Thioamides Methimazole and propylthiouracil (PTU) are small sulfur-containing thioamides that inhibit thyroid hormone synthesis by blocking peroxidase-catalyzed reactions, iodination of the tyrosine residues of thyroglobulin, and coupling of DIT and MIT (Figure 38–1). Propylthiouracil and, to a much lesser extent, methimazole inhibit peripheral conversion of T4 to T3. Because the thioamides do not inhibit the release of preformed thyroid hormone, their onset of activity is usually slow, often requiring 3–4 wk for full effect. The thioamides can be used by the oral route and are effective in young patients with small glands and mild disease. Methimazole is generally preferred because it can be administered once per day. However, PTU is preferred in pregnancy because it is less likely than methimazole to cross the placenta and enter breast milk. Toxic effects include skin rash (common) and severe reactions (rare) such as vasculitis, agranulocytosis, hypoprothrombinemia, and liver dysfunction. These effects are usually reversible.

Iodide Salts and Iodine Iodide salts inhibit iodination of tyrosine and thyroid hormone release (Figure 38–1); these salts also decrease the size and vascularity of the hyperplastic thyroid gland. Because iodide salts inhibit release as well as synthesis of the hormones, their onset of action occurs rapidly, within 2–7 d. However, the effects are transient; the thyroid gland "escapes" from the iodide block after several weeks of treatment. Iodide salts are used in the management of thyroid storm and to prepare patients for surgical resection of a hyperactive thyroid. The usual forms of this drug are Lugol's solution (iodine and potassium iodide) and saturated solution of potassium iodide. Adverse effects include rash, drug fever, metallic taste, bleeding disorders, and, rarely, anaphylactic reactions.

Radioactive Iodine Radioactive iodine (131I) is taken up and concentrated in the thyroid gland so avidly that a dose large enough to severely damage the gland can be given without endangering other tissues. Unlike the thioamides and iodide salts, an effective dose of 131I can produce a permanent cure of thyrotoxicosis without surgery. 131I should not be used in pregnant.

Anion Inhibitors Anions such as thiocyanate (SCN–) and perchlorate (ClO4–) block the uptake of iodide by the thyroid gland through competitive inhibition of the iodide transporter. Their effectiveness is unpredictable and ClO4– can cause aplastic anemia, so these drugs are rarely used clinically.

Other Drugs An important class of drugs for the treatment of thyrotoxicosis is the blockers. These agents are particularly useful in controlling the tachycardia and other cardiac abnormalities of severe thyrotoxicosis. Propranolol also inhibits the peripheral conversion of T4 to T3.