Acute Cholestatic Liver Disease Secondary to Propylthiouracil and Hyperthyroid Cardiomyopathy in Patient with Graveʼs Disease

Abstract

Purpose: A 45-year-old female with history of hypertension, hyperthyroidism came for the evaluation of generalized weakness, sweating, loss of appetite, and pruritic rash for five days. Patient had no history of other pharmaceutical or herbal medication use, infections, and abuse of alcohol or contact with toxic substances or substance abuse. On admission, patient was tachycardic and physical examination was unremarkable except patient looks icteric and papular urticarial rash all over the body. Liver function were unremarkable six weeks prior to admission when patient was admitted with decompensated systolic heart failure and found to have hyperthyroidism. Patient was then started with PTU and regimens for heart failure (aspirin, carvedilol, enalapril, furosemide and digoxin). Liver chemistry showed total bilirubin 7.8 mg/dl, direct bilirubin 6.0 mg/dl, alkaline phosphatase 595 U/L, AST 154 U/L, ALT 174 U/L; INR was 1.6; TSH and FT4 were 0.0260 and 4.36 ng/dL uU/mL respectively, and antiTPO was 89.5 IU/mL. Renal function was normal.USG of liver and gall bladder showed hepatomegaly and nondistended gall bladder without cholelithiasis. Viral, metabolic and autoimmune liver diseases were excluded and liver biopsy results showed drug-induced chronic hepatitis. During the hospital course, PTU was discontinued and patient was started with potassium iodide. Liver function tests were significantly improved to baseline in a few weeks, later patient did not follow-up in the clinic and patient has compliance issues taking her potassium iodide, presented after few weeks with severe heart failure due to cardiomyopathy and acute liver failure due to ischemic hepatitis. PTU related liver toxicity is likely to occur in about 1% of treated patients. Our case report re-emphasizes to acknowledge the severe acute cholestatic liver disease with the use of PTU in the setting of cardiomyopathy due to hyperthyroidism, and need of regular interval follow up of the patient including the liver function test. The duration of optimal biochemical follow up requires large randomized prospective study but should be at least six months during which highest incidence of liver injury has been noticed in several studies.