Antithyroid Drugs
Methimazole and PTU both block thyroid hormone synthesis, but only one is safe in the first trimester — and picking wrong can cause birth defects.
Core Concept
Antithyroid drugs treat hyperthyroidism (most commonly Graves' disease) by inhibiting thyroid peroxidase, the enzyme that organifies iodine and couples iodotyrosines into T3 and T4. Methimazole is the preferred first-line agent because of once-daily dosing and a lower side-effect profile. PTU (propylthiouracil) has one unique advantage: it also blocks peripheral conversion of T4 to T3, making it the drug of choice in thyroid storm and during the first trimester of pregnancy (methimazole is teratogenic — associated with aplasia cutis and choanal atresia). After the first trimester, patients are typically switched back to methimazole because PTU carries a higher risk of fatal hepatotoxicity. Both drugs take 3–8 weeks to lower hormone levels because they block new synthesis but do not destroy stored hormone. The most dangerous shared adverse effect is agranulocytosis — a sudden, severe drop in white blood cells. Any patient presenting with fever, sore throat, or mouth sores while on either drug needs an immediate CBC with differential. The drug is held until results confirm WBC recovery. Routine monitoring includes thyroid function tests (TSH, free T4) every 4–6 weeks during dose titration and periodic liver function tests, especially with PTU.
Watch Out For
Don't confuse antithyroid drugs (block synthesis of new hormone) with radioactive iodine (destroys thyroid tissue) — antithyroid drugs are reversible. Students mix up which drug is first-trimester safe: PTU in trimester one, methimazole the rest of the time. Agranulocytosis is not the same as mild leukopenia — it's an emergency requiring immediate drug discontinuation, not dose adjustment.
Clinical Pearl
Sore throat + fever on methimazole or PTU = agranulocytosis until proven otherwise. Stop the drug and draw a CBC — don't wait for the next scheduled lab.
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