Which antithyroid drug acts primarily by inhibiting thyroid peroxidase and blocking organification of iodine?

Explanation

## Mechanism of Antithyroid Drugs **Key Point:** Propylthiouracil (PTU) is a thionamide that inhibits thyroid peroxidase (TPO), the enzyme responsible for iodination and coupling of tyrosine residues to form T3 and T4. It also has a secondary benefit of inhibiting peripheral conversion of T4 to T3. ### Comparison of Antithyroid Agents | Drug | Primary Mechanism | Secondary Effects | Clinical Use | | --- | --- | --- | --- | | **PTU** | TPO inhibition + organification block | Inhibits T4→T3 conversion | First-line in pregnancy (1st trimester), agranulocytosis risk | | **Methimazole** | TPO inhibition + organification block | None | Preferred maintenance therapy, lower hepatotoxicity | | **Iodine (Lugol's)** | Inhibits thyroid hormone release | Decreases gland vascularity | Acute thyroid storm, preoperative preparation | | **Propranolol** | None (symptom relief only) | β-blockade | Tachycardia, tremor, anxiety relief | | **Sodium perchlorate** | Inhibits iodine uptake | Rare use | Not standard (high nephrotoxicity) | **High-Yield:** PTU's dual mechanism (organification block + T4→T3 inhibition) makes it superior in thyroid storm and pregnancy, despite higher hepatotoxicity risk compared to methimazole. **Clinical Pearl:** Methimazole is preferred for maintenance therapy in non-pregnant patients due to better hepatic safety profile and longer half-life (allowing once-daily dosing), but PTU is mandatory in the first trimester of pregnancy because methimazole carries a rare risk of methimazole embryopathy (methimazole-induced cutis aplasia). **Mnemonic:** **PITO** — PTU Inhibits both Thyroid perOxidase and T4→T3 conversion.