Chapter 38: Thyroid & Antithyroid Drugs

INTRODUCTION

THYROID HORMONES

A. Synthesis and Transport of Thyroid Hormones

The thyroid secretes 2 iodine-containing hormones: thyroxine (T₄) and triiodothyronine (T₃). The iodine necessary for the synthesis of these molecules comes from food or iodide supplements. Iodide ion is actively taken up by and highly concentrated in the thyroid gland, where it is converted to elemental iodine by thyroidal peroxidase (Figure 38–1). The protein thyroglobulin serves as a scaffold for thyroid hormone synthesis. Tyrosine residues in thyroglobulin are iodinated to form monoiodotyrosine (MIT) or diiodotyrosine (DIT) in a process known as iodine organification. Within thyroglobulin, 2 molecules of DIT combine to form T₄, while 1 molecule each of MIT and DIT combine to form T₃. Proteolysis of thyroglobulin liberates the T₄ and T₃, which are then released from the thyroid. After release from the gland, T₄ and T₃ are transported in the blood by thyroxine-binding globulin, a protein synthesized in the liver.

Thyroid function is controlled by the pituitary through the release of thyrotropin (thyroid-stimulating hormone [TSH]) (see Figure 37–1) and by the availability of iodide. Thyrotropin stimulates the uptake of iodide as well as synthesis and release of thyroid hormone. It also has a growth-promoting effect that causes thyroid cell hyperplasia and an enlarged gland (goiter). High levels of thyroid hormones inhibit the release of TSH, providing an effective negative feedback control mechanism. In Graves’ disease, an autoimmune disorder, B lymphocytes produce an antibody that activates the TSH receptor and can cause a syndrome of hyperthyroidism called thyrotoxicosis. Because these lymphocytes are not susceptible to negative feedback, patients with Graves’ disease can have very high blood concentrations of thyroid hormone at the same time that their blood concentrations of TSH are very low.