Thyroid Hormones: Scheme of the thyroid hormone production and regulation on the hypothalamus–pituitary–thyroid axis

Iodine is absorbed from the GI tract and is transferred to the thyroid gland where oxidization and incorporation into tyrosyl residues of thyroglobulin occurs. Tyrosine is further oxidized to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). The combination of 2 molecules of DIT forms thyroxine (T4). Triiodothyronine (T3) is made by the combination of MIT and DIT and by the monodeiodination of T4 in the periphery.

T3 is 4 times more active than the more abundant T4. The half-life of T4 is 5-7 days; the half-life of T3 is only 1 day. Approximately 99% of the circulating thyroid hormone is bound to plasma protein and is metabolized primarily by the liver.

Levels of thyroid hormones in the serum are tightly regulated by the hypothalamic-pituitary-thyroid axis. Thyroid-releasing hormone (TRH) is secreted by the hypothalamus, and stimulates the release of thyroid-stimulating hormone (TSH) from the pituitary gland. Mature TSH reaches the thyroid gland and stimulates thyroid hormone production and release. The main hormone secreted from the thyroid gland is T4, which is converted to T3 by deiodinase in the peripheral organs. Secreted thyroid hormone reaches the hypothalamus and the pituitary, where it inhibits production and secretion of TRH and TSH, thereby establishing the hypothalamic-pituitary-thyroid axis.