S2718 Harmful Gains: Drug-Induced Liver Injury From Selective Androgen Receptor Modulators

Abstract

INTRODUCTION: Hepatotoxicity associated with androgenic anabolic steroids (AASs) is well-recognized. Selective androgen receptor modulators (SARMs) such as RAD-140 (Testolone) are a novel class of agents being marketed by some supplement manufacturers as “legal steroids” that carry the advantage of androgen receptor specificity, tissue selectivity and lack of undesired AAS side effects. Data on the association of SARMs with drug-induced liver injury (DILI) is limited. Here, we present a rare case of drug-induced liver due to SARM use. CASE DESCRIPTION/METHODS: A 31-year-old male with asthma presented with 3 days of epigastric pain, jaundice and pruritis. He reported using a SARM supplement (RAD-140) for 12 weeks prior to admission. He denied alcohol use. Vital signs were normal. Physical exam was notable for scleral icterus and jaundice without other stigmata of chronic liver disease. Admission labs showed total bilirubin 8.4 mg/dL (unconjugated 2.1,conjugated), alkaline phosphatase 122 mg/dL, ALT 293 mg/dL, AST 145 mg/dL. Work-up for causes of liver injury including viral hepatitis, Wilson’s disease, hemochromatosis, autoimmune hepatitis and alpha-1-antitrypsin was unremarkable. MRI abdomen showed normal liver parenchyma, patent portal and splenic vasculature, no ductal dilatation or cholelithiasis. The cause of liver injury was thought to be SARM use. His pruritis was treated with cholestyramine. The bilirubin peaked at 20.3 mg/dL on day 15 and trended down on repeat labs 1 month after admission to 15.1 mg/dL. DISCUSSION: Despite FDA-issued public advisories regarding safety concerns associated with SARMs, they continue to be promoted for use particularly as a body building supplement. While the reported tissue selectivity of SARMs can be promising for therapeutic use in hormonal and age-related disorders, this case among others brings the aspect of tissue selectivity into question. Cases of SARM-related DILI are likely underreported and underrecognized. SARMs are thought to activate the intracellular androgen receptor that influences transcription of genes that result in androgen-stimulated cell growth. As such, they are thought to have similar consequences as AAS, which results in three types of liver injury related to augmented cell growth: peliosis hepatis, hepatic tumors and nodular regenerative hyperplasia. As SARM use becomes more prevalent, it is crucial to report these cases for earlier identification and offending agent cessation and for a better understanding of long-term consequences.