thionamide

Thionamides are a class of antithyroid drugs used to treat hyperthyroidism. The principal agents include methimazole, carbimazole, and propylthiouracil (PTU). They act by inhibiting thyroid hormone synthesis rather than releasing stored hormone.

Mechanism of action: Thionamides inhibit thyroid peroxidase, blocking iodination of tyrosine residues in thyroglobulin and the coupling of MIT and DIT, which reduces production of thyroid hormones T3 and T4. Propylthiouracil also inhibits peripheral conversion of T4 to T3 in liver and peripheral tissues, providing an additional mechanism of effect.

Clinical use: They are commonly used as first-line therapy for various forms of hyperthyroidism and to prepare patients for definitive treatment such as surgery or radioactive iodine. PTU is preferred in the first trimester of pregnancy due to teratogenic concerns with methimazole, while methimazole or carbimazole is generally used in later pregnancy. In thyroid storm, PTU may be employed for its rapid action. Dose and duration are tailored to achieve euthyroidism, with full therapeutic effect often developing over weeks.

Adverse effects and safety: The most serious risk is agranulocytosis, though it is uncommon. Other adverse effects include rash, vasculitis, and hypersensitivity reactions. Hepatotoxicity is a notable concern with PTU and, less commonly, with methimazole or carbimazole. Overtreatment can cause iatrogenic hypothyroidism. Pregnancy and lactation require special considerations: methimazole is avoided in the first trimester due to fetal anomalies, while PTU is preferred initially; both drugs can be present in breast milk at low levels.

Monitoring: Baseline and periodic thyroid function tests, along with complete blood count and liver function tests when indicated. Patients should report fever, sore throat, or malaise promptly due to risk of agranulocytosis.