Thyroid and Antithyroid Drugs

Thyroid and Antithyroid Drugs

Three hormones, thyroxine (3,5,3’ ,5’ -tetraiodothy-ronine, or T₄), triiodothyronine (3,5,3’ -triiodothyronine, or T₃), and calcitonin  are secreted by the thyroid gland. The hormones T₄ and T₃ are iodine-containing amino acid derivatives and are unique in that they have no discrete target tissue. Every tissue in the body is affected in some way by thyroid hormones, and almost all cells appear to require constant optimal amounts for normal operation.

Thyroid hormones exert a wide variety of physio-logical actions through genomic and nongenomic mech-anisms and influence the metabolism of proteins, car-bohydrates, and lipids; cell morphology; membrane transport; ion homeostasis; oxygen consumption; heat production; and so on. Relatively constant circulating concentrations of T₄ and T₃ are required for normal growth and development and the proper functioning of the neural, reproductive, cardiovascular, gastrointesti-nal, and hematopoietic systems. Unlike most other hor-mones, whose circulating concentrations vary widely in response to external and internal stimuli, the circulating concentrations of thyroid hormones are usually held relatively constant over time.

In health, two negative feedback control systems op-erate to maintain circulating thyroid hormone levels. The first, the hypothalamic–pituitary-thyroid axis (HPTA), acts to regulate the concentration of thyroid hormones in the blood by controlling their synthesis and secretion by the thyroid gland. The second negative feedback control system is the thyroid autoregulatory system. It is intrinsic to the thyroid gland and acts to ensure that an adequate supply of iodide is extracted from the blood and made available for thyroid hormone synthesis de-spite variations in dietary iodine intake.

Worldwide, the most common thyroid disorder is hy-pothyroidism resulting from dietary iodine deficiency. In iodine-replete areas of the world, most thyroid disor-ders are the result of autoimmune disease. The symp-toms manifested in hypothyroid and hyperthyroid states are largely independent of any underlying disor-der of the thyroid gland itself; they are a function of the degree of hormone deficiency or excess.

A second dietary trace element, selenium, is also es-sential for normal thyroid hormone metabolism. Selenium in the form of selenocysteine is a required component for three enzymes that remove iodide from thyroid hormones. Deiodination is the major metabolic pathway by which T₄ and T₃ are cleared from the sys-tem. After secretion by the thyroid gland, T₄ may be deiodinated to yield either T₃ or the physiologically in-active reverse T₃ (3,3’ ,5’ -triiodothyronine, or rT₃). T₃ and rT₃ are further deiodinated to form less active metabolites. Selenium, like iodine, is deficient in many areas of the world.