What is the recommended treatment for hyperthyroidism using methimazole?

Methimazole Treatment for Hyperthyroidism

Methimazole is the preferred antithyroid drug for hyperthyroidism, dosed initially at 10-40 mg daily (depending on severity) with the goal of maintaining free T4 in the high-normal range using the lowest effective dose. 1, 2

Indications

Methimazole is indicated for:

• Graves' disease or toxic multinodular goiter when surgery or radioactive iodine is not appropriate 2
• Preparation for thyroidectomy or radioactive iodine therapy 2
• First-line therapy in pregnant women (especially 2nd and 3rd trimesters), lactating women, children, and adolescents 2, 3

Dosing Strategy

Initial Dosing

• For moderate to severe hyperthyroidism (free T4 ≥5 ng/dL): Start with 15-30 mg daily 4, 5
• Methimazole 15 mg daily combined with inorganic iodine 38 mg daily achieves faster control than methimazole 30 mg alone, with fewer adverse effects 4
• Single daily dosing is effective and controls hyperthyroidism in most patients 6

Maintenance and Monitoring

• Monitor free T4 or Free Thyroxine Index every 2-4 weeks to adjust dosing 1
• Titrate to the lowest dose that maintains free T4 in the high-normal range 1
• A rising TSH indicates the need for dose reduction 2
• Treatment duration is typically 12-18 months using the titration method 3

Concurrent Symptomatic Management

• Beta-blockers should be used concurrently until thyroid hormone levels normalize to manage symptoms 1
• Beta-blocker doses may need reduction once the patient becomes euthyroid due to decreased clearance 2

Critical Adverse Effects and Monitoring

Major Adverse Effects

• Agranulocytosis, hepatitis, vasculitis, and thrombocytopenia are potential serious complications 1
• Adverse effects requiring discontinuation occur in approximately 7.5-14.8% of patients, with higher rates at 30 mg daily versus 15 mg daily 4
• Monitor prothrombin time before surgical procedures due to risk of hypoprothrombinemia 2

Drug Interactions

• Warfarin activity may be increased; monitor PT/INR closely, especially before surgery 2
• Digitalis and theophylline doses may need reduction as patients become euthyroid 2

Special Populations

Pregnancy

• Methimazole is Pregnancy Category D but is preferred over propylthiouracil in the 2nd and 3rd trimesters 2
• Consider switching from propylthiouracil to methimazole after the first trimester due to PTU hepatotoxicity risk 2
• Use the minimum effective dose to avoid fetal goiter and cretinism 2

Pediatrics

• Methimazole is the preferred antithyroid drug in children due to severe liver injury risk with propylthiouracil 2

Lactation

• Methimazole is present in breast milk but long-term studies show no toxicity in nursing infants 2
• Monitor infant thyroid function weekly or biweekly 2

Clinical Pearls

• Approximately 50% of patients relapse after 12-18 months of therapy, requiring ablative treatment 3
• Methimazole does not inactivate existing thyroid hormone stores; it only inhibits new synthesis 2
• Discontinue iodine supplementation once free T4 normalizes if using combination therapy 4