**2. Physiology of thyroid hormones**

The level of thyroid hormones in the circulation is controlled by the hypothalamic-pituitary-thyroid axis (HPT axis) [13]. Thyrotropin-releasing hormone (TRH) is produced and secreted from the medial neurons of the paraventricular nucleus (PVN) of the hypothalamus. TRH in turn regulates both production and secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary cells. Next, TSH through action on its receptor (TSHR) located on the follicular cells of the thyroid gland stimulates synthesis and secretion of the thyroid hormones. There are two types of thyroid hormones, 3,5,30,50-L-tetraiodothyronine (T4), the prohormone, and 3,5,30-L-triiodothyronine (T3), the active hormone [14].

Thyroid hormones exert negative feedback effect on TRH and TSH and thus inhibit own synthesis and secretion.

Thus the HPT axis maintains a balanced relationship between the circulating thyroid hormones and their regulators like TSH and TRH. The set point for adequate functioning of the HPT axis is partly determined by genetic factors; there is an estimated genetic variation of 45–65% [13, 14].
