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

Propylthiouracil Dosing for Hyperthyroidism

The FDA-approved initial dose of propylthiouracil (PTU) for adults with hyperthyroidism is 300 mg daily, divided into three equal doses given every 8 hours, with a usual maintenance dose of 100-150 mg daily. 1

Standard Adult Dosing

• Initial therapy: 300 mg daily in 3 divided doses (100 mg every 8 hours) 1
• Severe hyperthyroidism or very large goiters: May increase initial dose to 400 mg daily; occasionally 600-900 mg daily may be required 1
• Maintenance dose: 100-150 mg daily once euthyroid state is achieved 1

The goal is to maintain free T4 (FT4) or free thyroxine index (FTI) in the high-normal range using the lowest possible thioamide dosage, with monitoring every 2-4 weeks during titration 2.

Special Populations

Pregnancy

• PTU is the preferred thioamide in pregnancy, particularly in the first trimester 2
• Use the lowest possible dose to maintain FT4 or FTI in the high-normal range 2
• Monitor FT4 or FTI every 2-4 weeks and adjust dosing accordingly 2
• Beta blockers (e.g., propranolol) can be added temporarily for symptom control until thyroid hormone levels decrease 2
• Women can safely breastfeed while taking PTU 2

Pediatric Patients

• PTU is generally NOT recommended in pediatric patients except in rare instances when alternative therapies are inappropriate 1
• If used in children ≥6 years: initiate at 50 mg daily with careful upward titration based on TSH and free T4 levels 1
• Most severe liver injury cases in children occurred with doses ≥300 mg/day, though cases have been reported with doses as low as 50 mg/day 1

Geriatric Patients

• Use cautious dose selection reflecting greater frequency of decreased hepatic, renal, or cardiac function 1
• Start with lower doses and titrate carefully 1

Evidence-Based Dosing Strategies

High-Dose Regimen

Research suggests that high-dose PTU regimens (500-1200 mg/day maintained throughout treatment with later T3 addition) achieve significantly higher remission rates (75.4%) compared to conventional low-dose regimens (41.6%) 3. This approach may have greater immunosuppressive effects and permit restoration of immune surveillance mechanisms 3.

However, the FDA-approved dosing remains more conservative, and higher doses carry increased risk of hepatotoxicity 1.

Monitoring During Treatment

• Check thyroid function every 2-4 weeks during dose adjustment 2
• Once stable, monitor every trimester in pregnancy 2
• Watch for agranulocytosis (presents with sore throat and fever) - obtain CBC immediately and discontinue PTU if suspected 2
• Monitor for other adverse effects including hepatitis, vasculitis, and thrombocytopenia 2

Critical Safety Considerations

Noncompliance is the most common reason for apparent treatment failure with PTU, even at very high doses (800-2000 mg/day) 4. Before escalating to massive doses, consider switching to methimazole if compliance is suspected 4.

PTU can cause severe autoimmune disease; maintain high suspicion in patients on chronic therapy who develop fever, myalgia, or respiratory symptoms 5. Immediate discontinuation and immunosuppressive therapy may be lifesaving 5.

Thyroid Storm Management

For thyroid storm, PTU is part of a standard drug series but specific dosing should follow emergency protocols with propranolol, iodide solutions, and dexamethasone 2. Treatment should not be delayed for laboratory confirmation 2.