THYROID HORMONE SYNTHESIS
The major synthetic steps regulated by TSH are transport of iodide, organification, coupling, Tg synthesis, and endocytotic secretion. Under the stimulation of TSH, the thyroid cells remove iodide from the capillary network at the base of the cell (see Fig. 30-2) and move the iodide to the apex of the cell, where it is joined with molecules of tyrosine to make mostly T4 and some T3. T4 and T3 are stored in colloid within the follicles of the gland. They are then released together, or some T4 is further deiodinated to T3 before release (see Fig. 30-2). These two steps are also under the influence of TSH or other proteins that bind to the TSH receptor. Mutations of this TSH receptor are continuously activated in some toxic adenomas and multinodular goiters.9 A small but measurable amount of non–TSH-dependent T4 secretion also occurs normally.
ORGANIFICATION
Iodide ions transported into the thyroid cell are oxidized before being used for iodinating tyrosyl residues present in the Tg molecules. This process, called organification, takes place at the apex of the cell (see Fig. 30-2) and requires the enzyme thyroid peroxidase (TPO). The decrease in peroxidase activity and organification that follows iodine excess, known as the Wolff-Chaikoff effect, may protect against hyperthyroidism. The effect is transient, and “escape” occurs within several days. Failure to escape from the Wolff-Chaikoff effect is common in certain diseased glands; therefore, the reduction in organification due to iodine excess is perpetuated, leading to hypothyroidism1 (see Chap. 37). The activity of TPO may be deficient on a congenital basis and is reduced by antimicrosomal antibodies directed against it (see Chap. 46 and Chap. 197) or with administration of thiourea drugs, such as propylthiouracil (PTU), which is commonly used to treat hyperthyroidism (see Chap. 42).
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