What is the mechanism of action of methimazole in treating hyperthyroidism?

Mechanism of Action of Methimazole in Treating Hyperthyroidism

Methimazole works by inhibiting the synthesis of thyroid hormones through blocking the organification of iodine in the thyroid gland, which effectively treats hyperthyroidism without affecting existing circulating thyroid hormones. 1

Primary Mechanism

• Methimazole (MMI) is a thioamide antithyroid drug that specifically inhibits the synthesis of new thyroid hormones 1, 2
• It blocks the iodine organification process in the thyroid gland, preventing the incorporation of iodine into thyroglobulin 1, 3
• The drug does not inactivate or affect existing thyroxine (T4) and triiodothyronine (T3) that are already stored in the thyroid gland or circulating in the bloodstream 1
• MMI also does not interfere with the effectiveness of exogenous thyroid hormones given orally or by injection 1

Pharmacokinetics

• Methimazole is readily absorbed in the gastrointestinal tract after oral administration 1
• It is metabolized primarily in the liver 1
• The drug is excreted in the urine 1
• MMI has a longer half-life compared to propylthiouracil (PTU), allowing for once-daily dosing in most cases 2, 4

Clinical Application

• Methimazole is the drug of choice for treating hyperthyroidism due to its:

  • Longer half-life allowing for once-daily dosing 2, 4
  • Lower incidence of severe side effects compared to other antithyroid medications 2
  • Effective control of hyperthyroidism at relatively low doses (15mg daily) 4

• The goal of treatment is to maintain free T4 or Free Thyroxine Index (FTI) in the high-normal range using the lowest possible thioamide dosage 5

Dosing Considerations

• Initial dosing typically ranges from 15-30mg daily depending on the severity of hyperthyroidism 6, 4
• Single daily dosing of 15mg has been shown to be effective in most patients with Graves' hyperthyroidism while causing fewer adverse effects than higher doses 4
• Monitoring of free T4 or FTI every 2-4 weeks is recommended to adjust dosing appropriately 5

Important Clinical Considerations

• Methimazole crosses the placenta and requires careful consideration during pregnancy 3
• Potential adverse effects include agranulocytosis (presenting with sore throat and fever), hepatitis, vasculitis, and thrombocytopenia 5
• Methimazole is preferred over propylthiouracil in most cases due to its more favorable safety profile 2
• Beta-blockers may be used concurrently until thyroid hormone levels are reduced to manage symptoms 5