Antithyroid Drug Dosing for Hyperthyroidism
For adults with hyperthyroidism, initiate methimazole at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, or 60 mg daily for severe hyperthyroidism, divided into three doses at 8-hour intervals, with maintenance dosing of 5-15 mg daily once euthyroid. 1
Initial Dosing Strategy
Methimazole (Preferred Agent)
Methimazole is the first-line antithyroid drug due to lower rates of major adverse effects, once-daily dosing capability, and better cost-effectiveness. 2, 3
- Mild hyperthyroidism: Start 15 mg daily 1
- Moderate hyperthyroidism: Start 30-40 mg daily 1
- Severe hyperthyroidism: Start 60 mg daily 1
- Pediatric dosing: 0.4 mg/kg daily divided into 3 doses at 8-hour intervals 1
The evidence strongly supports that methimazole 30 mg/d achieves normalization of free T4 more effectively than lower doses (15 mg/d) or propylthiouracil 300 mg/d, particularly in severe hyperthyroidism (FT4 ≥7 ng/dL). 4 However, starting doses should not exceed 15-20 mg/d when possible, as agranulocytosis risk is dose-dependent. 2
Propylthiouracil (Alternative Agent)
Propylthiouracil should be reserved for specific situations only: first trimester pregnancy or patients with adverse reactions to methimazole. 5, 2
- Adults: Initial dose 300 mg daily in 3 divided doses 6
- Severe hyperthyroidism/large goiters: May increase to 400 mg daily; occasionally 600-900 mg daily initially 6
- Maintenance: 100-150 mg daily 6
Propylthiouracil carries significant risk of severe liver failure requiring transplantation or causing death, making it unsuitable as a first-line agent. 2
Maintenance and Monitoring
- Maintenance methimazole: Approximately 5-15 mg daily, which is roughly half the initial dose 1
- Monitor thyroid function every 2-4 weeks during initial treatment to assess response 5
- Adjust dosing to maintain free T4 or free T3 in the high-normal range using the lowest effective thioamide dose 5
Special Populations
Pregnancy
In pregnant women, use the lowest possible thioamide dosage to maintain FT4 or FTI in the high-normal range. 5 Propylthiouracil is preferred in the first trimester due to methimazole's association with aplasia cutis and choanal/esophageal atresia. 3 Both agents are safe for breastfeeding. 5
Thyroid Storm
For thyroid storm, use propylthiouracil or methimazole as part of a multi-drug regimen including saturated solution of potassium iodide or sodium iodide, dexamethasone, and supportive measures. 5 Treatment should not be delayed for laboratory confirmation. 5
Immune Checkpoint Inhibitor-Related Thyrotoxicosis
For persistent thyrotoxicosis (>6 weeks) in patients on immune checkpoint inhibitors with severe symptoms (Grade 3-4), consider thionamides (methimazole or propylthiouracil) after endocrine consultation. 5 Most cases are self-limited thyroiditis requiring only beta-blockers and supportive care. 5
Critical Safety Considerations
Monitor for agranulocytosis: If sore throat and fever develop, obtain complete blood count immediately and discontinue the thioamide. 5 Other serious adverse effects include hepatitis, vasculitis, and thrombocytopenia. 5
Noncompliance is the most common reason for treatment failure with massive doses of propylthiouracil; consider switching to methimazole rather than escalating propylthiouracil doses further. 7
Development of low TSH during therapy suggests overtreatment or recovery of thyroid function—reduce dose or discontinue with close follow-up. 5