Hyperthyroidism Treatment Approach and Dosing
For hyperthyroidism, initiate methimazole at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, or 60 mg daily for severe disease, divided into three doses at 8-hour intervals, then maintain at 5-15 mg daily once euthyroid. 1
Initial Treatment Selection
Methimazole is the preferred first-line antithyroid drug for most patients with hyperthyroidism due to lower rates of major side effects, once-daily dosing convenience, lower cost, and better availability compared to propylthiouracil (PTU). 2, 3
Methimazole Dosing Protocol
Initial dosing based on disease severity: 1
- Mild hyperthyroidism: 15 mg daily
- Moderately severe hyperthyroidism: 30-40 mg daily
- Severe hyperthyroidism: 60 mg daily
- Divide total daily dose into 3 administrations at 8-hour intervals
Critical safety consideration: The starting dose should not exceed 15-20 mg daily to minimize the dose-dependent risk of agranulocytosis. 2 However, the FDA label supports higher initial doses for moderate-to-severe disease. 1
Maintenance Phase
Target maintenance dose is 5-15 mg daily to keep free T4 or free thyroxine index in the high-normal range using the lowest effective dose. 4
Monitoring schedule: 4
- Check free T4 or FTI every 2-4 weeks during initial treatment phase
- Adjust dose based on thyroid function tests to maintain target levels
- Once biochemically stable, extend monitoring intervals to every 6-12 months
- TSH normalization may lag behind T4 normalization by several weeks to months
Propylthiouracil: Limited Role
PTU should NOT be used as first-line therapy due to risk of severe liver failure requiring transplantation or causing death. 2
PTU is reserved only for: 2, 3
- First trimester of pregnancy (to avoid methimazole-associated aplasia cutis and choanal/esophageal atresia)
- Patients who have experienced adverse responses to methimazole
PTU dosing when indicated: 5
- Initial dose: 300 mg daily (may increase to 400 mg daily for severe disease or very large goiters; occasionally 600-900 mg daily)
- Maintenance dose: 100-150 mg daily
- Administer in 3 equal doses at 8-hour intervals
Treatment Duration and Definitive Therapy
Standard antithyroid drug course is 12-18 months for Graves' disease with the goal of inducing long-term remission. 6, 7
Predictors of recurrence after stopping antithyroid drugs: 7
- Age younger than 40 years
- FT4 concentrations ≥40 pmol/L at diagnosis
- TSH-binding inhibitory immunoglobulins >6 U/L
- Goiter size ≥WHO grade 2
Consider definitive therapy (radioiodine or thyroidectomy) when: 4, 7
- TSH-receptor antibodies remain >10 mU/L after 6 months of treatment
- Patient fails to achieve control on 15 mg daily after 4-6 weeks; consider escalation to 30-40 mg daily in divided doses
- Recurrence occurs after initial course (approximately 50% of patients)
- Long-term treatment (5-10 years) is associated with fewer recurrences (15%) versus short-term treatment
Toxic nodular goiter requires definitive therapy as antithyroid drugs will not cure this condition; radioiodine is the treatment of choice. 6, 7
Critical Safety Monitoring
Agranulocytosis is the most serious adverse effect of methimazole, typically presenting with sore throat and fever. 4
Immediate action required: 4
- Obtain complete blood count immediately if symptoms develop
- Discontinue methimazole if agranulocytosis is confirmed
Other serious adverse effects to monitor: 4
- Hepatitis
- Vasculitis
- Thrombocytopenia
Special Populations
Pregnancy
Both methimazole and PTU are effective with no significant differences in neonatal outcomes overall, but PTU is preferred in first trimester due to methimazole's association with congenital anomalies. 4, 3
- Use lowest possible dose to maintain free T4 in high-normal range
- Both drugs are safe for breastfeeding
- Monitor fetal growth and maternal heart rate regularly
Pediatric Patients
Methimazole initial dosing: 0.4 mg/kg body weight divided into 3 doses at 8-hour intervals 1
- Maintenance: approximately half of initial dose
- PTU is generally not recommended in pediatric patients except when alternative therapies are inappropriate 5
Geriatric Patients
Use cautious dose selection reflecting greater frequency of decreased hepatic, renal, or cardiac function. 5