22.3 THYROID DISORDERS
Primary function of thyroid gland is to synthesize and store two important hormones—Thyroxin (T4) and Tri-iodotyrosine (T3), later being 3-4 times more metabolically potent than the former.
Only 20% of circulating T3 is directly secreted from thyroid. Rest is produced by de-iodination of T4 in peripheral tissues, mainly liver and kidneys.Physiology: Important steps in thyroidal hormonal synthesis are:
a. Transport of dietary iodine (as iodide) and trapping into thyroid tissue, using an energy dependent sodium-iodide symporter mechanism;
b. Organification (oxidation) of trapped iodide into iodine, catalyzed by thyroidal peroxidase enzyme;
c. Iodination of tyrosine (secreted from thyroid cells as a specific thyroprotein) to produce monoiodotyrosine (MIT) and diiodotyrosine (DIT);
d. Coupling of 2 DIT molecules to form T4 and one DIT and one MIT molecule to form T3;
e. Storage of T4 and T3, as thyroglobulin in thyroid follicles;
f. Liberation of T4 and T3 from thyroglobulin and release in circulation, as and when needed.
Release of these hormones from thyroid is regulated by pituitary TSH, which is inturn controlled by hypothalamic TRH. TRH and consequently TSH production is increased in thyroid deficiency states (positive feedback) and inhibited by hormonal excess (negative feedback).
In circulation, more than 99% of T4 and T3 is bound to various carrier proteins, most important being thyroxin- binding globulin (TBG). Most of the T3 in circulation is produced by peripheral conversion of T4 by the enzyme monodeiodinase. Physiological effects are mediated after their uptake by target cells with specific thyroid hormone receptors.
22.3.1