Mifepristone induced liver injury in a patient with Cushing syndrome: a case report and review of the literature

Abstract

Background: Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids. Case presentation: Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient’s symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality. Conclusions: Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.