Endocrine Abstracts

Introduction: Methimazole is an antithyroid medication which is now considered the first line agent for medical therapy of Graves’ disease. Rare complications of methimazole (<1%) include agranulocytosis, aplastic anemia, nephritis and hepatitis. We would like to report the rare case of the patient with Methimazole-induced hepatitis.

Case Presentation: A 46-year-old woman, who complained of fatigue, loss of appetite, nausea, vomiting, jaundice, dark urine and light-colored stools was admitted to the Department of Gastroenterology and Hepatology. She had a history of Graves’ disease, which has been diagnosed 20 days ago. At diagnosis, the biochemistry was: thyroid-stimulating hormone <0.001 (0.27–4.20 mU/l), free thyroxine (FT4) 61 (12–22 pmol/l) and free triiodothyronine (FT3) 15.4 (3.1–6.8 pmol/l). She had positive thyroid peroxidase and thyrotropin receptor antibodies. She was started treatment with Methimazol 40 mg daily. After starting treatment, she noticed dark urine, then jaundice and stopped the treatment. Currently lab results: bilirubin 698.5 (<19 µmol/l), indirect bilirubin 509.9 (<15.5 µmol/l), direct bilirubin 188.6 (<5.0 µmol/l), ALT 240 (<32 U/l), AST 180 (<31.0U/l), ALP 590 (<110 U/l) and GGT 40 (<30 U/l). At that time, the thyroid function was TSH <0.005, FT4 64 and FT3 11,3 Hepatitis serology was negative for hepatitis A, B and C. She was also negative for anti-mitochondrial antibody, anti-smooth muscle antibody, anti-parietal cell antibody and anti-nuclear antibody. Iron, Ferritin and Ceruloplasmin levels also were in normal range. She refused a liver biopsy. In the light of negative serological investigations for viral hepatitis and for auto-immune hepatitis, the possibility of drug-induced (methimazol) hepatitis was considered. Anti-thyroid medication was withdrawn and the patient was commenced on Propranolol (β-blocker) to control symptoms and given glucocorticoids (Metipred 32 mg, with gradual dose reduction). Dose adjustments were made with lab tests control. After 3 months lab tests (ALT, AST, Bilirubin, GGT, ALP, TSH, FT4, FT3) were normalized and the patient underwent a total thyroidectomy.

Conclusion: Several direct and indirect mechanisms have been suggested as the cause of liver dysfunction in hyperthyroidism. Summarily, these include direct liver toxicity from prolonged exposure to excessive thyroid hormones, liver cell degeneration from accelerated liver glycogen and protein decomposition, autoimmune-related liver injury, congestive hepatopathy from concomitant thyrotoxic heart failure, previous underlying liver disease and antithyroid medication-related liver toxicity and injury. Based on anamnestic, clinical, laboratory date of our patient, she was diagnosed Drug-induced hepatitis and started not typical therapy for Graves’ disease before surgery. Clinicians should maintain a high index of suspicion for underlying hyperthyroidism in patients presenting with unexplained liver dysfunction or unexplained jaundice.