Thyroid gland: Anatomy and physiology.

The thyroid gland is the first endocrine gland to develop in humans. Differentiated follicular cells (thyrocytes) are polarized cells with a basolateral and an apical surface. This polarity is functionally paramount, as iodine uptake occurs at the basolateral side, while thyroid hormone secretion occurs at the apical side. The thyroid gland is a highly vascularized organ located anteriorly in the neck between the C5 and T1 vertebrae, and it is divided into two lobes (right and left) and one connecting isthmus. The thyroid hormone synthesis can be subdivided into three main steps: (i) iodide uptake; (ii) iodide oxidation and organification; (iii) secretion of thyroid hormones. Active iodide uptake in thyrocytes is the first step in the biosynthesis of the iodine-containing thyroid hormones. Approximately 150 mg iodide are required by the thyroid gland for its daily activity. The sodium/iodide symporter (NIS), which is located in the basolateral membrane of the follicular cell, entraps iodide from the circulation into cytoplasm. Upon its entry into the cytoplasm of the polarized thyrocyte, iodide moves apically, where it is oxidized and covalently bound to thyroglobulin (Tg). This step requires TPO and H2O2. TPO acts as an H2O2 donor and oxidizes iodide. The resulting compound maybe I+ or OI− (hypoiodite); both are capable of interacting with Tg. Iodination of Tg results in monoiodotyrosine (MIT) and diiodotyrosine (DIT). When a MIT (donor) is coupled to a neighboring DIT (acceptor), 3,5,3′-triiodothyronine (T3) is generated, whereas when a DIT (donor) is coupled to another neighboring DIT (acceptor), 3,5,3′,5′-tetraiodothyronine or thyroxine (T4) is generated. Thyronamines are molecules with a chemical structure similar to thyroid hormones, with biological agonist or antagonist action. Thyroid hormones biosynthesis and metabolism is regulated by at least three factors: TSH-induced stimulation, iodine availability, and deiodinases activity.