## Distinguishing PTU from Methimazole **Key Point:** PTU has a unique dual mechanism of action that methimazole lacks — it inhibits both thyroid peroxidase (TPO) and peripheral conversion of T4 to T3. ### Mechanism Comparison | Feature | PTU | Methimazole | |---------|-----|-------------| | **TPO inhibition** | Yes | Yes | | **Peripheral T4→T3 conversion inhibition** | Yes (unique) | No | | **Onset of action** | 24–36 hours | 24–36 hours | | **Agranulocytosis incidence** | 0.1–0.5% | 0.01–0.1% (lower) | | **Hepatotoxicity** | DILI, cholestasis | Rare | | **Preferred in pregnancy** | 1st trimester | 2nd/3rd trimester | **High-Yield:** The peripheral inhibition of T4→T3 conversion is PTU's distinctive pharmacologic advantage — it provides faster symptomatic relief in severe hyperthyroidism (thyroid storm) because it reduces circulating active T3 immediately, even before new thyroid hormone synthesis is suppressed. **Clinical Pearl:** This is why PTU is preferred in thyroid storm and early severe hyperthyroidism, despite its higher hepatotoxicity risk. The dual action makes it superior for acute symptom control. **Warning:** Do not confuse PTU's advantage with a faster onset — both have similar onset times (~24 hrs). The difference is in the *mechanism breadth*, not speed.
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