A 32-year-old woman with Graves' disease presents with thyroid storm. She is severely symptomatic with a heart rate of 140/min, fever, and altered mental status. Which drug should be administered first to rapidly block thyroid hormone synthesis and release?

Explanation

## First-Line Drug in Thyroid Storm **Key Point:** Propylthiouracil (PTU) is the drug of choice in thyroid storm and acute severe hyperthyroidism because it has dual action: blocks thyroid peroxidase (TPO) enzyme AND inhibits peripheral conversion of T₄ to T₃ (the more active form). ## Why PTU Over Methimazole in Acute Settings | Feature | PTU | Methimazole | |---------|-----|-------------| | **Blocks TPO** | Yes | Yes | | **Blocks T₄→T₃ conversion** | Yes (at high doses) | No | | **Onset of action** | Faster (1–2 weeks) | Slower (2–4 weeks) | | **Use in thyroid storm** | First-line | Not preferred | | **Use in pregnancy** | First trimester | Teratogenic (methimazole embryopathy) | **High-Yield:** In thyroid storm, PTU reduces circulating T₃ levels more rapidly than methimazole because it blocks both synthesis AND peripheral conversion. ## Management Sequence in Thyroid Storm 1. **PTU** — blocks new hormone synthesis + peripheral conversion 2. **Iodine solution** (Lugol's or SSKI) — given 1 hour AFTER PTU; blocks hormone release from gland 3. **Beta-blocker** (propranolol) — controls adrenergic symptoms; also has minor effect on T₄→T₃ conversion 4. **Supportive care** — cooling, hydration, treatment of precipitant **Clinical Pearl:** Iodine must be given AFTER PTU (not before) because iodine alone can increase hormone synthesis and worsen the crisis if TPO is not already blocked. **Warning:** Methimazole is NOT suitable in thyroid storm because it does not block peripheral conversion of T₄ to T₃, and onset is slower. [cite:Harrison 21e Ch 397]