What is the recommended dose of Propylthiouracil (PTU) for hyperthyroidism treatment?

Propylthiouracil (PTU) Dosing for Hyperthyroidism Treatment

The recommended initial dose of propylthiouracil (PTU) for adults with hyperthyroidism is 300 mg daily, divided into three equal doses of 100 mg taken at approximately 8-hour intervals. 1

Adult Dosing Guidelines

Initial Dosing

• Standard initial dose: 300 mg daily (divided into 3 equal doses)
• For severe hyperthyroidism or very large goiters: 400 mg daily
• In exceptional cases: 600-900 mg daily may be required initially

Maintenance Dosing

• Usual maintenance dose: 100-150 mg daily (divided into 3 equal doses)
• Dose should be adjusted based on clinical response and thyroid function tests

Monitoring and Dose Adjustment

• Measure Free T4 (FT4) or Free T4 Index (FTI) every 2-4 weeks initially 2
• Goal: Maintain FT4 or FTI in the high-normal range using the lowest possible dose
• Monitor for signs of overtreatment (suppressed TSH) or undertreatment (elevated FT4)
• Once stable, monitoring can be less frequent (every 3-6 months)

Special Populations

Pregnancy Considerations

• PTU is preferred in the first trimester of pregnancy 2
• Consider switching to methimazole in the second and third trimesters due to risk of PTU-associated hepatotoxicity 2
• Women treated with PTU can breastfeed safely 2

Elderly Patients

• Dose selection should be cautious in elderly patients
• Start at lower doses due to potentially decreased hepatic, renal, or cardiac function
• Consider comorbidities and drug interactions 1

Pediatric Patients

• Generally not recommended for pediatric use except in rare instances
• If necessary in children ≥6 years: start at 50 mg daily with careful upward titration
• Monitor TSH and free T4 levels closely 1

Important Considerations and Potential Side Effects

Monitoring for Side Effects

• Agranulocytosis: Usually presents with sore throat and fever
  • If these symptoms develop, obtain a complete blood count and discontinue PTU
• Hepatotoxicity: More common with PTU than methimazole, especially at higher doses
  • Subclinical liver injury is common (28% of patients) but usually transient 3
  • Most cases of severe liver injury are associated with doses ≥300 mg/day 1
• Other potential side effects: vasculitis and thrombocytopenia 2

Comparative Efficacy

• MMI 30 mg/day normalizes FT4 more effectively than PTU 300 mg/day (96.5% vs. 78.3% at 12 weeks) 4
• For mild to moderate hyperthyroidism, methimazole may be preferable due to better efficacy and safety profile 4

Mechanism of Action

• PTU inhibits peripheral deiodination of T4 to T3, reducing extrathyroidal T3 production 5, 6
• This mechanism is unique to PTU and not shared by methimazole

Thyroid Storm Management

• PTU is part of standard treatment for thyroid storm, along with:
  • Beta blockers (propranolol 60-80 mg orally every 4-6 hours or 1-2 mg IV)
  • Saturated solution of potassium iodide or sodium iodide
  • Dexamethasone
  • Supportive care (oxygen, antipyretics, monitoring) 7

Remember that while PTU is effective for hyperthyroidism treatment, its use requires careful monitoring for potential adverse effects, particularly hepatotoxicity and agranulocytosis. In non-pregnant adults with uncomplicated hyperthyroidism, methimazole may be preferable due to its better efficacy and safety profile.