What is the initial dose of methimazole (antithyroid medication) and propylthiouracil (antithyroid medication) for treating hyperthyroidism?

Initial Dosing of Antithyroid Medications for Hyperthyroidism

For methimazole, start with 15 mg daily for mild hyperthyroidism, 30-40 mg daily for moderate disease, and 60 mg daily for severe hyperthyroidism, given as a single daily dose or divided into three doses at 8-hour intervals. 1

Methimazole Dosing Strategy

Adult Initial Dosing

• Mild hyperthyroidism: 15 mg daily 1
• Moderately severe hyperthyroidism: 30-40 mg daily 1
• Severe hyperthyroidism: 60 mg daily 1
• Doses can be given as a single daily dose or divided into 3 doses at 8-hour intervals 1

Key Dosing Principle

The starting dose of methimazole should not exceed 15-20 mg/day when possible, as the risk of agranulocytosis is dose-dependent. 2 Research demonstrates that intrathyroidal concentrations of methimazole plateau at doses above 15 mg/day due to saturable uptake mechanisms, and single daily dosing of 15 mg is effective in 93% of patients with Graves' disease. 3, 4

Maintenance Dosing

• Typical maintenance dose: 5-15 mg daily 1
• Adjust based on thyroid function tests repeated every 4-6 weeks during initial treatment 5

Pediatric Dosing

• Initial: 0.4 mg/kg/day divided into 3 doses at 8-hour intervals 1
• Maintenance: Approximately half of the initial dose 1

Propylthiouracil (PTU) Dosing Strategy

Adult Initial Dosing

• Standard initial dose: 300 mg daily 6
• Severe hyperthyroidism or very large goiters: 400 mg daily; occasionally 600-900 mg daily may be required 6
• Maintenance dose: 100-150 mg daily 6
• All doses divided into 3 equal doses at 8-hour intervals 6

Critical Safety Warning

Propylthiouracil should NOT be used as a first-line agent due to risk of severe liver failure requiring transplantation or causing death. 2 PTU is only recommended when antithyroid treatment is needed during the first trimester of pregnancy or when patients have experienced adverse reactions to methimazole. 2

Pediatric Considerations

• PTU is generally not recommended in pediatric patients except in rare instances 6
• If used in patients ≥6 years: start at 50 mg daily with careful upward titration 6
• Most severe liver injury cases occurred with doses ≥300 mg/day 6

Practical Management Approach

Symptomatic Control

• Add a beta-blocker (atenolol 25-50 mg daily or propranolol) for symptomatic relief while awaiting thyroid hormone normalization 7, 5
• Beta-blockers are particularly useful in the hyperthyroid phase of thyroiditis 7

Monitoring Schedule

• Check thyroid function (TSH and free T4) every 4-6 weeks during initial treatment and dose adjustment 5
• Monitor for agranulocytosis symptoms (sore throat, fever) which requires immediate drug discontinuation 5

When to Consider Alternative Therapy

• If TSH-receptor antibodies remain >10 mU/L after 6 months of treatment, remission is unlikely and radioactive iodine or thyroidectomy should be considered 2
• Consult endocrinology for persistent thyrotoxicosis lasting >6 weeks 5

Common Pitfalls to Avoid

• Do not use excessive methimazole doses: Single daily doses of 15 mg are as effective as higher doses (30 mg) but cause fewer side effects 3
• Do not use PTU as first-line: Reserve for first trimester pregnancy or methimazole intolerance only 2
• Do not overlook agranulocytosis: Educate all patients to report sore throat and fever immediately 5
• Do not continue radioiodine prep medications: Stop antithyroid drugs at least one week before radioiodine therapy to reduce treatment failure risk 2