Antithyroid Drugs
Key Points
- First-line therapy for pediatric Graves' disease
- Primary agents: Methimazole (MMI) and Propylthiouracil (PTU)
- Goal is to achieve euthyroid state with minimal side effects
- Treatment duration typically 18-24 months before considering discontinuation
- MMI is preferred over PTU due to safety profile
Specific Medications
Methimazole (MMI)
- First-line treatment in pediatrics
- Available strengths: 5mg, 10mg, 20mg tablets
- Once-daily dosing possible
- Better safety profile than PTU
- Pregnancy category D
Propylthiouracil (PTU)
- Second-line agent
- Reserved for special circumstances:
- First trimester pregnancy
- Thyroid storm
- MMI allergy
- Black box warning for liver failure
- Multiple daily doses required
Clinical Pharmacology
Mechanism of Action
- Inhibition of thyroid peroxidase
- Blocks iodine incorporation into thyroglobulin
- Interferes with coupling of iodotyrosines
- Immunomodulatory effects
Pharmacokinetics
- Methimazole:
- Bioavailability: 93%
- Half-life: 4-6 hours
- Duration of action: 24 hours
- Protein binding: 65%
- Propylthiouracil:
- Bioavailability: 75%
- Half-life: 1-2 hours
- Duration of action: 8-12 hours
- Protein binding: 80%
Administration & Dosing
Initial Dosing Guidelines
- Methimazole:
- Starting dose: 0.2-0.5 mg/kg/day
- Maximum initial dose: 30 mg/day
- Divided into 1-2 doses daily
- Propylthiouracil:
- Starting dose: 5-7 mg/kg/day
- Maximum initial dose: 300 mg/day
- Divided into 3 doses daily
Maintenance Therapy
- Titrate based on thyroid function tests
- Typical maintenance doses:
- MMI: 5-10 mg daily
- PTU: 50-150 mg daily
- Consider "Block and Replace" strategy in selected cases
Monitoring Protocol
Initial Phase (First 3 Months)
- Weekly clinical assessment for first month
- CBC with differential every 2 weeks
- Liver function tests monthly
- TFTs every 2-4 weeks
- Monitor for symptoms of toxicity
Maintenance Phase
- Clinical assessment every 3-4 months
- TFTs every 3-4 months
- Annual liver function tests
- Growth and development monitoring
- Assessment for remission indicators
Laboratory Targets
- Free T4: Upper half of normal range
- TSH: May remain suppressed for months
- TRAb levels to assess for remission
Adverse Effects
Minor Side Effects
- Rash (4-6%)
- Arthralgias
- Gastrointestinal upset
- Taste alterations
Major Side Effects
- Agranulocytosis (0.2-0.5%)
- Usually occurs in first 90 days
- Requires immediate drug discontinuation
- Hepatotoxicity
- More common with PTU
- Can be fulminant
- Vasculitis (PTU)
- ANCA-positive vasculitis
Special Considerations
Pregnancy and Breastfeeding
- PTU preferred in first trimester
- Switch to MMI after first trimester
- Both compatible with breastfeeding
- Regular monitoring of infant thyroid function
Treatment Duration
- Optimal duration: 18-24 months
- Factors favoring remission:
- Mild disease at diagnosis
- Good compliance
- Declining TRAb levels
- Normal thyroid size
Indications for Definitive Therapy
- Failed medical therapy
- Major side effects
- Poor compliance
- Patient preference
Further Reading
