What is the mechanism of action of PROPYLTHIOURACIL (PTU)?

Correct answer: A. Inhibits thyroid peroxidase AND blocks peripheral conversion of T4 to T3

• A. CORRECT. PROPYLTHIOURACIL is a thionamide with a DUAL action: it inhibits THYROID PEROXIDASE, blocking the oxidation and organification of iodide and the coupling of iodotyrosines within the follicle, AND it inhibits peripheral 5'-DEIODINASE, preventing conversion of T4 to the more active T3. That second peripheral action is unique among the thionamides and is why PTU is preferred in thyroid storm.
• B. No antithyroid agent works by increasing receptor sensitivity — that would worsen hyperthyroidism.
• C. Blocking iodide UPTAKE at the symporter is the action of competitive anions such as perchlorate and thiocyanate, not of PTU.
• D. Thionamides do not trigger hormone release. Note that they do NOT affect ALREADY STORED colloid hormone either, which is why clinical improvement takes several weeks.

Note: PTU versus METHIMAZOLE: methimazole is more potent, has a longer half-life and is first-line for most patients. PTU is reserved for the FIRST TRIMESTER of pregnancy (methimazole is teratogenic — aplasia cutis, choanal atresia) and for THYROID STORM. PTU carries a black-box warning for HEPATOTOXICITY. Both can cause AGRANULOCYTOSIS — a sore throat, oral ulceration or fever in a patient on either drug demands an urgent white cell count.