What is the recommended treatment and dosage for hyperthyroidism using Methimazole?

Methimazole Treatment for Hyperthyroidism

For hyperthyroidism, initiate methimazole at 15 mg daily for mild disease, 30-40 mg daily for moderate disease, and 60 mg daily for severe hyperthyroidism, divided into three doses at 8-hour intervals, with a maintenance dose of 5-15 mg daily once euthyroid. 1

Initial Dosing Strategy

Adult dosing should be stratified by disease severity:

• 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

Pediatric dosing: 0.4 mg/kg body weight daily divided into 3 doses at 8-hour intervals, with maintenance at approximately half the initial dose 1

Evidence for Single Daily Dosing

While the FDA label recommends divided dosing, research demonstrates that single daily dosing is highly effective and may reduce adverse effects. A single daily dose of 15 mg methimazole achieved euthyroidism in 93% of patients within 12 weeks, with mean time to euthyroidism of 5.3 weeks 2. For severe hyperthyroidism (free T4 ≥7 ng/dL), 30 mg daily as a single dose normalized thyroid function more effectively than 15 mg daily 3.

Treatment Goals and Monitoring

The primary goal is maintaining free T4 or Free Thyroxine Index (FTI) in the high-normal range using the lowest possible thioamide dosage. 4, 5

Monitoring schedule:

• Check free T4 or FTI every 2-4 weeks during initial treatment to adjust dosing 4, 5
• Once stable on maintenance therapy, continue monitoring to prevent over-suppression 4

Maintenance dosing: Reduce to 5-15 mg daily once euthyroidism is achieved 1

Symptomatic Management

Beta-blockers (e.g., propranolol) should be used concurrently until thyroid hormone levels normalize to control symptoms such as tachycardia, tremor, and anxiety. 4, 5

Factors Affecting Treatment Response

Response to methimazole is influenced by:

• Goiter size: Larger goiters require longer time to achieve euthyroidism 6
• Pretreatment T3 levels: Higher initial thyroid hormone levels predict delayed response 6, 3
• Methimazole dose: Higher doses (30-40 mg) achieve faster normalization than 15 mg in severe disease 6, 3
• Iodine status: Urinary iodide excretion ≥100 mcg/g creatinine delays response 6

In patients with severe hyperthyroidism (free T4 ≥5 ng/dL), combining methimazole 15 mg with inorganic iodine 38 mg daily achieved euthyroidism faster than methimazole 30 mg alone (45.3% vs 24.8% at 30 days) with fewer adverse effects requiring discontinuation (7.5% vs 14.8%) 7. However, iodine should be discontinued once free T4 normalizes 7.

Critical Adverse Effects and Monitoring

Agranulocytosis is the most serious adverse effect, typically presenting with sore throat and fever. 4

If sore throat and fever develop:

• Obtain complete blood count immediately 4
• Discontinue methimazole 4
• Do not restart thioamide therapy if agranulocytosis confirmed 4

Other significant adverse effects include:

• Hepatitis 4
• Vasculitis 4
• Thrombocytopenia 4

Adverse effects are dose-dependent: Higher doses (30 mg) cause more adverse effects than lower doses (15 mg), with mild hepatotoxicity being particularly common at higher doses 3. Single daily dosing of 15 mg caused adverse effects in only 2 patients compared to 6 patients on 30 mg in one study 2.

Special Populations

Pregnancy

Methimazole can be used during pregnancy, though propylthiouracil is often preferred in the first trimester due to methimazole's association with rare congenital anomalies. 4

• Maintain free T4 or FTI in the high-normal range using the lowest possible dose 4
• Monitor every 2-4 weeks 4
• Fetal thyroid suppression is usually transient and rarely requires treatment 4
• Women can safely breastfeed while taking methimazole 4

Thyroid Storm

In thyroid storm, methimazole (or propylthiouracil) is part of a multi-drug regimen including saturated solution of potassium iodide or sodium iodide, dexamethasone, and supportive measures. 4

Comparative Efficacy

Methimazole 30 mg daily is superior to propylthiouracil 300 mg daily for achieving euthyroidism, particularly in severe hyperthyroidism. At 12 weeks, methimazole 30 mg normalized free T4 in 96.5% of patients versus 78.3% with propylthiouracil 300 mg 3. Single daily dose of 15 mg methimazole was also more effective than 150 mg propylthiouracil daily, with significantly lower thyroid hormone levels after 4 weeks 8.