Methimazole is a thionamide that inhibits peroxidase, thereby disrupting thyroid hormone synthesis. It is used to treat hyperthyroidism.
Peroxidase oxidizes inorganic iodide to organic iodine, which binds tyrosine residues to form monoiodotyrosine (MIT). Peroxidase also catalyzes the coupling of MIT and diiodotryosine (DIT) to form T3 and the coupling of DIT and DIT to form T4. Thionamide toxicities include skin rash and rarely agranlocytosis. Methimazole is a possible teratogen in pregnancy however it is sometimes used in the 2nd and 3rd trimesters to manage hyperthyroid states such as Grave's disease. Its use could lead to fetal hypothyroidism creating a potential for Cretinism to occur. Alternative treatment options for hyperthyroidism include ablative thyroid therapy with iodine-131.
Reid and Wheeler review hyperthyroidism. Graves' disease is the most common cause of hyperthyroidism. Other common causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of medications. The diagnostic workup for hyper and hypothyroidism begins with checking thyroid-stimulating hormone (TSH) levels. Radioactive iodine is the treatment of choice for hyperthyroidism, but thyroid drugs may be used in the short-term or in patients with contraindications to radiotherapy.
Azzizi reviews the use of thionamides. Although experts more often consider radioiodine to be the treatment of choice for hyperthyroidism because of its safety and ease of administration, thionamides are the treatment of choice in thyrotoxic children, adolescents, and hyperthyroid women during pregnancy, the postpartum period and lactation.
Illustration A diagrams thyroid hormone synthesis. Thyroid peroxidase couples MIT and DIT in the oxidation step seen at the center-left of the image.
Answer 1: Thyroxine-binding globulin (TBG) binds T3 and T4 in blood. Blocking its action would likely increase free T3 and T4 and therefore exacerbate hyperthyroidism.
Answer 2: Sex-hormone binding globulin (SHBG) binds sex hormones in the blood and would likely have little effect on free levels of T3 or T4.
Answer 4: 5’ deiodinase converts T4 to T3 in peripheral tissues. Propylthiouracil (another thionamide) inhibits 5’ deiodinase, but methimazole does not.
Answer 5: The sodium-iodide symporter actively transports iodide through the basement membrane of thyroid follicular cells. Its action is not inhibited by methimazole.
Reid JR, Wheeler SF. Hyperthyroidism: diagnosis and treatment. Am Fam Physician. 2005 Aug 15;72(4):623-30. Review.
PMID:16127951 (Link to Abstract)
Azizi F. The safety and efficacy of antithyroid drugs. Expert Opin Drug Saf. 2006 Jan;5(1):107-16. Review. PubMed PMID: 16370960
PMID:16370960 (Link to Abstract)