What are the guidelines for monitoring patients on Methimazole (MMI) therapy?

From the Guidelines

Methimazole monitoring should include baseline complete blood count (CBC), liver function tests (LFTs), and thyroid function tests (TFTs) before starting therapy, followed by TFTs every 4-6 weeks until euthyroidism is achieved, then every 2-3 months thereafter. When monitoring methimazole, it is essential to check for symptoms of agranulocytosis (fever, sore throat, mouth ulcers) or hepatotoxicity (jaundice, abdominal pain, dark urine) and perform CBC and LFTs if these symptoms develop 1. The initial dose of methimazole is typically 10-30mg daily divided into 2-3 doses, which can be reduced to maintenance doses of 5-15mg daily once euthyroidism is achieved. Patients should be educated about potential side effects, including rash, pruritus, arthralgias, and the rare but serious complications of agranulocytosis (0.2-0.5% of patients) and hepatotoxicity. Some key points to consider when monitoring methimazole include:

• Routine monitoring of white blood cell counts is not recommended in asymptomatic patients as agranulocytosis typically develops rapidly 1.
• Methimazole works by inhibiting thyroid peroxidase, preventing the incorporation of iodine into thyroglobulin and reducing thyroid hormone synthesis, with clinical improvement typically seen within 4-8 weeks of starting therapy.
• Achieving euthyroidism before pregnancy is crucial, as hyperthyroidism can result in significant maternal and neonatal morbidity, and outcomes correlate with disease control 1. It is also important to note that propylthiouracil is preferred in the first trimester, while methimazole is preferred in the second and third trimesters due to possible teratogenicity in the first trimester with methimazole and propylthiouracil-associated hepatotoxicity in subsequent trimesters 1.

From the FDA Drug Label

Patients who receive methimazole should be under close surveillance and should be cautioned to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. In such cases, white-blood-cell and differential counts should be obtained to determine whether agranulocytosis has developed Laboratory Tests Because methimazole may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy with the drug, especially before surgical procedures. Thyroid function tests should be monitored periodically during therapy

• Monitoring parameters:
  • White-blood-cell and differential counts to check for agranulocytosis
  • Prothrombin time to check for hypoprothrombinemia and bleeding
  • Thyroid function tests to monitor hyperthyroidism
• Monitoring frequency: Periodically during therapy, especially before surgical procedures 2

From the Research

Methimazole Monitoring

• Methimazole is a medication used to treat hyperthyroidism, which is an excessive concentration of thyroid hormones in tissues 3.
• The medication works by reducing the production of thyroid hormones, and its use can be associated with abnormal liver function tests (LFTs) 4.
• Studies have shown that methimazole treatment can result in normalization of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in most patients with baseline abnormal LFTs 4.
• However, methimazole treatment can also induce insignificant LFT elevation, <2× the upper limit of normal (ULN), in some patients 4.
• The choice of treatment for hyperthyroidism, including methimazole, depends on the underlying diagnosis, the presence of contraindications, the severity of hyperthyroidism, and the patient's preference 3.
• In critically ill patients with thyroid storm, methimazole has been compared to propylthiouracil, and no significant differences were found in mortality or adverse events between the two treatment groups 5.

Liver Function Tests

• Abnormal LFTs are common in patients with hyperthyroidism, and methimazole treatment can affect LFT levels 4.
• A study found that 32.5% of patients with newly diagnosed overt hyperthyroidism had abnormal LFTs at baseline, and methimazole treatment resulted in normalization of serum ALT and AST levels in most patients 4.
• However, 13 patients with normal baseline LFTs had <2× the ULN elevations of LFTs sometime during methimazole treatment 4.

Treatment Outcomes

• Methimazole is an effective treatment for hyperthyroidism, and its use can be safely administered in patients with abnormal LFTs 4.
• A comparative effectiveness study found no significant differences in mortality or adverse events between patients treated with methimazole and those treated with propylthiouracil for thyroid storm 5.