Severe Liver Dysfunction Within 48 Hours of Thionamide Therapy in Thyrotoxicosis: A Case Report

BACKGROUND Thionamides, including methimazole and propylthiouracil, are medications used to treat hyperthyroidism and have rarely been associated with liver failure. We present a case of fulminant liver failure within 2 days of initiation of high-dose methimazole and propylthiouracil. CASE REPORT A middle-aged woman with Graves disease was found to have biochemical hyperthyroidism and SARS-CoV-2 infection. She was started on methimazole, metoprolol, dexamethasone, and remdesivir. On hospital day 2, she developed atrial fibrillation with rapid ventricular response and flash pulmonary edema, requiring intubation. Methimazole was switched to propylthiouracil. On hospital day 3, severe elevations in aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels were noted. Propylthiouracil was held, and liver biopsy demonstrated findings consistent with drug-induced liver injury. Liver function tests gradually improved over the subsequent weeks, with supportive measures. Once stabilized, the patient underwent a successful and uneventful total thyroidectomy and ultimately recovered fully. Most notable in our patient was the rapid onset of fulminant liver failure within 48 h of thionamide initiation, a finding that has yet to be reported elsewhere. CONCLUSIONS This case demonstrates an earlier timeframe for liver injury from thionamide use than is typically expected. Risk factors may include high-dose methimazole and propylthiouracil exposure as well as concurrent SARS-CoV-2 infection and brief treatment with remdesivir.