Two Cases of Severe Clinical and Histologic Hepatotoxicity Associated with Troglitazone
Authors: Norman Gitlin
Journal: Annals of Internal Medicine (1998)

Brief Communications1 July 1998Two Cases of Severe Clinical and Histologic Hepatotoxicity Associated with TroglitazoneNorman Gitlin, MD, Neil L. Julie, MD, Charles L. Spurr, MD, Kie N. Lim, MD, and Herbert M. Juarbe, MDNorman Gitlin, MDFrom Emory University School of Medicine and Shady Grove Adventist Hospital, Atlanta, Georgia., Neil L. Julie, MDFrom Emory University School of Medicine and Shady Grove Adventist Hospital, Atlanta, Georgia., Charles L. Spurr, MDFrom Emory University School of Medicine and Shady Grove Adventist Hospital, Atlanta, Georgia., Kie N. Lim, MDFrom Emory University School of Medicine and Shady Grove Adventist Hospital, Atlanta, Georgia., and Herbert M. Juarbe, MDFrom Emory University School of Medicine and Shady Grove Adventist Hospital, Atlanta, Georgia.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-1-199807010-00008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Several oral antihyperglycemic agents are available for management of type 2 diabetes. These agents generally fall into the chemical or function groups sulfonylureas, biguanides, or α-glucosidase inhibitors. Recently, the U.S. Food and Drug Administration approved troglitazone (Rezulin, Parke-Davis, Morris Plains, New Jersey), a thiazolidinedione agent that is unrelated to the aforementioned categories, as a novel oral antihyperglycemic agent. It decreases hepatic glucose output and increases insulin-dependent glucose metabolism in skeletal muscle [1, 2]. It is not an insulin secretagogue. We report two patients who had severe hepatotoxicity associated with troglitazone administration.Patient 1A 44-year-old woman with a history of ...References1. Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med. 1994; 331:1188-93. Google Scholar2. Kumar S, Boulton AJ, Beck-Nielsen H, Berthezene F, Muggeo M, Persson B, et al. Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone Study Group. Diabetologia. 1996; 39:701-9. Google Scholar3. Lee WM. Review article: drug-induced hepatotoxicity. Aliment Pharmacol Ther. 1993; 7:477-85. Google Scholar4. Farrell GC. Drug-induced Liver Disease. London: Churchill Livingstone; 1994:247-300. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Emory University School of Medicine and Shady Grove Adventist Hospital, Atlanta, Georgia.Corresponding Author: Norman Gitlin, MD, Emory University School of Medicine, Division of Digestive Diseases, WMB 2101, Pierce Drive, Atlanta, GA 30322.Current Author Addresses: Drs. Gitlin and Lin: Emory University School of Medicine, Division of Digestive Diseases, WMB 2101, Pierce Drive, Atlanta, GA 30322. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTroglitazone-Induced Hepatic Failure Leading to Liver Transplantation: A Case Report Brent A. Neuschwander-Tetri , William L. Isley , Julie C. Oki , Sanjay Ramrakhiani , Stella G. Quiason , Nancy J. Phillips , and Elizabeth M. 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Nierenberg, MDDifferentiating members of the thiazolidinedione class: a focus on safetyType 2 diabetes management: A comprehensive clinical review of oral medicationsEffects of Pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: A retrospective review of randomly selected medical recordsEffects of the Thiazolidinediones on Cardiovascular Risk FactorsHepatotoxicity of thiazolidinedionesPioglitazone Improves Left Ventricular Diastolic Function and Decreases Collagen Accumulation in Prediabetic Stage of a Type II Diabetic RatEnzyme-Induction Dependent Bioactivation of Troglitazone and Troglitazone Quinone In VivoOral agents for the treatment of type 2 diabetes mellitus: Pharmacology, toxicity, and treatmentSevere Cholestatic Hepatitis From Troglitazone in a Patient With Nonalcoholic Steatohepatitis and Diabetes MellitusA Pilot Study of A Thiazolidinedione, Troglitazone, in Nonalcoholic SteatohepatitisFactors Associated with the Risk of Liver Enzyme Elevation in Patients with Type 2 Diabetes Treated with a ThiazolidinedioneNonhypoglycemic Effects of ThiazolidinedionesAkhil A. Parulkar, MD, Merri L. Pendergrass, MD, PhD, Ramona Granda-Ayala, MD, Tri Richard Lee, MD, and Vivian A. Fonseca, MDStudies on the Metabolism of Troglitazone to Reactive Intermediates in Vitro and in Vivo. Evidence for Novel Biotransformation Pathways Involving Quinone Methide Formation and Thiazolidinedione Ring ScissionAssessing causality in drug-induced liver injuryPathophysiology and Pharmacological Treatment of Insulin Resistance*Troglitazone-Associated Hepatotoxicity Treated Successfully with SteroidsKathleen A. Prendergast, MD, Carl L. Berg, MD, and Ralph Wisniewski, MDOral medications for treating diabetes mellitus in dogs and catsTroglitazone prevents fatty changes of the liver in obese diabetic ratsEfficacy and Safety of Troglitazone in the Treatment of Lipodystrophy SyndromesElif Arioglu, MD, Jennifer Duncan-Morin, RN, Nancy Sebring, RD, Kristina I. Rother, MD, Nicole Gottlieb, BA, Jay Lieberman, BS, David Herion, MD, David E. 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Misbin, MDSevere Hepatotoxicity Associated with TroglitazoneSteven K. Herrine, MD and Cuckoo Choudhary, MDInsulin, glucagon, and hypoglycemic drugsMechanisms by which Thiazolidinediones Enhance Insulin ActionInhibition of Cytochrome P450 Enzymes 1 July 1998Volume 129, Issue 1Page: 36-38KeywordsBilirubinBiopsyFibrosisHepatitis AHepatocytesHepatotoxinsInsulinLiverNecrosisProthrombin time Issue Published: 1 July 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...