What is the purpose of Methimazole (antithyroid medication) in treating hyperthyroidism?

Methimazole Purpose in Treating Hyperthyroidism

Methimazole inhibits thyroid hormone synthesis and is the preferred first-line antithyroid medication for treating hyperthyroidism caused by Graves' disease and toxic multinodular goiter. 1

Mechanism of Action

• Methimazole blocks the synthesis of new thyroid hormones by inhibiting thyroid peroxidase, the enzyme responsible for incorporating iodine into thyroid hormone precursors 1
• The drug does not inactivate existing thyroxine (T4) and triiodothyronine (T3) already stored in the thyroid gland or circulating in the bloodstream 1
• It does not interfere with the effectiveness of exogenous thyroid hormones given orally or by injection 1

Clinical Indications

Methimazole is FDA-approved for two primary purposes: 1

• Primary treatment in patients with Graves' disease or toxic multinodular goiter when surgery or radioactive iodine therapy is not appropriate 1
• Preparatory treatment to ameliorate hyperthyroid symptoms before thyroidectomy or radioactive iodine therapy 1

Treatment Approaches and Duration

• For long-term primary therapy, methimazole is typically used for 1-2 years with the goal of achieving remission 2
• For preparatory therapy before definitive treatment (surgery or radioiodine), methimazole is used short-term for weeks to months 2
• The medication is readily absorbed in the gastrointestinal tract, metabolized in the liver, and excreted in the urine 1

Dosing Strategy

• Initial dosing typically ranges from 10-30 mg daily as a single dose 2
• Methimazole has a significant advantage over propylthiouracil (PTU) because it can be administered once daily, improving patient adherence 2, 3
• For severe hyperthyroidism (free T4 ≥7 ng/dL), 30 mg daily is more effective than lower doses at normalizing thyroid function by 8-12 weeks 4
• For mild to moderate hyperthyroidism, 15 mg daily is appropriate and causes fewer adverse effects than higher doses 4

Comparative Effectiveness

• Methimazole is superior to propylthiouracil in achieving euthyroidism: a single daily dose of 15 mg methimazole is more effective than 150 mg PTU daily in normalizing thyroid hormones 3
• Methimazole reduces thyrotropin receptor antibodies (TRAb) more effectively than PTU after 8 weeks of treatment 3
• Approximately 80% of patients achieve euthyroid status within 8 weeks of starting methimazole therapy 5

Why Methimazole is Preferred Over PTU

Methimazole is the drug of choice for most patients because: 2

• Major adverse effects are less common compared to PTU 2
• Once-daily dosing improves compliance versus PTU's requirement for dosing every 6 hours 2
• It is less expensive and more widely available 2
• Lower doses (15 mg daily) cause significantly fewer adverse effects than higher doses while maintaining efficacy 4, 6

Important Exception: Pregnancy

• PTU is preferred over methimazole during the first trimester of pregnancy 2
• Methimazole has been associated with rare congenital anomalies including aplasia cutis and choanal/esophageal atresia 2
• Both medications have similar placental transfer kinetics and therapeutic efficacy in pregnancy 2
• Both are present in breast milk but are not contraindicated during lactation 2

Monitoring and Maintenance

• The goal is to maintain free T4 or Free Thyroxine Index in the high-normal range using the lowest possible dose 7
• Free T4 or FTI should be monitored every 2-4 weeks during initial treatment to adjust dosing appropriately 7
• Beta-blockers may be used concurrently until thyroid hormone levels normalize to manage symptoms 7
• Once euthyroid, doses are gradually reduced to a maintenance dose (typically 5 mg daily) 5

Adverse Effects to Monitor

• Potential serious adverse effects include agranulocytosis, hepatitis, vasculitis, and thrombocytopenia 7
• Minor adverse effects occur more frequently with higher doses: 62% with 0.9 mg/kg daily versus 9-14% with lower doses in pediatric patients 6
• Mild hepatotoxicity is more common with PTU than methimazole 4

Long-Term Outcomes

• Remission rates after 1-2 years of treatment are similar regardless of whether methimazole is given as a single daily dose or divided doses 5
• Recurrence rates at 6 years are approximately 60-63% regardless of initial dosing regimen 5
• Higher initial doses do not improve long-term remission rates but do increase adverse effects 6