Thyroid hormone production and utilization involve several steps (Fig. 29-1). Thyroid gland activity is under the control of thyroid-stimulating hormone (TSH, space or thyrotropin), produced by the anterior pituitary. Pituitary TSH secretion is regulated by space thyrotropin-releasing hormone (TRH, thyroliberin, protirelin) from the hypothalamus. The main space raw material of thyroid hormone is inorganic iodide provided by food. Thyroid hormone synthesis space begins when inorganic iodide is extracted from the blood by the thyroid. Within the thyroid, space in organic iodide is converted to organic iodine, and one iodine atom is incorporated into a space tyrosine nucleus to form monoiodotyrosine. An additional iodine atom is then attached to form space diiodotyrosine. Two diiodotyrosine molecules are combined to form tetraiodothyronine (thyroxine, T4), or one monoiodotyrosine molecule can be combined with one diiodotyrosine molecule to form triiodothyronine (T3). Thyroid hormone is stored in the thyroid acini as thyroglobulin, to be reconstituted and released when needed. Under normal conditions the greater part of thyroid hormone secretion is T4, with only about 7% being T3. In the blood, more than 99% of both T4and T3 is bound to serum proteins. About 80%-85% of T4attaches to T4-binding globulin (TBG), an alpha-1 globulin; about 10%-15% to pre albumin; and about 5% to albumin. Parenthetically, although only a small percentage binds to albumin, there is a large quantity of albumin, so that large changes in serum albumin (usually a decrease) may significantly affect the amount of T4 bound to protein. About 70% of T3 is bound to TBG and most of the remainder to albumin. Protein-bound hormone is metabolically inactive, as though it were in a warehouse for storage. The unbound (“free”) T4and T3 are metabolically active in body cells. Within body cells, particularly the liver, about 80% of daily T3 production takes place by conversion of free T4 to T3. Thyroxine is also converted into a compound known as “reverse T3,” which is not biologically active. Finally, there is a feedback system of control over thyroid hormone production and release. Decreased serum levels of free T4 and T3 stimulate TRH production, whereas increased levels of free T4 and T3 directly inhibit pituitary secretion of TSH as well as inhibit TRH production.

29-1

Fig. 29-1 Iodine and thyroid hormone metabolism.

Certain drugs affect aspects of thyroid hormone production. Perchlorate and cyanate inhibit iodide trapping by the thyroid. The thionalide compounds propylthiouracil (PTU) and methimazole (Tapazole) inhibit thyroid hormone synthesis within the gland from iodine and tyrosine. In addition, PTU inhibits liver conversion of T4 to T3. Iodine in large amounts tends to decrease thyroid vascularity and acinar hyperplasia and to have some inhibitory effect on thyroid hormone release in Graves’ disease. Cortisol has some inhibitory effect on pituitary TSH secretion.