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

Propylthiouracil (PTU) Dosing for Hyperthyroidism

For adults with hyperthyroidism, start PTU at 300 mg daily divided into three equal doses given every 8 hours, with maintenance typically 100-150 mg daily. 1

Initial Dosing Strategy

Standard Adult Dosing

• Initial dose: 300 mg daily in 3 divided doses (100 mg every 8 hours) 1
• For severe hyperthyroidism or very large goiters: increase initial dose to 400 mg daily 1
• Occasional patients may require 600-900 mg daily initially 1
• Maintenance dose: 100-150 mg daily once thyroid function normalizes 1

Pediatric Dosing (Generally Not Recommended)

• PTU is generally not recommended in pediatric patients except when other alternatives are inappropriate 1
• If used in children ≥6 years: start at 50 mg daily with careful upward titration based on TSH and free T4 levels 1
• Most severe liver injury cases occurred with doses ≥300 mg/day 1

Geriatric Dosing

• Use cautious dose selection due to decreased hepatic, renal, or cardiac function 1
• Follow standard adult dosing but monitor closely for adverse effects 1

Administration Schedule

Give PTU in 3 equally divided doses at approximately 8-hour intervals 1. The rationale is that PTU has a short serum half-life of approximately 73-75 minutes 2, requiring frequent dosing to maintain therapeutic levels.

Alternative Dosing Schedules

• More frequent dosing (every 2 hours during waking hours) has been studied and may achieve euthyroid state faster, but is impractical for routine use 3
• Standard 8-hour interval dosing remains the recommended approach 1

Monitoring Protocol

Initial Phase

• Monitor free T4 or Free T4 Index (FTI) every 2-4 weeks during initial treatment 4
• Goal: maintain free T4 or FTI in the high-normal range using the lowest possible dose 4
• Maximum serum PTU concentrations occur within 1 hour after oral administration 2

Ongoing Monitoring

• Continue monitoring until thyroid hormone levels normalize 4
• Watch for agranulocytosis: if patient develops sore throat and fever, obtain complete blood count immediately and discontinue PTU 4

Adjunctive Therapy

Add a beta-blocker (e.g., propranolol) to reduce symptoms until PTU lowers thyroid hormone levels 4. This provides symptomatic relief during the initial weeks of treatment when thyroid hormones remain elevated.

Special Population Considerations

Pregnancy

• PTU is preferred over methimazole during the first trimester due to lower risk of birth defects 4
• Women treated with PTU can breastfeed safely 4

Severe Hyperthyroidism

• Evidence suggests that methimazole 30 mg/d is more effective than PTU 300 mg/d for severe cases (free T4 ≥7 ng/dL), normalizing thyroid function in 96.5% vs 78.3% of patients at 12 weeks 5
• Consider switching to methimazole for severe cases unless contraindicated (e.g., first trimester pregnancy) 5

Common Pitfalls

Non-Compliance

• Poor compliance is the most common reason for treatment failure with PTU 6
• If patients don't respond to large doses (800-2000 mg/d), suspect non-compliance rather than resistance 6
• Consider switching to once-daily methimazole if compliance is an issue 6

Hepatotoxicity Risk

• PTU carries significant hepatotoxicity risk, particularly with prolonged use and higher doses 7
• Most severe liver injury cases occurred with doses ≥300 mg/day, though cases have been reported with doses as low as 50 mg/day 1