Which of the following antithyroid drugs acts primarily by inhibiting thyroid peroxidase and blocking the incorporation of iodine into thyroid hormones?

Explanation

## Mechanism of Propylthiouracil (PTU) **Key Point:** Propylthiouracil is a thionamide antithyroid drug that inhibits thyroid peroxidase (TPO), the enzyme responsible for iodination and coupling of tyrosine residues to form T3 and T4. ### Dual Action of PTU Unlike methimazole, PTU has TWO mechanisms: 1. **Inhibits TPO** — blocks organification of iodine (primary effect) 2. **Inhibits peripheral conversion** of T4 → T3 via 5'-deiodinase inhibition (secondary effect) ### Comparison of Antithyroid Drugs | Drug | Mechanism | Onset | Preferred Use | |------|-----------|-------|---------------| | **Propylthiouracil (PTU)** | TPO inhibition + T4→T3 conversion block | 1–2 weeks | Pregnancy (1st trimester), thyroid storm | | **Methimazole** | TPO inhibition only | 1–2 weeks | Maintenance therapy, non-pregnant | | **Iodine (Lugol's/KI)** | Inhibits hormone release, decreases vascularity | Hours | Acute thyroid storm, pre-operative | | **Propranolol** | β-blocker; no effect on hormone synthesis | Minutes | Symptom relief only (tachycardia, tremor) | | **Lithium** | Inhibits hormone release, decreases iodine uptake | Days | Adjunctive in thyroid storm | **High-Yield:** PTU is preferred in **first trimester pregnancy** because methimazole is associated with methimazole embryopathy (methimazole-induced aplasia cutis). After first trimester, methimazole is preferred due to lower hepatotoxicity risk. **Clinical Pearl:** PTU's ability to block peripheral T4→T3 conversion makes it uniquely useful in thyroid storm, where rapid reduction of active T3 is critical. [cite:KD Tripathi 8e Ch 42]