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.