Hyperthyroidism: Thionamides and Storm Management
Drug selection rules, adverse effects, and thyroid storm protocol
Methimazole vs. Propylthiouracil
Preferred Agent
Methimazole
- Bioavailability ~93%; once-daily dosing
- 10× more potent than propylthiouracil
- Blocks thyroid peroxidase only
- Hepatotoxicity: cholestatic, mild, reversible
- Teratogenic weeks 6–10 (embryopathy)
- Use: all non-pregnant adults; switch to at 16 weeks
Special Situations
Propylthiouracil
- Bioavailability 50–75%; three times daily dosing
- Blocks thyroid peroxidase AND type 1 deiodinase
- Lowers T3 40% faster than methimazole
- Hepatotoxicity: fulminant (FDA black box)
- Lower placental transfer per milligram
- Use: 1st trimester pregnancy; thyroid storm
Shared Adverse Effects — Both Thionamides
Class Effect
Agranulocytosis
- Incidence 0.1–0.5%; typically within 90 days
- Presents as fever and sore throat — stop drug immediately
- Idiosyncratic — routine blood counts do not prevent
- Do not rechallenge with the other thionamide
- Granulocyte colony-stimulating factor accelerates recovery
Non-Negotiable Education
Patient Instruction
- Stop the drug immediately if fever or sore throat occurs
- Go to emergency department — do not wait for appointment
- Do not self-treat with antibiotics
- Vasculitis (antineutrophil cytoplasmic antibody): propylthiouracil only, up to 4%
Thyroid Storm: Mandatory Treatment Sequence
Step 1
Propylthiouracil 500–1000 mg load, then 200–250 mg q4h
→
Step 2
Propranolol IV or oral — adrenergic control + T3 reduction
→
Step 3
Hydrocortisone 100 mg IV q8h — secretion inhibition + adrenal coverage
→
Step 4 (≥1 hr after Step 1)
Iodide (Lugol’s or saturated solution of potassium iodide) — blocks hormone release
Iodide Rule + Salicylate Warning
Iodide must follow thionamide by at least 1 hour — giving iodide first can worsen thyrotoxicosis by providing substrate before Wolff-Chaikoff blockade is established. • Avoid salicylates in thyroid storm — aspirin displaces T4 and T3 from binding proteins, acutely raising free hormone at a critical moment. Use acetaminophen only.