ODP322 Impact of Mifepristone on Liver Function and Resolution of Liver Steatosis in Patients with Cushing Syndrome – A Case Study

BACKGROUND: Hypercortisolism is a recognized cause of non-alcoholic fatty liver disease (NAFLD). Mifepristone (Korlym®, Corcept Therapeutics), a glucocorticoid receptor (GR) antagonist, is FDA-approved for the treatment of hyperglycemia in patients with endogenous Cushing syndrome (CS). Mifepristone has also shown beneficial effects in preclinical models of fatty liver disease, including reduced liver injury, improved insulin sensitivity, and increased plasma adiponectin concentrations. Here, we report the case of a patient with CS and liver steatosis who was treated intermittently with mifepristone. CLINICAL CASE: A 36-year-old woman with CS associated with uncontrolled type 2 diabetes mellitus, obesity, major depressive disorder, hyperlipidemia, hypertension, and liver steatosis was intermittently treated with mifepristone for 3 years. Abdominal imaging was performed several times for abdominal pain. Before treatment with mifepristone was initiated, the patient had a body weight of 198 lbs, BMI of 32kg/m 2, HbA1c of 11.5%, and liver steatosis as noted on abdominal imaging with normal liver function tests (ALT: 40 U/L [normal: 6-42 U/L], AST: 30 U/L [normal: 8-36 U/L]). After 16 months, treatment with mifepristone was discontinued secondary to abnormal uterine bleeding. Imaging performed around the time of discontinuation showed resolution of liver steatosis, which was accompanied by significant reductions in LFTs to levels typically seen in healthy volunteers without liver steatosis (ALT: 10 U/L, AST: 17 U/L). The patient's HbA1c had decreased to 6.8%. Imaging performed 7months after mifepristone discontinuation showed recurrence of liver steatosis, LFTs had returned to pre-treatment values (ALT: 42 U/L, AST: 31U/L), and HbA1c had increased to 9.3%. The patient underwent hysterectomy and restarted mifepristone treatment. One year after resumption of mifepristone, imaging showed that liver steatosis had resolved once again, along with a similar reduction in LFTs as observed before (ALT: 16 U/L, AST: 12 U/L). Fourteen months after restart, mifepristone was discontinued again. Labs and imaging performed 10 months after discontinuation showed, as previously, recurrence of liver steatosis along with elevated LFTs (ALT: 100 U/L, AST: 56 U/L). Data from mifepristone's prospective pivotal study (SEISMIC, NCT00569582) of 50 patients with CS also showed a similar reduction in ALT throughout the study, which was reversed during the 6-week discontinuation follow-up phase of the study. This was followed by a repeat reduction when mifepristone was restarted in the extension study (NCT00936741). CONCLUSION: These results suggest that mifepristone is effective in improving liver function and decreasing liver steatosis in patients with endogenous CS, a trend that is also accompanied by improvement in insulin resistance and glycemic control. Presentation: No date and time listed