Editing Hypothyroidism (section)

==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 />