Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature

Abstract

Drug-induced liver injury (DILI) is one of the leading causes of death from acute liver failure (ALF) in the United States, accounting for approximately 13% of ALF cases in the United States. Selective androgen receptor modulators (SARMs) were first developed to increase muscle mass while avoiding the side effects of conventional androgenic steroids. Although not Food and Drug Administration (FDA) approved, they are widely available online and are consumed to enhance athletic performance. We report a 22-year-old, previously healthy male, who presented with a two-week history of worsening jaundice, nausea, fatigue, pruritus, dark urine, and light stools. He reported taking the SARM, RAD-140, for 16 weeks. Examination showed scleral icterus. The liver panel showed alkaline phosphatase (ALP) 5.3 µkat/L, alanine transaminase (ALT) 1.66 µkat/L, aspartate transaminase (AST) 1.18 µkat/L, direct bilirubin 294 µmol/L, total bilirubin 427.5 µmol/L, and international normalized ratio (INR) 0.9. Viral hepatitis and autoimmune panel were unremarkable. Alpha-1 antitrypsin and ceruloplasmin levels were within normal limits. Bile sludge was seen on ultrasound. Magnetic resonance cholangiopancreatography (MRCP) abdomen showed segmental narrowing of the intrahepatic ducts. Endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. Liver biopsy showed mixed portal hepatitis, cholestasis, and biliary reactive changes with ceroid-loaded macrophages; a picture consistent with DILI. The patient was treated supportively and discharged with scheduled hepatology follow-up. At the one-month follow-up, his total bilirubin had fallen from a peak of 530 mol/L to 188 mol/L. The diagnosis of DILI can be made based on the timing of exposure and the exclusion of other etiologies. Liver enzymes normalized three to 12 months after product discontinuation. We hope this report will remind primary care physicians of the potential hepatotoxic side effects of muscle-building compounds and encourage them to report suspected DILI to the FDA using the MedWatch system.

Drug‐induced liver injury from selective androgen receptor modulators, anabolic‐androgenic steroids and bodybuilding supplements in Australia

“…Three patients in our series had testing of the SARM used which confirmed the presence of the labelled SARM and in one product there was an additional SARM identified. Less than 20 cases of DILI due to SARMs have been reported in the literature since 2020 involving ligandrol (LGD‐4033), testolone (RAD‐140), ostarine (enobosarm) and YK‐11 6–9,16,17 . We found a similar demographic of patients with DILI due to SARMs, namely all males, aged 24–46 years (other cases were 19–52 years).…”

“…Less than 20 cases of DILI due to SARMs have been reported in the literature since 2020 involving ligandrol (LGD-4033), testolone (RAD-140), ostarine (enobosarm) and YK-11. [6][7][8][9]16,17 We found a similar demographic of patients with DILI due to SARMs, namely all males, aged 24-46 years (other cases were 19-52 years). We found 86% to be symptomatic, whereas all previously reported cases were.…”

Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases

“…peak 73 IU/L); TB 0.8 mg/dL Negative No No medical history Not mentioned Arayangkool et al [ 46 ] LGD-4033 Ostarine RAD-140 Jaundice Pruritus Weight loss Abdominal pain Cholestatic liver injury Canalicular bile plugs Hepatocellular dropout Acute tubular injury with pigmented bile casts 8 weeks No AST 52 IU/L ALT 52 IU/L ALP 343 IU/L TB 43.3 mg/dL Negative No No medical history Analytical testing for SARMS not performed. Dose was not specified Reported biopsy Ladna et al [ 47 ] RAD-140 Nausea, vomiting, severe right upper quadrant abdominal pain, jaundice, dark urine, constipation Acute liver injury 8 weeks No AST 51 IU/L ALT 243 IU/L TB 4.9 mg/dL Negative No No medical history Analytical testing for SARMS not performed Mohamed et al [ 48 ] RAD-140 Jaundice, nausea, fatigue, dark urine, acholic light gray-colored stool, pruritus Mixed portal hepatitis, cholestasis, biliary reactive changes 16 weeks Performance-enhancing supplement AST 70.8 IU/L (1.18 µkat/L) ALT 99.6 IU/L (1.66 µkat/L) ALP 318 IU/L (5.3 µkat/L) TB 427.5 mg/dL Negative No No medical history Analytical testing for SARMS not performed. Dose was not specified Reported biopsy Cardaci et al [ 49 ] LGD-4033 10 mg daily Controlled study—not reported Controlled study—not reported 5 weeks …”

Bile Cast Nephropathy Because of Acute Liver Injury Associated With Selective Androgen Receptor Modulators

“…The duration of SARM use in reported cases ranged from 2 to 12 weeks before developing symptoms, which was consistent with our patient who took them for 2 months. 3 Given that cholestatic liver injury patterns have been reported as a characteristic of SARM-associated DILI, 4 providers and athletes need to recognize the danger of SARMs, which include the potential to cause liver and kidney injury.…”