Propylthiouracil-Induced Hepatotoxicity: A Case Report

Abstract

Purpose: Case Presentation: A 61-year-old Hispanic male with a history of Graves Disease and CHF presented with three days of diffuse abdominal pain, localized to the epigastric and periumbilical areas. History revealed the patient had been taking propylthiouracil (PTU) for five months with no prior known toxicity. Exam revealed jaundice and voluntary guarding without rebound. There was no hepatosplenomegaly, ascites, or palpable masses. Labs revealed elevated total bilirubin, lactic acid, PT (39.7), INR (4.02), LDH, and markedly elevated AST (2054 U/L), ALT (1697 U/L). Other major causes of transaminitis, such as acetominophen toxicity, viral hepatitis, and ischemic livery injury were ruled out. Abdominal imaging demonstrated a heterogeneous liver with moderate ascites. Transaminases peaked >5000 U/L after 3 days. The patient symptomatically improved with correction of his liver enzymes and coagulopathy through supportive care and discontinuation of PTU. Discussion: Propylthiouracil is a thiocarbamide used in the treatment of hyperthyroidism, Graves' disease, and multinodular goiter. On rare occasions, PTU can induce serious hepatotoxicity, although a transient increase in aminotransferases has been observed within the first week of treatment in up to 28% of patients 3, 5, 6. In this vignette, we present a case of PTU-induced hepatitis with unusually high liver enzymes. PTU-induced hepatitis was diagnosed based on the occurrence of liver damage within a few months of initiation of therapy, the absence of significantly elevated liver enzymes prior to therapy, and subsequent recovery after discontinuation of the drug. Our patient's condition was complicated by congestive heart failure. Elevated central venous pressure is transmitted to the liver, which can lead to accumulation of deoxygenated blood, hepatocellular hypoxia, necrosis, and fibrosis over time. In such a setting, glucuronidation-dependent metabolism of PTU is compromised. The estimated incidence of antithyroid drug-associated hepatotoxicity is less than 0.5%. PTU-induced hepatitis should be prevented because mortality rate can be as high as 25% due to complications of liver failure 7. Monitoring of liver function and liver transaminases may not necessarily identify those patients who will eventually develop PTU-induced liver failure because it can occur suddenly and be rapidly progressive. This case demonstrates the importance of recognizing such a serious complication in a commonly prescribed medication.