Thionamides (PTU vs Methimazole)

Summary

Propylthiouracil, shortened as PTU, and Methimazole are thionamide drugs that are used in the treatment of hyperthyroidism. They work by inhibiting the enzyme thyroid peroxidase, which prevents the organification or coupling of oxidized iodide to thyroglobulin in order to form thyroid hormones. PTU specifically also has a second mechanism of blocking the peripheral conversion of T4 to T3. All of these mechanisms are useful in the treatment of hyperthyroidism. An adverse effect of both drugs is bone marrow suppression, which presents in a variety of ways, including agranulocytosis and anemia. PTU specifically may cause life-threatening hepatotoxicity, while methimazole specifically acts as a teratogen during pregnancy. Due to these side effects, methimazole is preferred over PTU for the treatment of hyperthyroidism, except during pregnancy.

Key Points

• Propylthiouracil (PTU) and Methimazole
  • Also called Thionamides
  • Mechanism
    • Both inhibit thyroid peroxidase (thyroperoxidase)
      • Reduce thyroid hormone synthesis
        • Thyroid hormone is formed by the coupling of oxidized iodide (MIT and DIT) to thyroglobulin (TG), in a process called “organification”
          • one MIT (M = mono = 1) and one DIT (D = di = 2) are coupled to TG to form T3 (1+2 = T3), while two DIT are used to form T4 (2+2 = T4)
        • Both drugs block oxidation and coupling of iodide to thyroglobulin to form thyroid hormone
    • PTU decreases peripheral conversion of T4 to T3
      • blocks 5’-deiodinase, which converts the less active T4 into more active T3
      • NOT seen with methimazole
  • Indications
    • Hyperthyroidism
  • Adverse Effects
    • Bone marrow suppression (agranulocytosis)
      • While anemia is far more common, agranulocytosis (neutropenia) is feared and typically presents with sore throat, followed by devastating systemic infections
    • PTU only: hepatotoxicity
      • Accordingly, methimazole is first-line (not PTU) for hyperthyroidism
    • Methimazole only: teratogen
      • Methimazole use in pregnancy associated with birth defects (esophageal atresia, developmental delay)
      • Accordingly, PTU is first-line in pregnant and breast-feeding mothers (methimazole enters breast milk), although dosage must be titrated carefully to prevent fetal hypothyroidism (cretinism)
    • Edema and skin rash may be seen