FRI523 A Case Of Acute Liver Failure Within 48 Hours Of Initiation Of High Dose Thionamides For Thyroid Storm

Abstract

Abstract Disclosure: L. Noor: None. J. Mullally: None. Thionamides, including methimazole and propylthiouracil, are medications used to treat hyperthyroidism and have rarely been associated with liver failure. Based on prior large retrospective studies, the onset of hepatotoxicity from thionamides occurs most commonly 4-12 weeks after ​​initiation, with the earliest cases occurring 7 days after initiation. We describe a case of very early onset acute liver failure within two days of initiation of high dose methimazole and PTU. A 43 year old female with past medical history of long-standing Graves’ disease and atrial fibrillation, presented to an outside hospital with upper respiratory symptoms and weight loss. On presentation, her vitals and physical examination were within normal limits. Initial labs showed normal LFTs, undetectable TSH, high FT3 6.75 pg/ml (n 2.0-4.4 pg/ml), high TT4 18 μg/dL (n 5.0-12.0 μg/dL) and PCR positive for COVID-19. She was started on methimazole 40 mg every 12 hours, beta-blocker, dexamethasone and remdesvir. The next day, she was found to be tachycardic, tachypneic with EKG showing atrial fibrillation with RVR and chest Xray showing flash pulmonary edema. She was intubated, methimazole was changed to PTU 200 mg every 4 hours and dexamethasone was changed to hydrocortisone 100 mg every 8 hours. An esmolol drip, potassium iodide and cholestyramine were started. She also received a single dose of intravenous amiodarone 300 mg for atrial fibrillation with RVR. The next day, labs showed new LFT abnormalities with AST 6647(n<35 U/L), ALT 1694 (n<55 U/L), ALP 132 (n<150 U/L), total bilirubin 8.4 (n<1.3 mg/dl). PTU was stopped and she was transferred to our hospital for liver transplant evaluation. On admission to our hospital, labs showed ALT 2728, AST 4930, ALP 180, T bilirubin 15.7, TSH 0.002, FT4 1.5 and TT3 29.6. She was started on hydrocortisone and propranolol. Viral and autoimmune hepatitis panel, acetaminophen and alcohol levels were negative. Abdominal ultrasound was unremarkable. Liver biopsy showed severe cholestatic hepatitis, perivenular necrosis and marked bile duct damage with neutrophilic inflammation, consistent with DILI. LFTs gradually improved over the following weeks. On hospital day 23, an uneventful total thyroidectomy was performed for definitive management of Graves’. We present a unique and rare case of acute liver failure within 48 hours of high dose methimazole and PTU administration for presumed thyroid storm. The patient recovered with gradual improvement in her LFTs and was successfully managed with total thyroidectomy. To our knowledge, this case represents the earliest onset of acute liver failure from thionamide use. Risk factors appear to include very high dose methimazole and PTU exposure as well as potentially the patient’s intermittent use of methimazole in the past. Further study is needed to clarify potential risk factors of thionamide-induced hepatotoxicity as data is limited. Presentation: Friday, June 16, 2023