What is the use of Methimazole (MMI)?

From the Guidelines

Methimazole should be used with caution in pregnancy, particularly in the first trimester, due to potential birth defects, and propylthiouracil is preferred during this period 1. When treating hyperthyroidism, methimazole is a commonly used medication, especially for conditions like Graves' disease. The goal of treatment is to maintain FT4 or FTI in the high-normal range using the lowest possible thioamide dosage, as stated in the American Family Physician guidelines 1.

Key Considerations

• The typical starting dose of methimazole ranges from 10-30mg daily, divided into three doses for severe cases or given once daily for milder cases, with maintenance doses usually between 5-15mg daily.
• Treatment typically continues for 12-18 months, with dosage adjustments based on thyroid function tests performed every 4-6 weeks initially.
• Methimazole works by blocking the enzyme thyroperoxidase, which is essential for thyroid hormone production, thereby reducing excessive thyroid hormone levels in the bloodstream.
• Common side effects include rash, itching, joint pain, and gastrointestinal disturbances.
• Rare but serious side effects include agranulocytosis (severe decrease in white blood cells), liver damage, and vasculitis.
• Patients should be advised to seek immediate medical attention if they develop fever, sore throat, unusual bleeding or bruising, or yellowing of the skin or eyes.

Pregnancy Considerations

• Methimazole is contraindicated during the first trimester of pregnancy due to potential birth defects, and propylthiouracil is preferred during this period 1.
• Propylthiouracil is preferred in the first trimester, while methimazole is preferred in the second and third trimesters due to the risk of hepatotoxicity associated with propylthiouracil 1.
• Regular monitoring of complete blood counts and liver function is recommended during treatment.
• Women treated with propylthiouracil or methimazole can breastfeed safely, as stated in the American Family Physician guidelines 1.

From the FDA Drug Label

In patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option. To ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy. Methimazole inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism.

Methimazole is used to treat hyperthyroidism in patients with Graves’ disease or toxic multinodular goiter. The main mechanism of action is to inhibit the synthesis of thyroid hormones. Key points include:

• Indications: Graves’ disease with hyperthyroidism, toxic multinodular goiter
• Mechanism of action: Inhibits thyroid hormone synthesis
• Use: To ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy 2, 2

From the Research

Methimazole Dosage and Efficacy

• The effectiveness of methimazole in treating hyperthyroidism due to Graves' disease has been studied in various dosages, including a small single daily dose of 15 mg and a conventional divided dose of 10 mg three times daily 3, 4.
• Studies have shown that a single daily dose of 15 mg methimazole is effective in achieving euthyroidism in most patients with Graves' hyperthyroidism, with a mean time to achieve euthyroidism of around 5-6 weeks 3, 4, 5.
• A comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease found that methimazole 30 mg/d was more effective in normalizing serum free T4 levels than propylthiouracil 300 mg/d and methimazole 15 mg/d, especially in patients with severe hyperthyroidism 6.

Methimazole Dosage and Side Effects

• The incidence of side effects, including agranulocytosis, has been found to be higher with an initial dose of 30 mg daily of methimazole compared to 15 mg daily 7.
• A study found that the prevalence of methimazole-induced agranulocytosis was significantly higher in patients who received 30 mg/d of methimazole compared to those who received 15 mg/d (0.814% vs. 0.219%, respectively) 7.
• Another study found that adverse effects occurred more frequently in patients treated with conventional divided doses (10 mg 3 times daily) compared to a small single daily dose (15 mg once daily) of methimazole (24% vs. 13%, respectively) 5.

Long-term Follow-up and Relapse Rates

• A prospective long-term follow-up study found that there was no difference in the clinical and immunological course or in the long-term remission rate of Graves' hyperthyroidism when treatment was initiated with either a small single daily dose (15 mg) or the conventional regimen (10 mg 3 times daily) of methimazole 5.
• The study found that the rates of recurrence were similar between the two groups, with 41-63% of patients experiencing recurrence at 1-6 years after treatment was stopped 5.