What is a complication of methimazole (antithyroid medication) therapy?

Major Complications of Methimazole Therapy

Agranulocytosis is a potentially life-threatening complication of methimazole therapy that requires immediate medical attention and discontinuation of the medication. 1

Serious Hematologic Complications

• Agranulocytosis occurs in patients taking methimazole regardless of dose, age, duration of treatment, or whether it's a first or second exposure to the medication 2
• Patients should be instructed to immediately report symptoms suggestive of agranulocytosis, such as fever or sore throat, which warrant prompt medical evaluation 1
• Other serious hematologic complications include leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) 1, 3
• Agranulocytosis can develop even after discontinuation of methimazole, as demonstrated in case reports where patients developed neutropenia weeks after stopping the medication 4
• Older age, female sex, and higher doses of methimazole may increase the risk of developing agranulocytosis 5

Hepatotoxicity

• Hepatotoxicity, including acute liver failure, can occur with methimazole, although the risk appears to be lower than with propylthiouracil, especially in pediatric populations 1
• Symptoms of hepatic dysfunction include anorexia, pruritus, and right upper quadrant pain 1
• Liver function tests should be monitored during therapy, and the drug should be promptly discontinued if clinically significant liver abnormalities develop, particularly if hepatic transaminases exceed 3 times the upper limit of normal 1

Vasculitis and Autoimmune Complications

• Severe vasculitis can occur with methimazole therapy, potentially resulting in serious complications 1
• Manifestations of vasculitis include leukocytoclastic cutaneous vasculitis, acute kidney injury, glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy 1
• Many cases are associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis 1
• Various autoimmune diseases can be induced by methimazole therapy, including systemic lupus erythematosus, type 1 diabetes mellitus, and thyroid diseases 6

Pregnancy-Related Complications

• Methimazole crosses the placental membrane and can cause fetal harm when administered in the first trimester of pregnancy 1
• Rare congenital defects associated with first-trimester methimazole exposure include:
  • Aplasia cutis (skin defects)
  • Craniofacial malformations (facial dysmorphism, choanal atresia)
  • Gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula)
  • Omphalocele and abnormalities of the omphalomesenteric duct 1

Clinical Management of Complications

• For suspected agranulocytosis, immediately discontinue methimazole and monitor bone marrow indices 1
• Empiric broad-spectrum antibiotics should be initiated promptly in patients with agranulocytosis who develop signs of infection 7
• Granulocyte colony-stimulating factor (G-CSF) may be used to help resolve neutropenia in cases of agranulocytosis 3, 7
• For vasculitis, discontinue therapy and consider additional treatments such as corticosteroids, immunosuppressants, or plasmapheresis in severe cases 1
• Regular monitoring of thyroid function tests is essential to prevent hypothyroidism, another potential complication of methimazole therapy 1

Prevention and Monitoring

• Patients should be under close surveillance and instructed to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise 1
• White blood cell counts with differential should be obtained if symptoms suggestive of agranulocytosis develop 1
• Particular caution should be exercised with patients receiving additional drugs known to cause agranulocytosis 1
• Prothrombin time should be monitored during therapy, especially before surgical procedures, as methimazole may cause hypoprothrombinemia and bleeding 1