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Fulminant Hepatic Failure Associated with Propylthiouracil

Chief, Department of Medicine, Hospital Carlos Van Buren, Valparaiso, Chile

Giorgio V Rossi, MD

Professor of Medicine, Faculty of Medicine, University of Valparaiso, Valparaiso

Humberto A Vallejos, MD

Chief, Department of Pathology, Hospital Carlos Van Buren

Rosemarie W Brenet, MD

Assistant Lecturer, Department of Medicine, Faculty of Medicine, University of Valparaiso

Isabel B Lopez, MD

Associate Lecturer, Department of Medicine, Faculty of Medicine, University of Valparaiso

Alfonso A Escribano, MD

Member, Department of Pathology, Hospital Carlos Van Buren

Reprints: not available.

OBJECTIVE: To report 2 fatal cases of fulminant hepatic failure associated with propylthiouracil treatment against hyperthyroidism.

CASE SUMMARY: Two women, 30 and 32 years old with no previous liver disease, were treated with propylthiouracil against Graves' disease. Both patients developed jaundice after a 4- and 5-month treatment period, respectively. The disease was similar to viral hepatitis, with a progressive course to severe liver dysfunction and death, along with multisystem organ failure despite extensive therapeutic measures. One of the patients was pregnant and subsequently miscarried. Neither patient had a history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. A submassive necrosis was shown in a postmortem histologic study.

DISCUSSION: Naranjo probability scale criteria applied to both cases confirm the adverse reactions as probable. These cases fit the requirements of drug hepatotoxicity proposed by Hanson and the Council of the International Organization of Medical Sciences. Eight deaths associated to propylthiouracil were found in our review of the medical literature up to December 2000.

CONCLUSIONS: Despite the widespread use of propylthiouracil, fulminant hepatitis with death is exceptionally rare; these 2 cases could be added to the fatal outcomes published to date.

Key Words: drug-induced hepatitis, fulminant hepatitis, hyperthyroidism, propylthiouracil

Published Online, January 13, 2003. www.theannals.com, DOI

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