Thyroid hormone synthesis requires thyroid peroxidase (TPO) for organification of iodide and coupling of iodotyrosines. Propylthiouracil (PTU) blocks TPO. An additional unique advantage of PTU over methimazole in thyroid storm is:

• A PTU has faster onset of action in blocking TPO because it is more lipid-soluble than methimazole
• B PTU inhibits peripheral conversion of T4 to T3 by blocking type 1 deiodinase, providing faster reduction of active thyroid hormone ✓
• C PTU does not cross the placenta and is safe throughout pregnancy
• D PTU activates thyroid hormone receptor beta isoform inhibitory feedback in the pituitary

Explanation

Both PTU and methimazole block TPO, inhibiting thyroid hormone synthesis. However, PTU uniquely inhibits type 1 deiodinase (5'-deiodinase) in peripheral tissues, blocking the conversion of the relatively inactive T4 to the highly active T3. In thyroid storm, where T3 toxicity is acute and life-threatening, this additional peripheral action makes PTU the preferred agent because it provides faster clinical benefit by reducing active T3 without waiting for stored hormone to be depleted. Methimazole lacks this peripheral deiodinase-inhibiting property.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.