Editing Hypothyroidism

{{Short description|Insufficient production of thyroid hormones}}
{{Distinguish|Hyperthyroidism}}
{{good article}}
{{cs1 config|name-list-style=vanc}}
{{Infobox medical condition
| name          = Hypothyroidism
| image         = Thyroxine-2D-skeletal.png
| alt           = Molecular structure of the thyroxine molecule
| caption       = Molecular structure of thyroxine, which is deficient in hypothyroidism
| pronounce     = {{IPAc-en|ˌ|h|aɪ|p|ə|ˈ|θ|aɪ|r|ɔɪ|d|ɪ|z|əm|,_|-|p|oʊ|-}}{{refn|{{Dictionary.com|hypothyroidism}}}}{{refn|{{cite web |url=https://www.oxforddictionaries.com/definition/english/hypothyroidism |archive-url=https://web.archive.org/web/20130311062931/http://oxforddictionaries.com/definition/english/hypothyroidism |url-status=dead |archive-date=March 11, 2013 |title=hypothyroidism - definition of hypothyroidism in English from the Oxford dictionary |publisher=[[OxfordDictionaries.com]] |access-date=2016-01-20 }} }}
| synonyms      = Underactive thyroid, low thyroid, hypothyreosis
| field         = [[Endocrinology]]
| symptoms      = Fatigue (feeling tired), poor ability to tolerate cold, muscle aches, [[constipation]], weight gain,<ref name=NIH2025/> [[Depression (mood)|depression]], [[anxiety]], [[irritability]]<ref>{{Cite web|url=https://www.btf-thyroid.org/psychological-symptoms-and-thyroid-disorders|title=Psychological symptoms and thyroid disorders|website=British Thyroid Foundation|date=11 September 2019 }}</ref>
| complications = During [[pregnancy]] can result in [[cretinism]] in the baby<ref name=Pre2009/>
| onset         = > 60 years old<ref name=NIH2025/>
| duration      =
| causes        = [[Hashimoto's thyroiditis]], [[thyroiditis]], [[thyroidectomy|surgical removal of thyroid gland]], [[iodine deficiency]], [[lithium treatment]]<ref name=NIH2025/>
| risks         =
| diagnosis     = [[Blood test]]s ([[thyroid-stimulating hormone]], [[thyroxine]])<ref name=NIH2025/>
| differential  = [[Depression (mood)|Depression]], [[dementia]], [[heart failure]], [[chronic fatigue syndrome]]<ref>{{cite book|last1=Ferri|first1=Fred F.|title=Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders|date=2010|publisher=Elsevier/Mosby|location=Philadelphia, PA|isbn=978-0323076999|page=Chapter H|edition=2nd}}</ref>
| prevention    = [[iodised salt|Salt iodization]]<ref name=Sye2015/>
| treatment     = [[Levothyroxine]]<ref name=NIH2025/>
| medication    =
| prognosis     =
| frequency     = 0.3–0.4%<!--&nbsp;(overt); 4–5%&nbsp;(subclinical)--><ref name=Garber/>
| deaths        =
}}

<!-- Definition and symptoms -->
'''Hypothyroidism''' is an [[endocrine disease]] in which the [[thyroid gland]] does not produce enough [[thyroid hormone]]s.<ref name=NIH2025/> It can cause a number of symptoms, such as [[cold intolerance|poor ability to tolerate cold]], [[fatigue|extreme fatigue, muscle aches]], [[constipation]], [[slow heart rate]],  [[Depression (mood)|depression]], and [[weight gain]].<ref name=NIH2025/> Occasionally there may be swelling of the front part of the neck due to [[goiter]].<ref name=NIH2025>{{cite web|title=Hypothyroidism|url=https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism|website=National Institute of Diabetes and Digestive and Kidney Diseases|access-date=15 March 2025|date=March 2021|url-status=live|archive-url=https://web.archive.org/web/20250311214339/https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism|archive-date=11 March 2025}}</ref> Untreated cases of hypothyroidism during [[pregnancy]] can lead to delays in [[child development|growth and intellectual development]] in the baby or [[congenital iodine deficiency syndrome]].<ref name=Pre2009>{{cite book|last1=Preedy|first1=Victor|title=Comprehensive Handbook of Iodine Nutritional, Biochemical, Pathological and Therapeutic Aspects.|date=2009|publisher=Elsevier|location=Burlington|isbn=9780080920863|page=616|url=https://books.google.com/books?id=7v7g5XoCQQwC&pg=PA616}}</ref>

<!-- Cause and diagnosis -->
Worldwide, [[iodine deficiency|too little iodine]] in the diet is the most common cause of hypothyroidism.<ref name=Garber/><ref name=Chakera>{{cite journal | vauthors = Chakera AJ, Pearce SH, Vaidya B | title = Treatment for primary hypothyroidism: current approaches and future possibilities | journal = Drug Design, Development and Therapy | volume = 6 | pages = 1–11 | year = 2012 | pmid = 22291465 | pmc = 3267517 | doi = 10.2147/DDDT.S12894 | type = Review | doi-access = free }}</ref> [[Hashimoto's thyroiditis]], an autoimmune disease where the body's immune system reacts to the thyroid gland,<ref>{{cite web |title=Hashimoto's Disease |url=https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease |website=National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK) |access-date=2024-02-19}}</ref> is the most common cause of hypothyroidism in countries with sufficient dietary iodine.<ref name=NIH2025/> Less common causes include previous treatment with [[iodine-131|radioactive iodine]], injury to the [[hypothalamus]] or the [[anterior pituitary]] gland, certain medications, [[congenital hypothyroidism|a lack of a functioning thyroid at birth]], or previous [[thyroidectomy|thyroid surgery]].<ref name=NIH2025/><ref name=Persani2012>{{cite journal | vauthors = Persani L | title = Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 9 | pages = 3068–78 | date = September 2012 | pmid = 22851492 | doi = 10.1210/jc.2012-1616 | type = Review | doi-access = free }}</ref> The diagnosis of hypothyroidism, when suspected, can be confirmed with [[blood test]]s measuring [[thyroid-stimulating hormone]] (TSH) and [[thyroxine]] (T4) levels.<ref name=NIH2025/>

<!-- Prevention and teatment -->
[[Iodised salt|Salt iodization]] has prevented hypothyroidism in many populations.<ref name=Sye2015>{{cite journal | vauthors = Syed S | title = Iodine and the "near" eradication of cretinism | journal = Pediatrics | volume = 135 | issue = 4 | pages = 594–6 | date = April 2015 | pmid = 25825529 | doi = 10.1542/peds.2014-3718 | doi-access =  | s2cid = 27647943 }}</ref> Thyroid hormone replacement with [[levothyroxine]] treats hypothyroidism.<ref name=NIH2025/> Medical professionals adjust the dose according to symptoms and normalization of the TSH levels.<ref name=NICENG145/> Thyroid medication is safe in pregnancy.<ref name=NIH2025/> Although an adequate amount of dietary iodine is important, too much may worsen specific forms of hypothyroidism.<ref name=NIH2025/>

<!-- Epidemiology and culture -->
Worldwide about one billion people are estimated to be iodine-deficient; however, it is unknown how often this results in hypothyroidism.<ref name=WernerIngbar>{{cite book|title=Werner & Ingbar's the thyroid: a fundamental and clinical text|publisher=Wolters Kluwer/Lippincott Williams & Wilkins Health|location=Philadelphia|isbn=978-1451120639|page=552|url=https://books.google.com/books?id=DaNIXqNLmXsC&pg=PA552|edition=10th|editor1=Cooper, DS|editor2=Braverman LE|date=2012-07-12|url-status=live|archive-url=https://web.archive.org/web/20160520160442/https://books.google.com/books?id=DaNIXqNLmXsC&pg=PA552|archive-date=2016-05-20}}</ref> In the United States, overt hypothyroidism occurs in approximately 0.3–0.4% of people.<ref name=Garber/> Subclinical hypothyroidism, a milder form of hypothyroidism characterized by normal thyroxine levels and an elevated TSH level, is thought to occur in 4.3–8.5% of people in the United States.<ref name=Garber>{{cite journal | vauthors = Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA | title = Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association | journal = Thyroid | volume = 22 | issue = 12 | pages = 1200–35 | date = December 2012 | pmid = 22954017 | doi = 10.1089/thy.2012.0205 }}</ref> Hypothyroidism is more common in women than in men.<ref name=NIH2025/> People over the age of 60 are more commonly affected.<ref name=NIH2025/> Dogs are also known to develop hypothyroidism, as are cats and horses, albeit more rarely.<ref name=Merck>{{cite web | title=Hypothyroidism | work=Merck Veterinary Manual, 10th edition (online version) | url=http://www.merckmanuals.com/vet/endocrine_system/the_thyroid_gland/hypothyroidism.html | year=2012 | access-date=2013-12-25 | url-status=live | archive-url=https://web.archive.org/web/20120823162629/http://www.merckmanuals.com/vet/endocrine_system/the_thyroid_gland/hypothyroidism.html | archive-date=2012-08-23 }}</ref> The word ''hypothyroidism'' is from  Greek ''hypo-'' 'reduced',  ''thyreos'' 'shield', and ''eidos'' 'form', where the two latter parts refer to the [[Thyroid|thyroid gland]].<ref>{{cite book|title=Mosby's Medical Dictionary|date=2013|publisher=Elsevier Health Sciences|isbn=9780323112581|page=887|edition=9|url=https://books.google.com/books?id=aW0zkZl0JgQC&pg=PA887|url-status=live|archive-url=https://web.archive.org/web/20160307010245/https://books.google.ca/books?id=aW0zkZl0JgQC&pg=PA887|archive-date=2016-03-07}}</ref>
{{TOC limit|3}}

== Signs and symptoms ==
People with hypothyroidism often have no or only mild symptoms. Numerous symptoms and [[medical sign|signs]] are associated with hypothyroidism and can be related to the underlying cause, or a direct effect of not having enough thyroid hormones.<ref name=Longo>{{cite book | vauthors = Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J |title=Harrison's principles of internal medicine.|year=2011|publisher=McGraw-Hill|location=New York|isbn=978-0071748896|edition=18th|chapter=341: disorders of the thyroid gland}}</ref><ref name=Khandelwal2012/> Many symptoms of hypothyroidism are otherwise common and do not necessarily indicate thyroid problem.<ref name=NIH2025/> [[Hashimoto's thyroiditis]] may present with the [[Mass effect (medicine)|mass effect]] of a [[goiter]] (enlarged thyroid gland).<ref name=Longo/> In middle-aged women, the symptoms may be mistaken for those of [[menopause]].<ref name=NICENG145>{{cite web |title=Thyroid disease: assessment and management |url=https://www.nice.org.uk/guidance/ng145 |website=www.nice.org.uk |publisher=[[National Institute for Health and Care Excellence]] |access-date=15 March 2025 |date=12 October 2023}}</ref>

[[File:Signs and symptoms of hypothyroidism.png|thumb|300px|Symptoms and signs of hypothyroidism<ref name=Longo/>]]
{|class="wikitable" style = "margin-left:15px; text-align:center"
! Symptoms<ref name=Longo/>
! Signs<ref name=Longo/>
|-
| [[Fatigue]]
| Dry, coarse skin
|-
| Feeling cold
| Cool extremities
|-
| Poor memory and concentration
| [[Myxedema]] ([[mucopolysaccharide]] deposits in the skin)
|-
| [[Constipation]], [[dyspepsia]]<ref name="Ebert2010">{{cite journal | vauthors = Ebert EC | title = The thyroid and the gut | journal = Journal of Clinical Gastroenterology | volume = 44 | issue = 6 | pages = 402–6 | date = July 2010 | pmid = 20351569 | doi = 10.1097/MCG.0b013e3181d6bc3e | s2cid = 23210397 }}</ref>
| [[Hair loss]], [[Sign of Hertoghe]]
|-
| Weight gain with poor appetite
| [[Bradycardia|Slow pulse rate]]
|-
| [[Shortness of breath]]
| [[Edema|Swelling]] of the limbs
|-
| [[Hoarse voice]]
| Delayed relaxation of [[tendon reflex]]es
|-
| In females, [[Menorrhagia|heavy menstrual period]]s (and later [[oligomenorrhea|light periods]])
| [[Carpal tunnel syndrome]]
|-
| [[Paresthesia|Abnormal sensation]]
| [[Pleural effusion]], [[ascites]], [[pericardial effusion]]
|-
| [[Hearing loss|Poor hearing]]
|
|-
|[[Muscle weakness]]
|}

Delayed relaxation after testing the [[ankle jerk reflex]] is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit.<ref name=Garber/>

===Myxedema coma===
{{Multiple image
<!-- Essential parameters -->
| align     = right
| direction = horizontal
| width     = 175
<!-- Image 1 -->
| image1    = Myxedema face.png
| caption1  = Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes, and pallor
<!-- Image 2 -->
| image2    = Myxedema standing.png
| caption2  = Additional symptoms include swelling of the arms and legs and [[ascites]].}}
[[Myxedema coma]] is a rare but life-threatening state of extreme hypothyroidism.<!-- <ref name=Klubo/> --> It may occur in those with established hypothyroidism when they develop an acute illness. Myxedema coma can be the first presentation of hypothyroidism.<!-- <ref name=Klubo/> --> People with myxedema coma typically have a [[hypothermia|low body temperature]] without shivering, [[altered level of consciousness|confusion]], a [[Bradycardia|slow heart rate]] and [[Hypoventilation|reduced breathing effort]].<!-- <ref name=Klubo/> --> There may be physical signs suggestive of hypothyroidism, such as skin changes or [[Macroglossia|enlargement of the tongue]].<ref name=Klubo>{{cite journal | vauthors = Klubo-Gwiezdzinska J, Wartofsky L | title = Thyroid emergencies | journal = The Medical Clinics of North America | volume = 96 | issue = 2 | pages = 385–403 | date = March 2012 | pmid = 22443982 | doi = 10.1016/j.mcna.2012.01.015 }}</ref>

===Pregnancy===
{{Main|Thyroid disease in women}}
Hypothyroidism when untreated may lead to [[infertility]] and an increased risk of [[miscarriage]] or [[perinatal mortality|infant death around the time of birth]], mostly in severe cases of hypothyroidism.<ref name=NIH2017>{{cite web|title=Thyroid disease in Women|url=https://www.niddk.nih.gov/health-information/endocrine-diseases/pregnancy-thyroid-disease|publisher=Office on Women's Health, U.S. Department of Health and Human Services|access-date=15 March 2025|date=December 2017|url-status=live|archive-url=https://web.archive.org/web/20250304231739/https://www.niddk.nih.gov/health-information/endocrine-diseases/pregnancy-thyroid-disease|archive-date=4 March 2025}}{{PD-notice}}</ref><ref>{{cite web | title =Postpartum Thyroiditis | publisher = American Thyroid Association | access-date = 20 July 2017 | date = 2014| url = http://www.thyroid.org/wp-content/uploads/patients/brochures/Postpartum_Thyroiditis_brochure.pdf}}</ref> [[Thyroid disease in pregnancy|Women are affected by hypothyroidism]] in 0.3–0.5% of pregnancies.<ref name=Vissenberg2012>{{cite journal | vauthors = Vissenberg R, van den Boogaard E, van Wely M, van der Post JA, Fliers E, Bisschop PH, Goddijn M | title = Treatment of thyroid disorders before conception and in early pregnancy: a systematic review | journal = Human Reproduction Update | volume = 18 | issue = 4 | pages = 360–73 | date = July 2012 | pmid = 22431565 | doi = 10.1093/humupd/dms007 | type = Review | doi-access = free }}</ref> Subclinical hypothyroidism during pregnancy is associated with [[preterm birth|birth of the baby before 37 weeks of pregnancy]].<ref>{{cite journal | vauthors = Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S | title = 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum | journal = Thyroid | volume = 27 | issue = 3 | pages = 315–389 | date = March 2017 | pmid = 28056690 | doi = 10.1089/thy.2016.0457 | pmc = 3472679 | doi-access = free }}</ref>

===Children===
Newborn children with hypothyroidism may have normal birth weight and height (although the head may be larger than expected and the [[posterior fontanelle]] may be open).<!-- <ref name=Counts> --> Some may have drowsiness, [[Hypotonia|decreased muscle tone]], poor weight gain, a hoarse-sounding cry, feeding difficulties, constipation, an [[macroglossia|enlarged tongue]], [[umbilical hernia]], [[Xeroderma|dry skin]], a [[Hypothermia|decreased body temperature]], and [[Neonatal jaundice|jaundice]].<ref name=Counts>{{cite journal | vauthors = Counts D, Varma SK | title = Hypothyroidism in children | journal = Pediatrics in Review | volume = 30 | issue = 7 | pages = 251–8 | date = July 2009 | pmid = 19570923 | doi = 10.1542/pir.30-7-251 | s2cid = 29460139 }}</ref> A [[goiter]] is rare, although it may develop later in children who have a thyroid gland that does not produce [[thyroid dyshormonogenesis|functioning thyroid hormone]].<ref name=Counts/> A goiter may also develop in children growing up in areas with [[iodine deficiency]].<ref name=Pearce>{{cite journal | vauthors = Pearce EN | title = Update in lipid alterations in subclinical hypothyroidism | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 2 | pages = 326–33 | date = February 2012 | pmid = 22205712 | doi = 10.1210/jc.2011-2532 | doi-access = free }}</ref> Normal growth and development may be delayed, and not treating infants may lead to an intellectual impairment (IQ 6–15 points lower in severe cases).<!-- <ref name=Counts/> --> Other problems include the following: difficulty with large scale and fine [[motor skill]]s and [[ataxia|coordination]], reduced muscle tone, [[Strabismus|squinting]], decreased [[attention span]], and [[speech acquisition|delayed speaking]].<ref name=Counts/> [[Tooth eruption]] may be delayed.<ref>{{cite journal | vauthors = Chandna S, Bathla M | title = Oral manifestations of thyroid disorders and its management | journal = Indian Journal of Endocrinology and Metabolism | volume = 15 | issue = Suppl 2 | pages = S113–6 | date = July 2011 | pmid = 21966646 | pmc = 3169868 | doi = 10.4103/2230-8210.83343 | doi-access = free }}</ref>

In older children and adolescents, the symptoms of hypothyroidism may include fatigue, cold intolerance, sleepiness, muscle weakness, constipation, a delay in growth, overweight for height, pallor, coarse and thick skin, [[Hypertrichosis|increased body hair]], [[Irregular menstruation|irregular menstrual cycles]] in girls, and [[delayed puberty]]. Signs may include delayed relaxation of the ankle reflex and a [[bradycardia|slow heartbeat]].<ref name=Counts/> A goiter may be present with a completely enlarged thyroid gland;<ref name=Counts/> sometimes only part of the thyroid is enlarged and it can be knobby.<ref name=Brown2013>{{cite journal | vauthors = Brown RS | title = Autoimmune thyroiditis in childhood | journal = Journal of Clinical Research in Pediatric Endocrinology | volume = 5 Suppl 1 | issue = 4 | pages = 45–9 | year = 2013 | pmid = 23154164 | pmc = 3608006 | doi = 10.4274/jcrpe.855 | type = Review }}</ref>

==Causes==
Hypothyroidism is caused by inadequate function of the gland itself (primary hypothyroidism), inadequate stimulation by [[thyroid-stimulating hormone]] from the [[pituitary gland]] (secondary hypothyroidism), or inadequate release of [[thyrotropin-releasing hormone]] from the brain's [[hypothalamus]] (tertiary hypothyroidism).<ref name="Garber" /><ref name="Gaitonde2012">{{cite journal | vauthors = Gaitonde DY, Rowley KD, Sweeney LB | title = Hypothyroidism: an update | journal = American Family Physician | volume = 86 | issue = 3 | pages = 244–51 | date = August 2012 | pmid = 22962987 | url = https://www.aafp.org/linked_out?pmid=22962987 }}{{Dead link|date=August 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Primary hypothyroidism is about a thousandfold more common than central hypothyroidism.<ref name="Persani2012" /> Central hypothyroidism is the name used for secondary and tertiary hypothyroidism since the hypothalamus and pituitary gland are at the center of thyroid hormone control.

[[Iodine deficiency]] is the most common cause of primary hypothyroidism and [[endemic goiter]] worldwide.<ref name=Garber/><ref name=Chakera/> In areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease [[Hashimoto's thyroiditis]] (chronic autoimmune thyroiditis).<ref name=Garber/><ref name=Chakera/> Hashimoto's may be associated with a goiter. It is characterized by infiltration of the thyroid gland with [[T cell|T lymphocytes]] and [[autoantibody|autoantibodies]] [[Anti-thyroid autoantibodies|against specific thyroid antigens]] such as [[thyroid peroxidase]], [[thyroglobulin]] and the [[thyrotropin receptor|TSH receptor]].<ref name=Garber/>

After women give birth, about 5% develop [[postpartum thyroiditis]] which can occur up to nine months afterwards.<ref name="Stagnaro2012"/> This is characterized by a short period of [[hyperthyroidism]] followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.<ref name="Stagnaro2012">{{cite journal | vauthors = Stagnaro-Green A | title = Approach to the patient with postpartum thyroiditis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 2 | pages = 334–42 | date = February 2012 | pmid = 22312089 | doi = 10.1210/jc.2011-2576 | type = Review | doi-access = free }}</ref>

[[Hashimoto's thyroiditis|Autoimmune thyroiditis (Hashimoto's)]] is associated with other [[autoimmune disease|immune-mediated diseases]] such as [[diabetes mellitus type 1]], [[pernicious anemia]], [[myasthenia gravis]], [[celiac disease]], [[rheumatoid arthritis]] and [[systemic lupus erythematosus]].<ref name=Garber/> It may occur as part of [[autoimmune polyendocrine syndrome]] ([[Autoimmune polyendocrine syndrome type 1|type 1]] and [[Autoimmune polyendocrine syndrome type 2|type 2]]).<ref name=Garber/>

[[Iatrogenesis|Iatrogenic]] hypothyroidism can be surgical (a result of [[thyroidectomy]], usually for [[thyroid nodule]]s or [[Thyroid cancer|cancer]]) or following [[radioiodine]] ablation (usually for [[Graves' disease]]).

{|class="wikitable" style = "margin-left:15px; text-align:center"
! Type of hypothyroidism
! Causes
|-
| Primary hypothyroidism<ref name=Garber/>
| Iodine deficiency (developing countries), autoimmune thyroiditis, [[subacute granulomatous thyroiditis]], [[subacute lymphocytic thyroiditis]], [[postpartum thyroiditis]], previous [[thyroidectomy]], [[acute infectious thyroiditis]],<ref name="Shrestha2015">{{cite book |last1=Shrestha |first1=ST |last2=Hennessey |first2=J |title=Acute and Subacute, and Riedel's Thyroiditis |date=December 2015 |publisher=MDText.com, Inc |pmid=25905408 |url=https://www.ncbi.nlm.nih.gov/books/NBK285553/}}</ref> previous [[Iodine-131|radioiodine]] treatment, previous [[external beam radiotherapy]] to the neck<br />Medication: [[Lithium pharmacology|lithium]]-based [[mood stabilizer]]s, [[amiodarone]], [[interferon alpha]], [[Tyrosine-kinase inhibitor|tyrosine kinase inhibitors]] such as [[sunitinib]]
|-
| Central hypothyroidism<ref name=Persani2012/>
| Lesions compressing the pituitary ([[pituitary adenoma]], [[craniopharyngioma]], [[meningioma]], [[glioma]], [[Rathke's cleft cyst]], [[metastasis]], [[empty sella syndrome|empty sella]], [[intracranial aneurysm|aneurysm]] of the [[internal carotid artery]]), surgery or radiation to the pituitary, drugs, injury, vascular disorders ([[pituitary apoplexy]], [[Sheehan syndrome]], [[subarachnoid hemorrhage]]), autoimmune diseases ([[lymphocytic hypophysitis]], polyglandular disorders), infiltrative diseases (iron overload due to [[hemochromatosis]] or [[Beta-thalassemia|thalassemia]], [[neurosarcoidosis]], [[Langerhans cell histiocytosis]]), particular inherited congenital disorders, and infections ([[tuberculosis]], [[mycosis|mycoses]], [[syphilis]])
|-
| [[Congenital hypothyroidism]]<ref name="Donaldson2013">{{cite journal | vauthors = Donaldson M, Jones J | title = Optimising outcome in congenital hypothyroidism; current opinions on best practice in initial assessment and subsequent management | journal = Journal of Clinical Research in Pediatric Endocrinology | volume = 5 Suppl 1 | issue = 4 | pages = 13–22 | year = 2013 | pmid = 23154163 | pmc = 3608009 | doi = 10.4274/jcrpe.849 | type = Review }}</ref>
| [[Thyroid dysgenesis]] (75%), [[thyroid dyshormonogenesis]] (20%), maternal antibody or radioiodine transfer<br />Syndromes: mutations (in ''[[GNAS complex locus]]'', ''[[PAX8]]'', ''[[NK2 homeobox 1|TTF-1/NKX2-1]]'', ''[[FOXE1|TTF-2/FOXE1]]''), [[Pendred's syndrome]] (associated with [[sensorineural hearing loss]])<br />Transiently: due to maternal iodine deficiency or excess, anti-TSH receptor antibodies, certain congenital disorders, neonatal illness<br />Central: pituitary dysfunction (idiopathic, [[septo-optic dysplasia]], deficiency of ''[[Pituitary-specific positive transcription factor 1|PIT1]]'', isolated TSH deficiency)
|}

==Pathophysiology==
[[File:Thyroid system.svg|right|thumb|alt=Diagram of a person with a large blue arrow representing the actions of thyroxine on the body and a green and red arrow representing actions of TSH and TRH respectively |Diagram of the hypothalamic–pituitary–thyroid axis. The hypothalamus secretes TRH (green), which stimulates the pituitary gland to produce TSH (red). This, in turn, stimulates the production of thyroxine by the thyroid (blue). Thyroxine levels decrease TRH and TSH production by a negative feedback process.]]

Thyroid hormone is required for the normal functioning of numerous tissues in the body. In healthy individuals, the thyroid gland predominantly secretes thyroxine (T<sub>4</sub>), which is converted into [[triiodothyronine]] (T<sub>3</sub>) in other organs by the [[selenium]]-dependent enzyme [[iodothyronine deiodinase]].<ref>{{cite journal | vauthors = Maia AL, Goemann IM, Meyer EL, Wajner SM | title = Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease | journal = The Journal of Endocrinology | volume = 209 | issue = 3 | pages = 283–97 | date = June 2011 | pmid = 21415143 | doi = 10.1530/JOE-10-0481 | doi-access = free }}</ref> Triiodothyronine binds to the [[thyroid hormone receptor]] in the [[Cell nucleus|nucleus]] of cells, where it stimulates the [[Transcription (genetics)|turning on]] of particular [[gene]]s and the production of specific proteins.<ref name=Cheng>{{cite journal | vauthors = Cheng SY, Leonard JL, Davis PJ | title = Molecular aspects of thyroid hormone actions | journal = Endocrine Reviews | volume = 31 | issue = 2 | pages = 139–70 | date = April 2010 | pmid = 20051527 | pmc = 2852208 | doi = 10.1210/er.2009-0007 }}</ref> Additionally, the hormone binds to [[Alpha-v beta-3|integrin αvβ3]] on the [[cell membrane]], thereby stimulating the [[sodium–hydrogen antiporter]] and processes such as [[angiogenesis|formation of blood vessels]] and [[cell growth]].<ref name=Cheng/> In blood, almost all thyroid hormone (99.97%) are bound to plasma proteins such as [[thyroxine-binding globulin]]; only the free unbound thyroid hormone is biologically active.<ref name=Garber/>

[[Electrocardiography|Electrocardiograms]] are abnormal in both primary overt hypothyroidism and subclinical hypothyroidism.<ref name="pmid38019451" /> T3 and TSH are essential for the regulation of cardiac electrical activity.<ref name="pmid38019451" /> Prolonged ventricular repolarization and [[atrial fibrillation]] are often seen in hypothyroidism.<ref name="pmid38019451" />

The thyroid gland is the only source of thyroid hormone in the body; the process requires [[iodine]] and the [[amino acid]] [[tyrosine]]. The gland takes up iodine in the bloodstream and incorporates it into [[thyroglobulin]] molecules. The process is controlled by the [[thyroid-stimulating hormone]] (TSH, thyrotropin), which is secreted by the [[pituitary gland|pituitary]]. Not enough iodine, or not enough TSH, can decrease thyroid hormone production.<ref name=Gaitonde2012/>

The [[hypothalamic–pituitary–thyroid axis]] plays a key role in maintaining thyroid hormone levels within normal limits. Production of TSH by the anterior pituitary gland is stimulated in turn by [[thyrotropin-releasing hormone]] (TRH), released from the hypothalamus. Production of TSH and TRH is decreased by thyroxine by a [[negative feedback]] process. Not enough TRH, which is uncommon, can lead to insufficient TSH release and therefore insufficient thyroid hormone production.<ref name=Persani2012/>

Pregnancy leads to marked changes in thyroid hormone physiology. The gland increases in size by 10%, thyroxine production increases by 50%, and iodine requirements increase. Many women have normal thyroid function but have immunological evidence of thyroid autoimmunity (as evidenced by autoantibodies) or are iodine deficient, and develop evidence of hypothyroidism before or after giving birth.<ref name=Stagnaro>{{cite journal | vauthors = Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W | title = Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum | journal = Thyroid | volume = 21 | issue = 10 | pages = 1081–125 | date = October 2011 | pmid = 21787128 | pmc = 3472679 | doi = 10.1089/thy.2011.0087 }}</ref>

==Diagnosis==
{{See also|Thyroid function tests}}
Laboratory testing of thyroid stimulating hormone (TSH) levels in the blood is considered the best initial test for hypothyroidism; a second TSH level is often obtained several weeks later for confirmation.<ref name=So2012>{{cite journal | vauthors = So M, MacIsaac RJ, Grossmann M | title = Hypothyroidism | journal = Australian Family Physician | volume = 41 | issue = 8 | pages = 556–62 | date = August 2012 | pmid = 23145394 | url = https://gplearning.racgp.org.au/content/AFP/12Aug/August_focus_so.pdf }}</ref> Levels may be abnormal in the context of other illnesses, and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected<ref name=Garber/> as the cause of the acute illness.<ref name=NICENG145/> An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone, and free T<sub>4</sub> levels are then often obtained.<ref name=Garber/><ref name=NICENG145/><ref name=Brown2013/> Measuring T<sub>3</sub> in the assessment for hypothyroidism is discouraged by the [[American Association of Clinical Endocrinologists]] (AACE) and [[National Institute for Health and Care Excellence]] (NICE).<ref name=Garber/> NICE recommends routine T<sub>4</sub> testing in children where clinically indicated, and in adults only if central hypothyroidism is suspected or the TSH is abnormal.<ref name=NICENG145/> There are several symptom rating scales for hypothyroidism; they provide a degree of objectivity but have limited use for diagnosis.<ref name=Garber/>

{| class="wikitable" style="float: right; border: 1px solid #BBB; margin: .46em 0 0 .2em;"
|-
! TSH !! T<sub>4</sub> !! Interpretation
|-
| Normal || Normal || Normal thyroid function
|-
| Elevated || Low || Overt hypothyroidism
|-
| Normal/low || Low || Central hypothyroidism
|-
| Elevated || Normal || Subclinical hypothyroidism
|}

Many cases of hypothyroidism are associated with mild elevations in [[creatine kinase]] and liver enzymes in the blood. They typically return to normal when hypothyroidism has been fully treated.<ref name=Garber/> Levels of [[cholesterol]], [[low-density lipoprotein]] and [[lipoprotein(a)|lipoprotein (a)]] can be elevated;<ref name=Garber/> the impact of subclinical hypothyroidism on lipid parameters is less well-defined.<ref name=Pearce/>

Very severe hypothyroidism and myxedema coma are characteristically associated with [[hyponatremia|low sodium levels in the blood]] together with elevations in [[Vasopressin|antidiuretic hormone]], as well as [[Acute kidney injury|acute worsening of kidney function]] due to several causes.<ref name=Klubo/> For most causes, however, it is unclear if the relationship is causal.<ref>{{cite journal | vauthors = Pantalone KM, Hatipoglu BA | title = Hyponatremia and the Thyroid: Causality or Association? | journal = Journal of Clinical Medicine | volume = 4 | issue = 1 | pages = 32–6 | date = December 2014 | pmid = 26237016 | pmc = 4470237 | doi = 10.3390/jcm4010032 | doi-access = free }}</ref>

A diagnosis of hypothyroidism without any [[Thyroid nodule|lumps or masses]] [[Palpation|felt]] within the thyroid gland does not require thyroid imaging; however, if the thyroid feels abnormal, diagnostic imaging is then recommended.<ref name=So2012/> The presence of antibodies against [[thyroid peroxidase]] (TPO) makes it more likely that thyroid nodules are caused by autoimmune thyroiditis, but if there is any doubt, a [[fine-needle aspiration|needle biopsy]] may be required.<ref name=Garber/>

===Central===
If the TSH level is normal or low and serum free T<sub>4</sub> levels are low, this is suggestive of '''central hypothyroidism''' (not enough TSH or TRH secretion by the pituitary gland or hypothalamus, respectively). There may be other features of [[hypopituitarism]], such as [[menstrual cycle]] abnormalities and [[adrenal insufficiency]]. There might also be symptoms of a [[pituitary adenoma|pituitary mass]] such as [[headache]]s and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause.<ref name=Persani2012/><ref name=So2012/>

===Overt===
In overt primary hypothyroidism, TSH levels are high and T<sub>4</sub> levels are low. Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU/L, appropriate symptoms, and only a borderline low T<sub>4</sub>.<ref name=Don2009>{{cite book|last1=Dons|first1=Robert F.|last2=Wians|first2=Frank H. Jr.|title=Endocrine and metabolic disorders clinical lab testing manual|date=2009|publisher=CRC Press|location=Boca Raton|isbn=9781420079364|page=10|edition=4th|url=https://books.google.com/books?id=rS41IwpI-hIC&pg=PA10}}</ref> It may also be diagnosed in those with a TSH of greater than 10mIU/L.<ref name=Don2009/>

===Subclinical===
Subclinical hypothyroidism is a biochemical diagnosis characterized by an elevated serum TSH level, but with a normal serum free thyroxine level.<ref name="Peters 2017">{{cite journal |last1=Peeters |first1=Robin P. |title=Subclinical Hypothyroidism |journal=New England Journal of Medicine |date=29 June 2017 |volume=376 |issue=26 |pages=2556–2565 |doi=10.1056/NEJMcp1611144|pmid=28657873 |s2cid=56184355 }}</ref><ref name=Bona2013>{{cite journal | vauthors = Bona G, Prodam F, Monzani A | title = Subclinical hypothyroidism in children: natural history and when to treat | journal = Journal of Clinical Research in Pediatric Endocrinology | volume = 5 Suppl 1 | issue = 4 | pages = 23–8 | year = 2013 | pmid = 23154159 | pmc = 3608012 | doi = 10.4274/jcrpe.851 | type = Review }}</ref><ref name=Fatourechi/> The incidence of subclinical hypothyroidism is estimated to be 3-15% and a higher incidence is seen in elderly people, females and those with lower iodine levels.<ref name="Peters 2017" /> Subclinical hypothyroidism is most commonly caused by autoimmune thyroid diseases, especially [[Hashimoto's thyroiditis]].<ref name=Baumgartner2014>{{cite journal | vauthors = Baumgartner C, Blum MR, Rodondi N | title = Subclinical hypothyroidism: summary of evidence in 2014 | journal = [[Swiss Medical Weekly]] | volume = 144 | pages = w14058 | date = December 2014 | pmid = 25536449 | doi = 10.4414/smw.2014.14058 | type = Review | doi-access = free }}</ref>  The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed.<ref name=Bona2013/> Of people with subclinical hypothyroidism, a proportion will develop overt hypothyroidism each year. In those with detectable antibodies against thyroid peroxidase (TPO), this occurs in 4.3%, while in those with no detectable antibodies, this occurs in 2.6%.<ref name=Garber/> In addition to detectable anti-TPO antibodies, other risk factors for conversion from subclinical hypothyroidism to overt hypothyroidism include female sex or in those with higher TSH levels or lower level of normal free T<sub>4</sub> levels.<ref name="Peters 2017" /> Those with subclinical hypothyroidism and detectable anti-TPO antibodies who do not require treatment should have repeat thyroid function tested more frequently (e.g. every 6 months) compared with those who do not have antibodies.<ref name=So2012/><ref name="Peters 2017" />

===Pregnancy===
During pregnancy, the thyroid gland must produce 50% more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother.<ref name="Negro2014">{{cite journal | vauthors = Negro R, Stagnaro-Green A | title = Diagnosis and management of subclinical hypothyroidism in pregnancy | journal = BMJ | volume = 349 | issue = 10 | pages = g4929 | date = October 2014 | pmid = 25288580 | doi = 10.1136/bmj.g4929 | s2cid = 21104809 }}</ref>  In pregnancy, free thyroxine levels may be lower than anticipated due to increased binding to [[thyroid binding globulin]] and decreased binding to [[albumin]]. They should either be corrected for the stage of pregnancy,<ref name=Stagnaro/> or total thyroxine levels should be used instead for diagnosis.<ref name=Garber/> TSH values may also be lower than normal (particularly in the [[first trimester]]) and the normal range should be adjusted for the stage of pregnancy.<ref name=Garber/><ref name=Stagnaro/>

In pregnancy, subclinical hypothyroidism is defined as a TSH between 2.5 and 10&nbsp;mIU/L with a normal thyroxine level, while those with TSH above 10&nbsp;mIU/L are considered to be overtly hypothyroid even if the thyroxine level is normal.<ref name=Stagnaro/> Antibodies against TPO may be important in making treatment decisions, and should, therefore, be determined in women with abnormal thyroid function tests.<ref name=Garber/> Determination of TPO antibodies may be considered as part of the assessment of [[recurrent miscarriage]], as subtle thyroid dysfunction can be associated with pregnancy loss,<ref name="Garber" /> but this recommendation is not universal,<ref>{{cite journal | title = Evaluation and treatment of recurrent pregnancy loss: a committee opinion | journal = Fertility and Sterility | volume = 98 | issue = 5 | pages = 1103–11 | date = November 2012 | pmid = 22835448 | doi = 10.1016/j.fertnstert.2012.06.048 | author1 = Practice Committee of the American Society for Reproductive Medicine | s2cid = 30527688 | doi-access = free }}</ref> and the presence of thyroid antibodies may not predict future outcomes.<ref name="RCOG">{{cite web |title=Recurrent Miscarriage, Investigation and Treatment of Couples |url=https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg17/ |website=Royal College of Obstetricians & Gynaecologists }}</ref>

==Prevention==
[[File:CDpic1.png|thumb|right|A 3-month-old infant with untreated [[congenital hypothyroidism]] showing myxedematous facies, a big tongue, and skin mottling]]
Hypothyroidism may be prevented in a population by adding iodine to commonly used foods. This public health measure has eliminated endemic childhood hypothyroidism in countries where it was once common. In addition to promoting the consumption of iodine-rich foods such as dairy and fish, many countries with moderate [[iodine deficiency]] have implemented universal [[salt iodization]].<ref name=Charlton>{{cite journal | vauthors = Charlton K, Skeaff S | title = Iodine fortification: why, when, what, how, and who? | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 14 | issue = 6 | pages = 618–24 | date = November 2011 | pmid = 21892078 | doi = 10.1097/MCO.0b013e32834b2b30 | s2cid = 22906831 }}</ref> Encouraged by the [[World Health Organization]],<ref>{{cite book|vauthors = (([[World Health Organization]], [[UNICEF]], [[ICCIDD]]))|title=Assessment of iodine deficiency disorders and monitoring their elimination|year=2008|publisher=World Health Organization|location=Geneva|isbn=9789241595827|url=http://whqlibdoc.who.int/publications/2007/9789241595827_eng.pdf|edition=3rd|url-status=live|archive-url=https://web.archive.org/web/20131228223822/http://whqlibdoc.who.int/publications/2007/9789241595827_eng.pdf|archive-date=2013-12-28}}</ref> 70% of the world's population across 130 countries are receiving iodized salt. In some countries, iodized salt is added to bread.<ref name=Charlton/> Despite this, iodine deficiency has reappeared in some Western countries due to attempts to reduce salt intake.<ref name=Charlton/>

Pregnant and breastfeeding women, who require 66% more daily iodine than non-pregnant women, may still not be getting enough iodine.<ref name=Charlton/><ref>{{cite web |url=https://www.who.int/elena/titles/iodine_pregnancy/en/ |title=Iodine supplementation during pregnancy |author=e-Library of Evidence for Nutrition Actions (eLENA) |year=2014 |publisher=World Health Organization |access-date=5 March 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140306031155/http://www.who.int/elena/titles/iodine_pregnancy/en/ |archive-date=6 March 2014 }}</ref> The World Health Organization recommends a daily intake of 250&nbsp;μg for pregnant and breastfeeding women.<ref name="WHO2007">{{cite web |url=https://www.who.int/nutrition/publications/micronutrients/WHOStatement__IDD_pregnancy.pdf?ua=1 |title=Reaching Optimal Iodine Nutrition in Pregnant and Lactating Women and Young Children |year=2007 |work=Joint Statement by the World Health Organization and United Nations Children's Fund |publisher=World Health Organization |access-date=5 March 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140306014119/http://www.who.int/nutrition/publications/micronutrients/WHOStatement__IDD_pregnancy.pdf?ua=1 |archive-date=6 March 2014 }}</ref> As many women will not achieve this from dietary sources alone, the [[American Thyroid Association]] recommends a 150&nbsp;μg daily supplement by mouth.<ref name=Stagnaro/><ref name="pmid17042677">{{cite journal | vauthors = Becker DV, Braverman LE, Delange F, Dunn JT, Franklyn JA, Hollowell JG, Lamm SH, Mitchell ML, Pearce E, Robbins J, Rovet JF | title = Iodine supplementation for pregnancy and lactation-United States and Canada: recommendations of the American Thyroid Association | journal = Thyroid | volume = 16 | issue = 10 | pages = 949–51 | date = October 2006 | pmid = 17042677 | doi = 10.1089/thy.2006.16.949 | s2cid = 28515565 }}</ref>

==Screening==
[[Screening (medicine)|Screening]] for hypothyroidism is performed in the newborn period in many countries, generally using TSH. This has led to the early identification of many cases and thus the prevention of developmental delay.<ref name="pmid16740880">{{cite journal | vauthors = Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK | title = Update of newborn screening and therapy for congenital hypothyroidism | journal = Pediatrics | volume = 117 | issue = 6 | pages = 2290–303 | date = June 2006 | pmid = 16740880 | doi = 10.1542/peds.2006-0915 | doi-access =  | s2cid = 1068578 }}</ref> It is the most widely used newborn screening test worldwide.<ref>{{cite journal | vauthors = Pollitt RJ | title = Newborn blood spot screening: new opportunities, old problems | journal = Journal of Inherited Metabolic Disease | volume = 32 | issue = 3 | pages = 395–9 | date = June 2009 | pmid = 19412659 | doi = 10.1007/s10545-009-9962-0 | s2cid = 41563580 }}</ref> While TSH-based screening will identify the most common causes, the addition of T<sub>4</sub> testing is required to pick up the rarer central causes of neonatal hypothyroidism.<ref name=Counts/> If T<sub>4</sub> determination is included in the screening done at birth, this will identify cases of congenital hypothyroidism of central origin in 1:16,000 to 1:160,000 children. Considering that these children usually have other [[hypopituitarism|pituitary hormone deficiencies]], early identification of these cases may prevent complications.<ref name=Persani2012/>

In adults, widespread screening of the general population is debated. Some organizations (such as the [[United States Preventive Services Task Force]]) state that evidence is insufficient to support routine 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 = 641–50 | date = May 2015 | pmid = 25798805 | doi = 10.7326/M15-0483 | doi-access =  | s2cid = 262490923 }}</ref> while others (such as the [[American Thyroid Association]]) recommend either intermittent testing above a certain age in all sexes or only in women.<ref name=Garber/> Targeted screening may be appropriate in a number of situations where hypothyroidism is common: other [[autoimmune disease]]s, a strong [[family history]] of thyroid disease, those who have received radioiodine or other radiation therapy to the neck, those who have previously undergone thyroid surgery, those with an abnormal thyroid examination, those with psychiatric disorders, people taking [[amiodarone]] or [[Lithium (medication)|lithium]], and those with a number of health conditions (such as certain heart and skin conditions).<ref name=Garber/> Yearly thyroid function tests are recommended in people with [[Down syndrome]], as they are at higher risk of thyroid disease.<ref name=Malt2013>{{cite journal | vauthors = Malt EA, Dahl RC, Haugsand TM, Ulvestad IH, Emilsen NM, Hansen B, Cardenas YE, Skøld RO, Thorsen AT, Davidsen EM | title = Health and disease in adults with Down syndrome | journal = Tidsskrift for den Norske Laegeforening | volume = 133 | issue = 3 | pages = 290–4 | date = February 2013 | pmid = 23381164 | doi = 10.4045/tidsskr.12.0390 | doi-access = free }}</ref> Guidelines for England and Wales from the National Institute for Health and Care Excellence (NICE) recommend testing for thyroid disease in people with type 1 diabetes and new-onset [[atrial fibrillation]], and suggests testing in those with depression or unexplained anxiety (all ages), in children with abnormal growth, or unexplained change in behavior or school performance.<ref name=NICENG145/> NICE also recommends screening for celiac disease in people with a diagnosis of autoimmune thyroid disease.<ref name=NICENG20>{{cite web |title=Coeliac disease: recognition, assessment and management |url=https://www.nice.org.uk/guidance/ng20 |website=www.nice.org.uk |publisher=National Institute for Health and Care Excellence |access-date=9 March 2021 |date=2 September 2015}}</ref>

==Management==

=== Hormone replacement ===
Hypothyroidism is managed by hormone substitution with a synthetic long-acting form of thyroxine, known as [[levothyroxine]] (<small>L</small>-thyroxine).<ref name="Garber" /><ref name="Khandelwal2012">{{cite journal | vauthors = Khandelwal D, Tandon N | title = Overt and subclinical hypothyroidism: who to treat and how | journal = Drugs | volume = 72 | issue = 1 | pages = 17–33 | date = January 2012 | pmid = 22191793 | doi = 10.2165/11598070-000000000-00000 | s2cid = 207301404 | type = Review }}</ref> In young and otherwise healthy people with overt hypothyroidism, a full replacement dose (adjusted by weight) can be started immediately; in the elderly and people with heart disease a lower starting dose is recommended to prevent over supplementation and risk of complications.<ref name="Garber" /><ref name="Gaitonde2012" /><ref name=NICENG145/> Lower doses may be sufficient in those with subclinical hypothyroidism, while people with central hypothyroidism may require a higher than average dose.<ref name="Garber" />

Blood and TSH levels are monitored to help determine whether the dose is adequate. This is done 4–8 weeks after the start of treatment or a change in levothyroxine dose. Once the adequate replacement dose has been established, the tests can be repeated after 6 and then 12 months, unless there is a change in symptoms.<ref name=Garber/> Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely, such as elevated [[cholesterol]] levels.<ref>{{cite journal |last1=McAninch |first1=Elizabeth A |last2=Rajan |first2=Kumar B |last3=Miller |first3=Corinne H |last4=Bianco |first4=Antonio C |title=Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis |journal=The Journal of Clinical Endocrinology & Metabolism |date=1 December 2018 |volume=103 |issue=12 |pages=4533–4542 |doi=10.1210/jc.2018-01361 |pmid=30124904|pmc=6226605 }}</ref>

In people with central hypothyroidism, TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T<sub>4</sub> level.<ref name=Garber/><ref name=Persani2012/> Levothyroxine is best taken 30–60 minutes before breakfast, or four hours after food,<ref name=Garber/> as certain substances such as food and calcium can inhibit the absorption of levothyroxine.<ref name=Cascorbi2012>{{cite journal | vauthors = Cascorbi I | title = Drug interactions--principles, examples, and clinical consequences | journal = Deutsches Ärzteblatt International | volume = 109 | issue = 33–34 | pages = 546–55; quiz 556 | date = August 2012 | pmid = 23152742 | pmc = 3444856 | doi = 10.3238/arztebl.2012.0546 | type = Review }}</ref> There is no direct way of increasing thyroid hormone secretion by the thyroid gland.<ref name=Khandelwal2012/>

====Liothyronine====
Treatment with [[liothyronine]] (synthetic T<sub>3</sub>) alone has not received enough study to make a recommendation as to its use; due to its shorter half-life it would need to be taken more often than levothyroxine.<ref name=Garber/>

Adding liothyronine to levothyroxine has been suggested as a measure to provide better symptom control, but this has not been confirmed by studies.<ref name=Chakera/><ref name=Khandelwal2012/><ref>{{cite journal | vauthors = Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F, Morreale de Escobar G | title = REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 8 | pages = 4946–54 | date = August 2005 | pmid = 15928247 | doi = 10.1210/jc.2005-0184 | type = Review | doi-access = free | hdl = 10261/24668 | hdl-access = free }}</ref> In 2007, the British Thyroid Association stated that combined T<sub>4</sub> and T<sub>3</sub> therapy carried a higher rate of side effects and no benefit over T<sub>4</sub> alone.<ref name=Khandelwal2012/><ref name=BTA2007>{{cite web|author=British Thyroid Association Executive Committee|title=Armour Thyroid(USP) and combinedthyroxine/tri-iodothyronine as thyroid hormone replacement|url=http://www.british-thyroid-association.org/Guidelines/Docs/Armour_nov_07.pdf|publisher=British Thyroid Association|date=November 2007|access-date=25 December 2013|url-status=dead|archive-url=https://web.archive.org/web/20081203102047/http://www.british-thyroid-association.org/Guidelines/Docs/Armour_nov_07.pdf|archive-date=3 December 2008}}</ref> Similarly, American guidelines discourage combination therapy due to a lack of evidence, although they acknowledge that some people feel better when receiving combination therapy.<ref name=Garber/> Guidelines by [[National Institute for Health and Care Excellence]] (NICE) discourage liothyronine.<ref name=NICENG145/>

People with hypothyroidism who do not feel well despite optimal levothyroxine dosing may request adjunctive treatment with liothyronine. A 2012 guideline from the European Thyroid Association recommends that support should be offered concerning the chronic nature of the disease and that other causes of the symptoms should be excluded. The addition of liothyronine should be regarded as experimental, initially only for a trial period of 3 months, and in a set ratio to the current dose of levothyroxine.<ref name=ETA2012>{{cite journal | vauthors = Wiersinga WM, Duntas L, Fadeyev V, Nygaard B, Vanderpump MP | title = 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism | journal = European Thyroid Journal | volume = 1 | issue = 2 | pages = 55–71 | date = July 2012 | pmid = 24782999 | pmc = 3821467 | doi = 10.1159/000339444 }}</ref> The guideline explicitly aims to enhance the safety of this approach and to counter its indiscriminate use.<ref name=ETA2012/> A 2014 guideline from the American Thyroid Association recommends against the use of liothyronine.<ref name="ATA2014">{{Cite journal |last1=Jonklaas |first1=Jacqueline |last2=Bianco |first2=Antonio C. |last3=Bauer |first3=Andrew J. |last4=Burman |first4=Kenneth D. |last5=Cappola |first5=Anne R. |last6=Celi |first6=Francesco S. |last7=Cooper |first7=David S. |last8=Kim |first8=Brian W. |last9=Peeters |first9=Robin P. |last10=Rosenthal |first10=M. Sara |last11=Sawka |first11=Anna M. |date=12 December 2014 |title=Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement |journal=Thyroid |volume=24 |issue=12 |pages=1670–1751 |doi=10.1089/thy.2014.0028 |issn=1050-7256 |pmc=4267409 |pmid=25266247}}</ref>

====Desiccated animal thyroid====
[[Desiccated thyroid extract]] is an animal-based thyroid gland extract,<ref name=Khandelwal2012/> most commonly from [[pig]]s. It is a combination therapy, containing forms of T<sub>4</sub> and T<sub>3</sub>.<ref name=Khandelwal2012/> It also contains [[calcitonin]] (a hormone produced in the thyroid gland involved in the regulation of calcium levels), T<sub>1</sub> and T<sub>2</sub>; these are not present in synthetic hormone medication.<ref>{{cite web |url=http://www.endocrinesociety.org.au/ESA_Position_Statement_%20Thyroid-Extract.pdf |title=ESA Position Statement on Desiccated Thyroid or Thyroid Extract |vauthors=Ebling PR |year=2011 |publisher=Endocrine Society of Australia |access-date=13 December 2013 |url-status=dead |archive-url=https://web.archive.org/web/20140126012359/http://endocrinesociety.org.au/ESA_Position_Statement_%20Thyroid-Extract.pdf |archive-date=26 January 2014 }}</ref> This extract was once a mainstream hypothyroidism treatment, but has been disregarded since the 1970s and its use is unsupported by evidence;<ref name=Chakera/><ref name=Khandelwal2012/> British Thyroid Association and American professional guidelines discourage its use,<ref name=Garber/><ref name=BTA2007/><ref name="ATA2014" /> as does NICE.<ref name=NICENG145/>

===Subclinical hypothyroidism===
There is no evidence of a benefit from treating subclinical hypothyroidism in those who are not pregnant, and there are potential risks of [[Unnecessary health care|unnecessary overtreatment]].<ref name=BMJ2019>{{cite journal |last1=Bekkering |first1=G E |last2=Agoritsas |first2=T |last3=Lytvyn |first3=L |last4=Heen |first4=A F |last5=Feller |first5=M |last6=Moutzouri |first6=E |last7=Abdulazeem |first7=H |last8=Aertgeerts |first8=B |last9=Beecher |first9=D |last10=Brito |first10=J P |last11=Farhoumand |first11=P D |last12=Singh Ospina |first12=N |last13=Rodondi |first13=N |last14=van Driel |first14=M |last15=Wallace |first15=E |last16=Snel |first16=M |last17=Okwen |first17=P M |last18=Siemieniuk |first18=R |last19=Vandvik |first19=P O |last20=Kuijpers |first20=T |last21=Vermandere |first21=M |title=Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline |journal=BMJ |volume=365 |date=14 May 2019 |pages=l2006 |doi=10.1136/bmj.l2006|pmid=31088853 |doi-access=free }}</ref> Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of [[coronary artery disease]] when the TSH is over 10&nbsp;mIU/L.<ref name=BMJ2019/><ref>{{cite journal | vauthors = Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, Rodondi N | title = Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality | journal = Annals of Internal Medicine | volume = 148 | issue = 11 | pages = 832–45 | date = June 2008 | pmid = 18490668 | doi = 10.7326/0003-4819-148-11-200806030-00225 | type = Meta-analysis | doi-access = free }}</ref> There may be an increased risk for 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> A 2007 review found no benefit of thyroid hormone replacement except for "some parameters of lipid profiles and left ventricular function".<ref name="pmid17636722">{{cite journal | vauthors = Villar HC, Saconato H, Valente O, Atallah AN | title = Thyroid hormone replacement for subclinical hypothyroidism | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD003419 | date = July 2007 | volume = 2009 | pmid = 17636722 | doi = 10.1002/14651858.CD003419.pub2 | pmc = 6610974 }}</ref> There is no association between subclinical hypothyroidism and an increased risk of [[bone fracture]]s,<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 = 2055–65 | date = May 2015 | pmid = 26010634 | pmc = 4729304 | doi = 10.1001/jama.2015.5161 }}</ref> nor is there a link with cognitive decline.<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>

American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism, detectable antibodies against thyroid peroxidase, a history of heart disease, or are at an increased risk for heart disease if the TSH is elevated but below 10&nbsp;mIU/L.<ref name=Garber/> American guidelines further recommend universal treatment (independent of risk factors) in those with TSH levels that are markedly elevated; above 10 mIU/L because of an increased risk of heart failure or death due to cardiovascular disease.<ref name="Garber" /><ref name="Peters 2017" />  NICE recommends that those with a TSH above 10&nbsp;mIU/L should be treated in the same way as overt hypothyroidism. Those with an elevated TSH but below 10&nbsp;mIU/L who have symptoms suggestive of hypothyroidism should have a trial of treatment but intend to stop this if the symptoms persist despite normalization of the TSH.<ref name=NICENG145/>

===Myxedema coma===
[[Myxedema coma]] or severe [[Decompensation|decompensated]] hypothyroidism usually requires admission to the [[intensive care unit|intensive care]], close observation and treatment of abnormalities in breathing, temperature control, blood pressure, and sodium levels. [[Mechanical ventilation]] may be required, as well as [[fluid replacement]], [[Antihypotensive agent|vasopressor agents]], careful rewarming, and [[corticosteroid]]s (for possible [[adrenal insufficiency]] which can occur together with hypothyroidism). Careful correction of low sodium levels may be achieved with [[Hypertonic saline#Hypertonic saline|hypertonic saline solutions]] or [[vasopressin receptor antagonist]]s.<ref name=Klubo/> For rapid treatment of hypothyroidism, levothyroxine or liothyronine may be administered [[Intravenous therapy|intravenously]], particularly if the level of consciousness is too low to be able to safely swallow medication.<ref name=Klubo/> While administration through a [[Nasogastric intubation|nasogastric tube]] is possible, this may be unsafe and is discouraged.<ref name=Klubo/>

===Pregnancy===
In women with known [[Thyroid disease in pregnancy|hypothyroidism who become pregnant]], it is recommended that serum TSH levels are closely monitored. Levothyroxine should be used to keep TSH levels within the normal range for that trimester. The first-trimester normal range is below 2.5&nbsp;mIU/L and the second and third trimesters normal range is below 3.0&nbsp;mIU/L.<ref name=Khandelwal2012/><ref name=Stagnaro/> [[Thyroid function tests#Free thyroxine index|Measurement of free T<sub>4</sub>]] in pregnancy is not recommended due to changes in levels of serum protein binding. Similarly to TSH, the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy.<ref name=Garber/> The levothyroxine dose often needs to be increased after pregnancy is confirmed,<ref name=Garber/><ref name=Gaitonde2012/><ref name=Stagnaro/> although this is based on limited evidence and some recommend that it is not always required; decisions may need to based on TSH levels.<ref name=Wiles2015>{{cite journal | vauthors = Wiles KS, Jarvis S, Nelson-Piercy C | title = Are we overtreating subclinical hypothyroidism in pregnancy? | journal = BMJ | volume = 351 | pages = h4726 | date = October 2015 | pmid = 26459315 | doi = 10.1136/bmj.h4726 | s2cid = 32615623 }}</ref>

Women with anti-TPO antibodies who are trying to become pregnant (naturally or by [[assisted reproductive technology|assisted]] means) may require thyroid hormone supplementation even if the TSH level is normal. This is particularly true if they have had previous miscarriages or have been hypothyroid in the past.<ref name=Garber/> Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage.<ref>{{cite journal | vauthors = Reid SM, Middleton P, Cossich MC, Crowther CA, Bain E | title = Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 5 | pages = CD007752 | date = May 2013 | pmid = 23728666 | doi = 10.1002/14651858.CD007752.pub3 | editor1-last = Reid | editor1-first = Sally M | doi-access = free | pmc = 11664309 }}</ref> The recommendation is stronger in pregnant women with subclinical hypothyroidism (defined as TSH 2.5–10&nbsp;mIU/L) who are anti-TPO positive, in view of the risk of overt hypothyroidism. If a decision is made not to treat, close monitoring of the thyroid function (every 4 weeks in the first 20 weeks of pregnancy) is recommended.<ref name=Garber/><ref name=Stagnaro/> If anti-TPO is not positive, treatment for subclinical hypothyroidism is not currently recommended.<ref name=Stagnaro/> It has been suggested that many of the aforementioned recommendations could lead to unnecessary treatment, in the sense that the TSH cutoff levels may be too restrictive in some ethnic groups; there may be little benefit from treatment of subclinical hypothyroidism in certain cases.<ref name=Wiles2015/> Treatment for subclinical hypothyroidism in pregnancy is not conclusively shown to decrease the incidence of miscarriage.<ref>{{Cite journal |last=Pearce |first=Elizabeth N. |date=1 July 2022 |title=Management of Hypothyroidism and Hypothyroxinemia During Pregnancy |journal=Endocrine Practice |language=English |volume=28 |issue=7 |pages=711–718 |doi=10.1016/j.eprac.2022.05.004 |issn=1530-891X |pmid=35569735}}</ref><ref>{{Cite journal |last1=Provinciatto |first1=Henrique |last2=Moreira |first2=Marcus Vinicius Barbosa |last3=Neves |first3=Gabriel Rezende |last4=De Freitas |first4=Lucas Rezende |last5=Mitsui |first5=Henrique Costa |last6=Zhang |first6=Julio Min Fei |last7=Araujo Júnior |first7=Edward |date=1 June 2024 |title=Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials |journal=Archives of Gynecology and Obstetrics |volume=309 |issue=6 |pages=2387–2393 |doi=10.1007/s00404-024-07512-3 |pmid=38676741 |issn=1432-0711}}</ref><ref>{{Cite journal |last1=Sankoda |first1=Akiko |last2=Suzuki |first2=Hitomi |last3=Imaizumi |first3=Misa |last4=Yoshihara |first4=Ai |last5=Kobayashi |first5=Sakiko |last6=Katai |first6=Miyuki |last7=Hamada |first7=Katsuhiko |last8=Hidaka |first8=Yoh |last9=Yoshihara |first9=Aya |last10=Nakamura |first10=Hannah |last11=Kubota |first11=Sumihisa |last12=Kakita-Kobayashi |first12=Maiko |last13=Iwase |first13=Akira |last14=Sugiyama |first14=Takashi |last15=Ota |first15=Erika |date=18 February 2024 |title=Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials |journal=Thyroid|volume=34 |issue=4 |pages=519–530 |doi=10.1089/thy.2023.0546 |issn=1557-9077 |pmid=38368537}}</ref>

=== Alternative medicine ===
The effectiveness and safety of using Chinese herbal medicines to treat hypothyroidism is not known.<ref>{{cite journal |last1=Ke |first1=Lin-qiu |last2=Hu |first2=Ying |last3=Yang |first3=Kun |last4=Tong |first4=Nanwei |title=Chinese herbal medicines for hypothyroidism |journal=Cochrane Database of Systematic Reviews |date=12 February 2015 |volume=2015 |issue=2 |pages=CD008779 |doi=10.1002/14651858.CD008779.pub2 |pmid=25914906 |pmc=10625441 }}</ref>

==Epidemiology==
Hypothyroidism is the most frequent [[Endocrine disease|endocrine disorder]].<ref name="pmid38019451">{{cite journal | vauthors = Casis O, Echeazarra L, Gallego M | title=Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism | journal= Journal of Physiology and Biochemistry | volume=80 | issue=1 | pages=1–9| year=2024 | doi= 10.1007/s13105-023-01000-z | pmc=10808292 | pmid=38019451}}</ref> Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism.<ref name=WernerIngbar/> In large population-based studies in Western countries with sufficient dietary iodine, 0.3–0.4% of the population have overt hypothyroidism. A larger proportion, 4.3–8.5%, have subclinical hypothyroidism.<ref name=Garber/> Undiagnosed hypothyroidism is estimated to affect about 4–7% of community-derived populations in the US and Europe.<ref>{{cite journal |last1=Gottwald-Hostalek |first1=U |last2=Schulte |first2=B |title=Low awareness and under-diagnosis of hypothyroidism. |journal=Current Medical Research and Opinion |date=January 2022 |volume=38 |issue=1 |pages=59–64 |doi=10.1080/03007995.2021.1997258 |pmid=34698615|s2cid=239888323 |doi-access=free }}</ref> Of people with subclinical hypothyroidism, 80% have a TSH level below the 10&nbsp;mIU/L mark regarded as the threshold for treatment.<ref name=Fatourechi>{{cite journal | vauthors = Fatourechi V | title = Subclinical hypothyroidism: an update for primary care physicians | journal = Mayo Clinic Proceedings | volume = 84 | issue = 1 | pages = 65–71 | year = 2009 | pmid = 19121255 | pmc = 2664572 | doi = 10.4065/84.1.65 | type = Review }}</ref> Children with subclinical hypothyroidism often return to normal thyroid function, and a small proportion develops overt hypothyroidism (as predicted by evolving antibody and TSH levels, the presence of celiac disease, and the presence of a goiter).<ref>{{cite journal | vauthors = Monzani A, Prodam F, Rapa A, Moia S, Agarla V, Bellone S, Bona G | title = Endocrine disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review | journal = European Journal of Endocrinology | volume = 168 | issue = 1 | pages = R1–R11 | date = January 2013 | pmid = 22989466 | doi = 10.1530/EJE-12-0656 | doi-access = free }}</ref>

Women are more likely to develop hypothyroidism than men. In population-based studies, women were seven times more likely than men to have TSH levels above 10 mU/L.<ref name=Garber/> 2–4% of people with subclinical hypothyroidism will progress to overt hypothyroidism each year. The risk is higher in those with antibodies against thyroid peroxidase.<ref name=Garber/><ref name=Fatourechi/> Subclinical hypothyroidism is estimated to affect approximately 2% of children; in adults, subclinical hypothyroidism is more common in the elderly, and in [[White people]].<ref name="Bona2013"/> There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with [[Down syndrome]]<ref name=Counts/><ref name=Malt2013/> and [[Turner syndrome]].<ref name=Counts/>

Very severe hypothyroidism and myxedema coma are rare, with it estimated to occur in 0.22 per million people a year.<ref name=Klubo/> The majority of cases occur in women over 60 years of age, although it may happen in all age groups.<ref name=Klubo/>

Most hypothyroidism is primary in nature. Central/secondary hypothyroidism affects 1:20,000 to 1:80,000 of the population or about one out of every thousand people with hypothyroidism.<ref name=Persani2012/>

==History==
In 1811, [[Bernard Courtois]] discovered iodine was present in [[seaweed]], and iodine intake was linked with [[goiter]] size in 1820 by [[Jean-Francois Coindet]].<ref name=Leung>{{cite journal | vauthors = Leung AM, Braverman LE, Pearce EN | title = History of U.S. iodine fortification and supplementation | journal = Nutrients | volume = 4 | issue = 11 | pages = 1740–6 | date = November 2012 | pmid = 23201844 | pmc = 3509517 | doi = 10.3390/nu4111740 | doi-access = free }}</ref> [[Gaspard Adolphe Chatin]] proposed in 1852 that endemic goiter was the result of not enough iodine intake, and [[Eugen Baumann]] demonstrated iodine in thyroid tissue in 1896.<ref name=Leung/>

The first cases of myxedema were recognized in the mid-19th century (the 1870s), but its connection to the thyroid was not discovered until the 1880s when myxedema was observed in people following the removal of the thyroid gland (thyroidectomy).<ref name=HxofHypoAnnals /> The link was further confirmed in the late 19th century when people and animals who had had their thyroid removed showed improvement in symptoms with transplantation of animal thyroid tissue.<ref name=Chakera/>  The severity of myxedema, and its associated risk of mortality and complications, created interest in discovering effective treatments for hypothyroidism.<ref name=HxofHypoAnnals>{{cite journal | vauthors = McAninch EA, Bianco AC | title = The History and Future of Treatment of Hypothyroidism | journal = Annals of Internal Medicine | volume = 164 | issue = 1 | pages = 50–6 | date = January 2016 | pmid = 26747302 | pmc = 4980994 | doi = 10.7326/M15-1799 }}</ref>  Transplantation of thyroid tissue demonstrated some efficacy, but recurrences of hypothyroidism was relatively common, and sometimes required multiple repeat transplantations of thyroid tissue.<ref name=HxofHypoAnnals />

In 1891, the English physician [[George Redmayne Murray]] introduced subcutaneously injected sheep thyroid extract,<ref>{{cite journal | vauthors = Murray GR | title = Note on the Treatment of Myxoedema by Hypodermic Injections of an Extract of the Thyroid Gland of a Sheep | journal = British Medical Journal | volume = 2 | issue = 1606 | pages = 796–7 | date = October 1891 | pmid = 20753415 | pmc = 2273741 | doi = 10.1136/bmj.2.1606.796 }}</ref> followed shortly after by an oral formulation.<ref name=Chakera/><ref>{{cite journal | vauthors = Fox EL | title = A Case of Myxoedema Treated by Taking Extract of Thyroid by the Mouth | journal = British Medical Journal | volume = 2 | issue = 1661 | pages = 941 | date = October 1892 | pmid = 20753901 | pmc = 2421284 | doi = 10.1136/bmj.2.1661.941 }}</ref>  Purified thyroxine was introduced in 1914 and in the 1930s synthetic thyroxine became available, although desiccated animal thyroid extract remained widely used.  Liothyronine was identified in 1952.<ref name=Chakera/>

Early attempts at titrating therapy for hypothyroidism proved difficult.  After hypothyroidism was found to cause a lower [[basal metabolic rate]], this was used as a marker to guide adjustments in therapy in the early 20th century (around 1915).<ref name=HxofHypoAnnals />  However, a low basal metabolic rate was known to be non-specific, also present in malnutrition.<ref name=HxofHypoAnnals />  The first laboratory test to help assess thyroid status was the serum protein-bound iodine, which came into use around the 1950s.

In 1971, the thyroid stimulating hormone (TSH) radioimmunoassay was developed, which was the most specific marker for assessing thyroid status in patients.<ref name=HxofHypoAnnals />  Many people who were being treated based on basal metabolic rate, minimizing hypothyroid symptoms, or based on serum protein-bound iodine, were found to have excessive thyroid hormone.<ref name=HxofHypoAnnals /> The following year, in 1972, a T<sub>3</sub> radioimmunoassay was developed, and in 1974, a T<sub>4</sub> radioimmunoassay was developed.<ref name=HxofHypoAnnals />

==Other animals==
{{Main|Hypothyroidism in dogs}}
[[File:Hypothyroid Labrador retriever 1.jpg|right|thumb|alt=Photograph of a Labrador Retriever dog with sagging facial skin characteristic of hypothyroidism|Characteristic changes in the facial skin of a [[Labrador Retriever]] with hypothyroidism]]
In veterinary practice, dogs are the species most commonly affected by hypothyroidism. The majority of cases occur as a result of primary hypothyroidism, of which two types are recognized: lymphocytic thyroiditis, which is probably immune-driven and leads to destruction and fibrosis of the thyroid gland, and idiopathic atrophy, which leads to the gradual replacement of the gland by fatty tissue.<ref name=Merck/><ref name=Mooney>{{cite journal | vauthors = Mooney CT | title = Canine hypothyroidism: a review of aetiology and diagnosis | journal = New Zealand Veterinary Journal | volume = 59 | issue = 3 | pages = 105–14 | date = May 2011 | pmid = 21541883 | doi = 10.1080/00480169.2011.563729 | s2cid = 29535272 }}</ref> There is often lethargy, cold intolerance, exercise intolerance, and weight gain. Furthermore, skin changes and fertility problems are seen in dogs with hypothyroidism, as well as many other symptoms.<ref name=Mooney/> The signs of myxedema can be seen in dogs, with prominence of skin folds on the forehead, and cases of myxedema coma are encountered.<ref name=Merck/> The diagnosis can be confirmed by a blood test, as the clinical impression alone may lead to overdiagnosis.<ref name=Merck/><ref name=Mooney/> Lymphocytic thyroiditis is associated with detectable [[Anti-thyroid autoantibodies|antibodies against thyroglobulin]], although they typically become undetectable in advanced disease.<ref name=Mooney/> Treatment is with thyroid hormone replacement.<ref name=Merck/>

Other species that are less commonly affected include cats and horses, as well as other large domestic animals. In cats, hypothyroidism is usually the result of other medical treatments such as surgery or radiation. In young horses, congenital hypothyroidism has been reported predominantly in [[Western Canada]] and has been linked with the mother's diet.<ref name=Merck/>
{{Clear}}

== References ==
{{Reflist}}

== External links ==
* {{cite web |title=Hypothyroidism information for patients|publisher=American Thyroid Association |url=http://www.thyroid.org/hypothyroidism/ }}

{{Medical condition classification and resources
 | DiseasesDB      = 6558
 | ICD10           = {{ICD10|E|03|9|e|00}}
 | ICD9            = {{ICD9|244.9}}
 | MedlinePlus     = 000353
 | eMedicineSubj   = med
 | eMedicineTopic  = 1145
 | MeshID          = D007037
}}

{{Thyroid therapy}}
{{Thyroid disease}}
{{Authority control}}

[[Category:Thyroid disease]]
[[Category:Wikipedia medicine articles ready to translate (full)]]
[[Category:Wikipedia neurology articles ready to translate]]
[[Category:Endocrine diseases]]
[[Category:Autoimmune diseases]]
[[Category:Iodine]]
[[Category:Metabolic disorders]]