However, a study from 2007 has reported an increased number of cancer cases after radioiodine treatment for hyperthyroidism.<ref name="Pmid" /> The principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Graves' vs. toxic goiter, vs. hot nodule etc.), the success rate in achieving definitive resolution of the hyperthyroidism may vary from 75 to 100%. A major expected side-effect of radioiodine in people with Graves' disease is the development of lifelong [[hypothyroidism]], requiring daily treatment with thyroid hormone. On occasion, some people may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered.<ref>{{cite web |url=http://www.mythyroid.com/iodinehyper.html |title=Radioactive Iodine | date = 2005 | work = MyThyroid.com |access-date=2010-05-11 |url-status=dead |archive-url=https://web.archive.org/web/20100305000205/http://www.mythyroid.com/iodinehyper.html |archive-date=5 March 2010 }}</ref> People with Graves' disease manifesting moderate or severe [[Graves' ophthalmopathy]] are cautioned against radioactive iodine-131 treatment, since it has been shown to exacerbate existing thyroid eye disease. People with mild or no ophthalmic symptoms can mitigate their risk with a concurrent six-week course of [[prednisone]]. The mechanisms proposed for this side effect involve a TSH receptor common to both [[thyroid epithelial cell|thyrocytes]] and retro-orbital tissue.<ref>{{cite journal | vauthors = Walsh JP, Dayan CM, Potts MJ | title = Radioiodine and thyroid eye disease | journal = BMJ | volume = 319 | issue = 7202 | pages = 68–69 | date = July 1999 | pmid = 10398607 | pmc = 1116221 | doi = 10.1136/bmj.319.7202.68 }}</ref> As radioactive iodine treatment results in the destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormones being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some people, treatment with medications such as [[beta blocker]]s ([[propranolol]], [[atenolol]], etc.) may be useful during this period of time. Most people do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc.{{citation needed|date=August 2020}} It is recommended that breastfeeding be stopped at least six weeks before radioactive iodine treatment and that it not be resumed, although it can be done in future pregnancies. It also shouldn't be done during pregnancy, and pregnancy should be put off until at least 6–12 months after treatment.<ref>{{Cite web |title=Radioactive Iodine Therapy: What is it, Treatment, Side Effects |url=https://my.clevelandclinic.org/health/treatments/16477-radioiodine-radioactive-iodine-therapy |access-date=2022-04-20 |website=Cleveland Clinic}}</ref><ref>{{Cite web |title=Radioactive Iodine |url=https://www.thyroid.org/radioactive-iodine/ |access-date=2022-04-20 |website=American Thyroid Association |language=en-US}}</ref> A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves' thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma.<ref name=pmid1710255>{{cite journal | vauthors = Berglund J, Christensen SB, Dymling JF, Hallengren B | title = The incidence of recurrence and hypothyroidism following treatment with antithyroid drugs, surgery or radioiodine in all patients with thyrotoxicosis in Malmö during the period 1970-1974 | journal = Journal of Internal Medicine | volume = 229 | issue = 5 | pages = 435–442 | date = May 1991 | pmid = 1710255 | doi = 10.1111/j.1365-2796.1991.tb00371.x | s2cid = 10510932 }}</ref> Use of higher doses of radioiodine reduces the number of cases of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life.<ref name=pmid16390021>{{cite journal | vauthors = Esfahani AF, Kakhki VR, Fallahi B, Eftekhari M, Beiki D, Saghari M, Takavar A | title = Comparative evaluation of two fixed doses of 185 and 370 MBq 131I, for the treatment of Graves' disease resistant to antithyroid drugs | journal = Hellenic Journal of Nuclear Medicine | volume = 8 | issue = 3 | pages = 158–161 | year = 2005 | pmid = 16390021 }}</ref> There is increased sensitivity to radioiodine therapy in thyroids appearing on [[Medical ultrasonography|ultrasound scans]] as more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic).<ref name=pmid17609305>{{cite journal | vauthors = Markovic V, Eterovic D | title = Thyroid echogenicity predicts outcome of radioiodine therapy in patients with Graves' disease | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 9 | pages = 3547–3552 | date = September 2007 | pmid = 17609305 | doi = 10.1210/jc.2007-0879 | doi-access = free }}</ref> ===Thyroid storm=== [[Thyroid storm]] presents with extreme symptoms of hyperthyroidism. It is treated aggressively with [[resuscitation]] measures along with a combination of the above modalities including: intravenous beta blockers such as [[propranolol]], followed by a [[thioamide]] such as [[methimazole]], an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous [[steroid]] such as [[hydrocortisone]].<ref>{{cite book |title=Emergency Medicine: A Comprehensive Study Guide | edition = Sixth | vauthors = Tintinalli J |year=2004 |publisher=McGraw-Hill Professional |isbn=978-0-07-138875-7 |page=1312 }}</ref> [[Propylthiouracil]] is the preferred thioamide in thyroid storm as it can prevent the conversion of T4 to the more active T3 in the peripheral tissues in addition to inhibiting thyroid hormone production.<ref name="Lee 2023" /> === Alternative medicine === In countries such as China, herbs used alone or with antithyroid medications are used to treat hyperthyroidism.<ref name=":0">{{cite journal | vauthors = Zen XX, Yuan Y, Liu Y, Wu TX, Han S | title = Chinese herbal medicines for hyperthyroidism | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD005450 | date = April 2007 | volume = 2007 | pmid = 17443591 | pmc = 6544778 | doi = 10.1002/14651858.CD005450.pub2 }}</ref> Very low quality evidence suggests that [[Chinese herbology|traditional Chinese herbal medications]] may be beneficial when taken along with routine hyperthyroid medications, however, there is no reliable evidence to determine the effectiveness of Chinese herbal medications for treating hyperthyroidism.<ref name=":0" /> ==Epidemiology== In the United States hyperthyroidism affects about 1.2% of the population.<ref name=ATA2011/> About half of these cases have obvious symptoms while the other half do not.<ref name=Clin2014/> It occurs between two and ten times more often in women.<ref name=NIH2012/> The disease is more common in those over the age of 60 years.<ref name=NIH2012/> [[Signs and symptoms of Graves' disease#Sub-clinical hyperthyroidism|Subclinical hyperthyroidism]] modestly increases the risk of cognitive impairment and dementia.<ref>{{cite journal | vauthors = Rieben C, Segna D, da Costa BR, Collet TH, Chaker L, Aubert CE, Baumgartner C, Almeida OP, Hogervorst E, Trompet S, Masaki K, Mooijaart SP, Gussekloo J, Peeters RP, Bauer DC, Aujesky D, Rodondi N | title = Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 101 | issue = 12 | pages = 4945–4954 | date = December 2016 | pmid = 27689250 | pmc = 6287525 | doi = 10.1210/jc.2016-2129 }}</ref> == History == [[Caleb Hillier Parry]] first made the association between the goiter and protrusion of the eyes in 1786, however, did not publish his findings until 1825.<ref>{{cite book|title=An Appraisal of Endocrinology |publisher=John and Mary R. Markle Foundation|date=1936 |page=9 |url=https://books.google.com/books?id=hFkrAAAAYAAJ&pg=PA9}}</ref> In 1835, Irish doctor [[Robert James Graves]] discovered a link between the protrusion of the eyes and goiter, giving his name to the autoimmune disease now known as Graves' Disease.{{cn|date=July 2024}} ==Pregnancy== {{see also|Thyroid disease in pregnancy}} Recognizing and evaluating hyperthyroidism in pregnancy is a diagnostic challenge.<ref>{{cite journal | vauthors = Fumarola A, Di Fiore A, Dainelli M, Grani G, Carbotta G, Calvanese A | title = Therapy of hyperthyroidism in pregnancy and breastfeeding | journal = Obstetrical & Gynecological Survey | volume = 66 | issue = 6 | pages = 378–385 | date = June 2011 | pmid = 21851752 | doi = 10.1097/ogx.0b013e31822c6388 | s2cid = 28728514 }}</ref> Thyroid hormones are commonly elevated during the first trimester of pregnancy as the pregnancy hormone [[human chorionic gonadotropin]] (hCG) stimulates thyroid hormone production, in a condition known as gestational transient thyrotoxicosis.<ref name="Lee 2023" /> Gestational transient thyrotoxicosis generally abates in the second trimester as hCG levels decline and thyroid function normalizes.<ref name="Lee 2023" /> Hyperthyroidism can increase the risk of complications for mother and child.<ref name = "Moleti_2019">{{cite journal | vauthors = Moleti M, Di Mauro M, Sturniolo G, Russo M, Vermiglio F | title = Hyperthyroidism in the pregnant woman: Maternal and fetal aspects | journal = Journal of Clinical & Translational Endocrinology | volume = 16 | pages = 100190 | date = June 2019 | pmid = 31049292 | pmc = 6484219 | doi = 10.1016/j.jcte.2019.100190 }}</ref> Such risks include pregnancy-related hypertension, pregnancy loss, low-birth weight, [[pre-eclampsia]], [[preterm]] delivery, still birth and behavioral disorders later in the child's life.<ref name="Lee 2023" /><ref>{{Cite journal | vauthors = Krassas GE |date=2010-10-01 |title=Thyroid Function and Human Reproductive Health |journal=Endocrine Reviews |series=Volume 31, Issue 5 |volume=31 |issue=5 |pages=702–755 |doi=10.1210/er.2009-0041|pmid=20573783 |doi-access=free }}</ref><ref name = "Moleti_2019" /><ref>{{cite journal | vauthors = Andersen SL, Andersen S, Vestergaard P, Olsen J | title = Maternal Thyroid Function in Early Pregnancy and Child Neurodevelopmental Disorders: A Danish Nationwide Case-Cohort Study | journal = Thyroid | volume = 28 | issue = 4 | pages = 537–546 | date = April 2018 | pmid = 29584590 | doi = 10.1089/thy.2017.0425 }}</ref> Nonetheless, high maternal FT4 levels during pregnancy have been associated with impaired brain developmental outcomes of the offspring and this was independent of hCG levels.<ref>{{cite journal | vauthors = Korevaar TI, Muetzel R, Medici M, Chaker L, Jaddoe VW, de Rijke YB, Steegers EA, Visser TJ, White T, Tiemeier H, Peeters RP | title = Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study | journal = The Lancet. Diabetes & Endocrinology | volume = 4 | issue = 1 | pages = 35–43 | date = January 2016 | pmid = 26497402 | doi = 10.1016/S2213-8587(15)00327-7 | hdl = 1765/79096 }}</ref> Propylthiouracil is the preferred [[antithyroid]] medication in the 1st trimester of pregnancy as it is less [[teratogenic]] than methimazole.<ref name="Lee 2023" /> ==Other animals== ===Cats=== {{main|Feline hyperthyroidism}} Hyperthyroidism is one of the most common endocrine conditions affecting older domesticated [[cat|housecats]]. In the United States, up to 10% of cats over ten years old have hyperthyroidism.<ref name="AAFP 2016">{{cite journal | vauthors = Carney HC, Ward CR, Bailey SJ, Bruyette D, Dennis S, Ferguson D, Hinc A, Rucinsky AR | title = 2016 AAFP Guidelines for the Management of Feline Hyperthyroidism | journal = Journal of Feline Medicine and Surgery | volume = 18 | issue = 5 | pages = 400–416 | date = May 2016 | pmid = 27143042 | doi = 10.1177/1098612X16643252 | doi-access = free | pmc = 11132203 }}</ref> The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. The most common cause of hyperthyroidism in cats is the presence of [[benign tumors]] called adenomas. 98% of cases are caused by the presence of an adenoma,<ref>Johnson, A. (2014). Small Animal Pathology for Veterinarian Technicians. Hoboken: Wiley Blackwell.</ref> but the reason these cats develop such tumors continues to be studied. The most common presenting symptoms are: rapid [[weight loss]], [[tachycardia]] (rapid heart rate), [[vomiting]], [[diarrhea]], increased consumption of fluids ([[polydipsia]]), increased appetite ([[polyphagia]]), and increased urine production ([[polyuria]]). Other symptoms include hyperactivity, possible aggression, an unkempt appearance, and large, thick [[claws]]. [[Heart murmurs]] and a [[gallop rhythm]] can develop due to secondary [[hypertrophic cardiomyopathy]]. About 70% of affected cats also have enlarged thyroid glands ([[goiter]]). 10% of cats exhibit "apathetic hyperthyroidism", which is characterized by anorexia and lethargy.<ref name=Gra2014>{{cite journal | vauthors = Vaske HH, Schermerhorn T, Armbrust L, Grauer GF | title = Diagnosis and management of feline hyperthyroidism: current perspectives | journal = Veterinary Medicine: Research and Reports | volume = 5 | pages = 85–96 | date = August 2014 | pmid = 32670849 | pmc = 7337209 | doi = 10.2147/VMRR.S39985 | doi-access = free }}</ref> The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). There is also a special low iodine diet available that will control the symptoms providing no other food is fed; Hill's y/d formula, when given exclusively, decreases T4 production by limiting the amount of iodine needed for thyroid hormone production. It is the only available commercial diet that focuses on managing feline hyperthyroidism. Medical and dietary management using methimazole and Hill's y/d cat food will give hyperthyroid cats an average of 2 years before dying due to secondary conditions such as heart and kidney failure.<ref name=Gra2014/> Drugs used to help manage the symptoms of hyperthyroidism are methimazole and carbimazole. Drug therapy is the least expensive option, even though the drug must be administered daily for the remainder of the cat's life. Carbimazole is only available as a once daily tablet. Methimazole is available as an oral solution, a tablet, and compounded as a [[topical medication|topical gel]] that is applied using a [[finger cot]] to the hairless skin inside a cat's ear. Many cat owners find this gel a good option for cats that don't like being given pills.{{cn|date=July 2024}} Radioiodine treatment, however, is not available in all areas, as this treatment requires nuclear radiological expertise and facilities that not only board the cat, but are specially equipped to manage the cat's urine, sweat, saliva, and stool, which are radioactive for several days after the treatment, usually for a total of 3 weeks (the cat spends the first week in total isolation and the next two weeks in close confinement).<ref>{{cite web| vauthors = Little S |title=Feline Hyperthyroidism |url=http://www.winnfelinehealth.org/Pages/Feline_Hyperthyroidism_Web.pdf |year=2006 |publisher=Winn Feline Foundation |access-date=24 June 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090509070957/http://www.winnfelinehealth.org/Pages/Feline_Hyperthyroidism_Web.pdf |archive-date=9 May 2009}}</ref> In the United States, the guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions.{{cn|date=July 2024}} ===Dogs=== Hyperthyroidism is much less common in [[dog]]s compared to cats.<ref>{{cite book| vauthors = Ford RB, Mazzaferro E |title=Kirk & Bistner's Handbook of Veterinary Procedures and Emergency Treatment|date=2011|publisher=Elsevier Health Sciences|location=London|isbn=978-1-4377-0799-1|page=346|edition=9th}}</ref> Hyperthyroidism may be caused by a thyroid tumor. This may be a thyroid [[carcinoma]]. About 90% of carcinomas are very aggressive; they invade the surrounding tissues and [[Metastasis|metastasize]] (spread) to other tissues, particularly the lungs. This has a poor [[prognosis]]. Surgery to remove the tumor is often very difficult due to [[metastasis]] into [[arteries]], the [[esophagus]], or the [[windpipe]]. It may be possible to reduce the size of the tumor, thus relieving symptoms and allowing time for other treatments to work.{{Citation needed|date=April 2010}} About 10% of thyroid tumors are benign; these often cause few symptoms.{{Citation needed|date=April 2010}} In dogs treated for [[hypothyroidism]] (lack of thyroid hormone), iatrogenic hyperthyroidism may occur as a result of an overdose of the thyroid hormone replacement medication, [[levothyroxine]]; in this case, treatment involves reducing the dose of levothyroxine.<ref name=HypoT>{{cite web|url=http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40602.htm|title=Hypothyroidism|publisher=Merck Veterinary Manual|access-date=27 July 2011|url-status=live|archive-url=https://web.archive.org/web/20110526152610/http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm%2Fbc%2F40602.htm|archive-date=26 May 2011}}</ref><ref>{{cite web|url=http://usa.leventa.com/Vet/label.asp|title=Leventa-Precautions/Adverse Reactions|publisher=Intervet|access-date=27 July 2011|url-status=live|archive-url=https://web.archive.org/web/20120114181242/http://usa.leventa.com/Vet/label.asp|archive-date=14 January 2012}}</ref> Dogs which display [[coprophagy]], the consumption of feces, and also live in a household with a dog receiving levothyroxine treatment, may develop hyperthyroidism if they frequently eat the feces from the dog receiving levothyroxine treatment.<ref name="Shadwick 2013">{{cite journal | vauthors = Shadwick SR, Ridgway MD, Kubier A | title = Thyrotoxicosis in a dog induced by the consumption of feces from a levothyroxine-supplemented housemate | journal = The Canadian Veterinary Journal | volume = 54 | issue = 10 | pages = 987–989 | date = October 2013 | pmid = 24155422 | pmc = 3781434 }}</ref> Hyperthyroidism may occur if a dog eats an excessive amount of thyroid gland tissue. This has occurred in dogs fed commercial dog food.<ref name="Broome 2015">{{cite journal | vauthors = Broome MR, Peterson ME, Kemppainen RJ, Parker VJ, Richter KP | title = Exogenous thyrotoxicosis in dogs attributable to consumption of all-meat commercial dog food or treats containing excessive thyroid hormone: 14 cases (2008-2013) | journal = Journal of the American Veterinary Medical Association | volume = 246 | issue = 1 | pages = 105–111 | date = January 2015 | pmid = 25517332 | doi = 10.2460/javma.246.1.105 | doi-access = free }}</ref> == See also == * [[High-output cardiac failure]] * [[Jod-Basedow phenomenon]] * [[Hashitoxicosis]] == References == {{Reflist}} == Further reading == {{refbegin}} * {{cite book | veditors = Brent GA | url = https://books.google.com/books?id=zxBqGlxwObYC | title = Thyroid Function Testing | location = New York | publisher = Springer | series = Endocrine Updates | volume = 28 | edition = 1st | date = 2010 | isbn = 978-1-4419-1484-2}} * {{Cite journal |vauthors=Ross DS, etal |title=2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis |doi=10.1089/thy.2016.0229 |journal=Thyroid |volume=26 |issue=10 |date=Oct 2016 |pages=1343–1421|pmid=27521067 |doi-access=free }} * {{Cite web | vauthors = Spadafori G| title=Hyperthyroidism: A Common Ailment in Older Cats | url=http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=138 | work=The Pet Connection | date=20 January 1997 | publisher=Veterinary Information Network | access-date=28 January 2007}} * {{Cite journal | vauthors = Siraj ES |date=June 2008 |title=Update on the Diagnosis and Treatment of Hyperthyroidism |journal=Journal of Clinical Outcomes Management |volume=15 |issue=6 |pages=298–307 |url=http://www.turner-white.com/memberfile.php?PubCode=jcom_jun08_hyperthyroidism.pdf |access-date=24 June 2009 |archive-url=https://web.archive.org/web/20131019153905/http://www.turner-white.com/memberfile.php?PubCode=jcom_jun08_hyperthyroidism.pdf |archive-date=19 October 2013 |url-status=dead }} {{refend}} == External links == * [http://www.merck.com/mmpe/sec12/ch152/ch152e.html#sec12-ch152-ch152e-239 Merck Manual article about hyperthyroidism] * [https://medlineplus.gov/hyperthyroidism.html Hyperthyroidism] at [[MedlinePlus]] {{Medical resources | DiseasesDB = 6348 | ICD11 = {{ICD11|5A02}} | ICD10 = {{ICD10|E05}} | ICD9 = {{ICD9|242.90}} | ICDO = | OMIM = | MedlinePlus = 000356 | eMedicineSubj = med | eMedicineTopic = 1109 | MeshID = D006980 }} {{Thyroid disease}} [[Category:Cat diseases]] [[Category:Dog diseases]] [[Category:Endocrine-related cutaneous conditions]] [[Category:Thyroid disease]] [[Category:Thyroid]] [[Category:Wikipedia emergency medicine articles ready to translate]] [[Category:Wikipedia medicine articles ready to translate]]
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