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Thyroid hormone
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== Production == === Central === === Peripheral === T4 is a [[prohormone]] and a reservoir for the biologically active T3. T<sub>4</sub> is converted to T3 by deiodinase enzymes. There are three types of deiodinase enzymes: * '''Type 1 (D1)''' deiodinates T4 to the biologically active T3 as well as the hormonally inactive and possibly inhibitory rT3. Breaks down rT3 into T2. Encoded by ''DIO1'' gene''.'' In humans, it is found in liver, kidney, thyroid, and pituitary.<ref name=":0">{{Cite journal | last =Medici | first = Marco | date = March 2017 | title = Genetics of thyroid function|url=https://www.sciencedirect.com/science/article/abs/pii/S1521690X17300301|journal=Best Practice & Research Clinical Endocrinology & Metabolism|volume=31|pages=129-142|via=}}</ref> * '''Type 2 (D2)''' converts T4 into T3, and breaks down rT3 into T2. Encoded by ''DIO2'' gene''.'' In humans, it is found in skeletal muscle, central nervous system, pituitary, thyroid, heart, and brown adipose tissue.<ref name=":0" /> * '''Type 3 (D3)''' produces rT3 from T4, and breaks down T3 into T2. Encoded by ''DIO3'' gene''.'' In humans, it has been found in the central nervous system and placenta in adults and in many additional tissues in the fetus.<ref name=":0" /> === Genetic factors === It is estimated that 40–65% of the inter-individual variation in serum TSH and FT4 levels is determined by genetic factors.<ref name=":0" /> Genetic factors may influence individual variation in the ability to convert T4 to T3. Several SNPs of the ''[[DIO1]]'' gene'','' which encodes for the D1 enzyme, and ''[[DIO2]]'' gene, which encodes for the D2 enzyme, have been studied. ==== D1O1 ==== '''rs2235544''': The homozygous mutant allele (A;A) is associated decreased deiodinase function, resulting in a lower FT3/FT4 ratio, lower T3 and high T4 compared to wild type.<ref name=":0" /><ref>{{Cite journal | last =Panicker | first = V | date = August 2008 | title = A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine|url=https://www.ncbi.nlm.nih.gov/pubmed/18492748?dopt=Abstract|journal=Journal of Clinical Endocrinology Metabolism|volume=93|pages=3075-81|via=}}</ref> ==== D2O2 ==== '''rs225014''': Also known as [[Thr92Ala]], represents a variant in the deiodinase, iodothyronine, type II DIO2 gene on chromosome 14. A study of 102 patients pre- and post- total thyroidectomy showed that after receiving T4-only hormone replacement, 34% of patients had lower reduced Free T3 levels (FT3) than they had pre-surgery. Those with [[mutant]] alleles of [[Thr92Ala]] had lower levels of Free T3 hormone than [[wild type]] (Thr/Thr) / (T;T) patients. The percentage of reduced post-surgery FT3 levels was directly correlated with the presence and severity of the polymorphism: 58.3% in homozygous (Ala/Ala) / (C;C) patients vs 36.5% in heterozygous (Thr/Ala) / (T;C) subjects.<ref>{{Cite journal | last =Castagna | first = Maria | date = May 2017 | title = DIO2 Thr92Ala Reduces Deiodinase-2 Activity and Serum-T3 Levels in Thyroid-Deficient Patients|url=https://academic.oup.com/jcem/article/102/5/1623/2966904|journal=The Journal of Clinical Endocrinology & Metabolism|volume=102|pages=1623–1630|via=}}</ref> '''rs12885300:''' In a study of patients after thyroidectomy, patients with appeared to have an "have an altered set point of the hypothalamus-pituitary-thyroid axis" with a weaker negative feedback of FT4 on TSH in patients with homozygous mutant alleles (C;C).<ref>{{Cite journal | last =Hoftijzer | first=HC | date = September 2011 | title = The type 2 deiodinase ORFa-Gly3Asp polymorphism (rs12885300) influences the set point of the hypothalamus-pituitary-thyroid axis in patients treated for differentiated thyroid carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/21715540?dopt=Abstract|journal=Journal of Clinical Endocrinology and Metabolism|volume=96|pages=1527-33|via=}}</ref>
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