Methimazole Treatment for Hyperthyroidism
For mild hyperthyroidism, start methimazole at 15 mg daily; for moderately severe hyperthyroidism, start 30-40 mg daily; and for severe hyperthyroidism, start 60 mg daily, all divided into three doses at 8-hour intervals, with a maintenance dose of 5-15 mg daily once euthyroid. 1
Initial Dosing Strategy
The FDA-approved dosing provides the foundation for treatment:
- Mild hyperthyroidism: 15 mg daily divided into 3 doses 1
- Moderately severe hyperthyroidism: 30-40 mg daily divided into 3 doses 1
- Severe hyperthyroidism: 60 mg daily divided into 3 doses 1
However, single daily dosing is equally effective and may reduce adverse effects 2, 3. A single daily dose of 15 mg methimazole achieves euthyroidism in 93% of patients within 12 weeks, with fewer side effects than higher doses 2. For severe cases with free T4 ≥7 ng/dL, 30 mg daily as a single dose is more effective than 15 mg 4.
Factors Affecting Response Time
Your dosing decision should account for:
- Goiter size: Larger goiters require higher doses and respond more slowly 5
- Pretreatment T3 levels: Higher initial T3 predicts delayed response 5
- Iodine status: Urinary iodide ≥100 mcg/g creatinine delays response; only 27% achieve euthyroidism within 3 weeks compared to 46% with iodide <50 mcg/g 5
- Disease severity: Patients with free T4 ≥7 ng/dL benefit from 30 mg daily over 15 mg 4
Monitoring Protocol
Check free T4 and TSH every 2-4 weeks during initial treatment until stable 6, 7. The American Academy of Family Physicians emphasizes maintaining free T4 in the high-normal range using the lowest possible dose 6, 7.
- Initial phase: Monitor every 2-4 weeks 6, 7
- Once stable: Extend to every 3-6 months 7
- TSH normalization lags behind T4 by weeks to months, so don't adjust doses based on TSH alone early in treatment 6
Maintenance Therapy
Target maintenance dose is 5-15 mg daily 6, 1. Once free T4 normalizes, gradually reduce to the lowest dose that maintains high-normal free T4 levels 6, 7.
If hyperthyroidism persists on 15 mg daily after 4-6 weeks, escalate to 30-40 mg daily in divided doses 6. If control fails at this dose, refer to endocrinology for radioactive iodine or thyroidectomy 6.
Critical Safety Monitoring
Agranulocytosis is the most serious adverse effect, presenting with sore throat and fever 6, 7. If these symptoms develop:
- Obtain immediate complete blood count 6
- Discontinue methimazole if agranulocytosis confirmed 6
- Other serious effects include hepatitis, vasculitis, and thrombocytopenia 6, 7
Adverse effects are dose-dependent: 14.8% of patients on 30 mg required discontinuation versus 7.5% on 15 mg 8. Mild hepatotoxicity is significantly more common with higher doses 4.
Symptomatic Management
For severe symptoms, add beta-blockers (atenolol or propranolol) for symptomatic relief until methimazole reduces thyroid hormone levels 7. Grade 3-4 symptoms warrant hospitalization and endocrine consultation 7.
Special Populations: Pregnancy and Breastfeeding
Both methimazole and propylthiouracil are effective in pregnancy with no significant differences in neonatal outcomes 6. Use the lowest dose to maintain free T4 in the high-normal range 6, 7.
- Monitor free T4 every 2-4 weeks during pregnancy 7
- Monitor fetal growth and maternal heart rate regularly 6
- Breastfeeding is safe with methimazole 6, 7
Pediatric Dosing
Initial dose: 0.4 mg/kg body weight divided into 3 doses at 8-hour intervals 1. Maintenance dose is approximately half the initial dose 1.