Thyroid and Parathyroid

Active accumulation of iodide in the thyroid gland is stimulated by TSH, acting via a
specific membrane receptor located in the thyrocyte plasma membrane. This
mechanism is probably through changes in cyclic adenosine monophosphate (cAMP).
Once inside the thyroid cell, the iodide diffuses through the cytoplasm to the apical
membrane. It remains in its free state for a short time before being oxidized by
peroxidase and hydrogen peroxidase. Iodine rapidly links to tyrosine residues present
in abundance in thyroglobulin, a thyroid-specific protein, resulting in the formation of
two separate molecules, monoiodotyrosine (MIT) and diiodotyrosine (DIT). Two
molecules of DIT combine to form tetraiodothyronine, or thyroxine (T4); a molecule
of MIT and DIT combine to form 3,3',5-triiodothyronine (T3) or 3,3'5'triiodothyronine,
reverse T3 (rT3). The coupling steps are catalyzed by peroxidase in
. the presence of H2O2 and also are rate dependent on TSH
When iodide transport is defective or when oxidation to iodine is impaired because of
disease or pharmacologic agents, goiter or hypothyroidism may result. The antithyroid
drugs (propylthiouracil, methimazole, and carbimazole) inhibit the oxidation of iodide
to iodine by competitive inhibition of peroxidase and also may interfere with the
coupling reaction. In high doses iodide also inhibits iodine trapping. It also has an
antithyroid action by inhibiting the proteolysis involved in the release of thyroid
hormone. Potassium iodide tablets often are administered to people exposed to
radiation leaks involving radioactive forms of iodine, such as nuclear accidents,
. because it blocks trapping by the thyroid gland
Storage, Secretion, and Metabolism of Thyroid Hormone
T4 and T3 are bound to thyroglobulin and are stored in the colloid of the thyroid
follicles. Release of the active hormones is by a process of endocytosis. The colloid is
taken up by the follicular cell as discrete packets (endosomes), which then fuse with
lysosomes containing hydroxylases. Hydrolysis results in production of all component
parts, T4, T3, rT3, MIT, and DIT. Through a process of deiodination most of the
iodide is released from MIT and DIT and reused in the follicle. The iodothyronines
are more resistant to this process and are secreted; these steps also are TSH
. dependent
The active thyroid hormones circulate in the plasma attached to plasma proteins,
principally the carrier proteins, thyroid hormone –binding globulin (TBG), thyroid
hormone–binding prealbumin (TBPA), and albumin. About 99.98 percent of thyroid
hormone circulates in the plasma bound to protein, and the remaining 0.02 percent is
unbound and is the free, active physiological fraction. In some conditions TBG may
be increased, usually as a result of estrogen effects of pregnancy or the contraceptive
pill. This results in a higher circulating amount of T4because of increased serum
. binding capacity. In this situation, active free T 4levels remain unaltered
T3 is the more potent of the two thyroid hormones (rT3 is biologically inert), although
its circulating plasma level is much lower than that of T4; the ratio is 10:1 to 20:1. T3
is less tightly bound to protein in the plasma than T4, and so it enters tissues more
readily. T3 is three to four times more active than T4 per unit weight, with a half-life
of about 1 day, compared to about 7 days for T4. Though the thyroid gland produces
some T3 and rT3, it is known that 75 percent of T3 is produced by the extrathyroidal
conversion of T4 to T3 in the peripheral tissues. Almost 85 percent of T4 is converted