From the Guidelines
Methimazole works by inhibiting the enzyme thyroid peroxidase, which is essential for thyroid hormone synthesis, thereby preventing the production of thyroid hormones T3 and T4. This mechanism of action is crucial in treating hyperthyroidism, particularly in conditions like Graves' disease, toxic multinodular goiter, and thyrotoxicosis. The inhibition of thyroid peroxidase prevents the oxidation and organification of iodide, blocking the incorporation of iodine into tyrosine residues on thyroglobulin, a critical step in the production of thyroid hormones 1. Additionally, methimazole interferes with the coupling of iodotyrosines, further reducing thyroid hormone synthesis.
The medication is primarily used to treat hyperthyroidism, and its effectiveness is evident in its ability to reduce thyroid hormone levels, although it does not affect already circulating thyroid hormones, so clinical improvement typically takes several weeks as existing hormone levels gradually decline 1. The medication is usually administered orally in doses ranging from 5-60 mg daily, depending on the severity of hyperthyroidism, with higher initial doses often tapered as thyroid function normalizes.
Some key points to consider when using methimazole include:
- Common side effects include rash, pruritus, and gastrointestinal disturbances
- Rare but serious adverse effects include agranulocytosis and hepatotoxicity, as noted in the treatment of hyperthyroidism in pregnancy 1
- Methimazole is preferred in the second and third trimesters, while propylthiouracil is preferred in the first trimester due to possible teratogenicity with methimazole 1
- Monitoring of thyroid function and adjustment of doses is crucial to achieve euthyroidism and prevent maternal and neonatal morbidity.
From the FDA Drug Label
Methimazole inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The mechanism of action (MoA) of methimazole is the inhibition of thyroid hormone synthesis.
- It does not affect existing thyroxine and tri-iodothyronine.
- The drug is effective in treating hyperthyroidism 2
From the Research
Mechanism of Action of Methimazole
- Methimazole (MMI) is an antithyroid drug used to treat hyperthyroidism by inhibiting the synthesis of thyroid hormone at various levels 3.
- The primary mechanism of action of MMI is the inhibition of thyroid peroxidase (TPO), a key enzyme involved in the synthesis of thyroid hormones (TH) 4, 5.
- MMI exerts its effect by inhibiting the TPO-catalyzed iodination of thyroglobulin, which is a crucial step in the synthesis of thyroid hormones 5.
- In addition to its inhibitory effect on TPO, MMI has also been shown to have antioxidant and immunomodulatory effects on thyroid cells, involving the interferon-gamma signaling pathway and H2O2 scavenging 6.
Inhibition of Thyroid Hormone Synthesis
- MMI inhibits the formation of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) by inhibiting the coupling reaction between two molecules of 3,5-diiodotyrosine (DIT) 5.
- The inhibition of T4 and T3 formation by MMI is dose-dependent, and the drug can exert a specific inhibitory effect on the coupling reaction under certain conditions 5.
Antioxidant and Immunomodulatory Effects
- MMI has been shown to have antioxidant effects by eliminating H2O2 produced by interferon-gamma treatment in thyroid cells, and thus inhibiting the H2O2-mediated phosphorylation of tyrosine 701 in STAT1 6.
- MMI also has immunomodulatory effects by inhibiting the transcription of the intercellular adhesion molecule-1 (ICAM-1) gene, which is involved in the immune response 6.