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INTRODUCTION

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The thyroid secretes 2 types of hormones: iodine-containing amino acids (thyroxine and triiodothyronine) and a peptide (calcitonin). Thyroxine and triiodothyronine have broad effects on growth, development, and metabolism. Calcitonin is important in calcium metabolism and is discussed in Chapter 42. This chapter describes the drugs used in the treatment of hypothyroidism and hyperthyroidism.

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THYROID HORMONES

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A. Synthesis and Transport of Thyroid Hormones
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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.

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FIGURE 38–1

Sites of action of some antithyroid drugs. I, iodide ion; I°, elemental iodine. Not shown: radioactive iodine (131I), which destroys the gland through radiation. (Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 12th ed. McGraw-Hill, 2012: Fig. 38–1.)

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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.

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High-Yield Terms to Learn
Cretinism Irreversible mental retardation and dwarfism caused by congenital hypothyroidism
Myxedema Severe hypothyroidism
Goiter Enlargement of the thyroid gland
Graves’ disease Autoimmune disorder that results in hyperthyroidism during the early phase and can progress to hypothyroidism if there is ...

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