Abstract: PO1848
Abiraterone-Induced Mineralocorticoid Excess Despite Concurrent Prednisone in Setting of Drug-Induced Liver Injury(DILI)
Session Information
- Cancer and Kidney Diseases: Nephrotoxins, RCC, and More
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Nakhoul, Georges, Cleveland Clinic, Cleveland, Ohio, United States
- Nino, Jessica, Cleveland Clinic, Cleveland, Ohio, United States
- Tan, Xin Yee, Cleveland Clinic, Cleveland, Ohio, United States
- Mehdi, Ali, Cleveland Clinic, Cleveland, Ohio, United States
- Shingarev, Roman A., Cleveland Clinic, Cleveland, Ohio, United States
Introduction
Abiraterone,a CYP17A inhibitor used in the treatment of castration-resistant prostate cancer(CRPC),is prescribed with concurrent glucocorticoids(GC) to prevent secondary mineralocorticoid excess(SME).We hereby describe a case of refractory hypokalemia in setting of abiraterone-induced SME despite prophylactic GC.
Case Description
A 70-year-old male with CRPC on abiraterone 1g and prednisone 5mg daily,presented with jaundice,fatigue and hypertension.Workup revealed hyperbilirubinemia,transaminitis and profound hypokalemia.Liver biopsy demonstrated DILI.Abiraterone was thus discontinued.Hypokalemia persisted despite aggressive repletion with up to 320mEq KCl daily.Deoxycorticosterone elevation confirmed abiraterone-induced SME.Increased dosage of prednisone to 40mg daily and addition of eplerenone led to prompt normalization of potassium and blood pressure.Darolutamide was started after DILI resolution for CRPC treatment.
Discussion
Abiraterone’s antitumor effect lies in reduction of androgen production by CYP17 inhibition.Excessive deoxycorticosterone/corticosterone accumulation,driven by reactive rise in corticotropin,may manifest as hypokalemia,hypertension or fluid retention.GC coadministration serves to mitigate SME.SME in this case may be explained by:1)Liver injury:Pharmacokinetic studies have shown increased systemic abiraterone exposure in liver impairment up to 3.6 folds,necessitating dose reduction or drug discontinuation.Severe liver impairment causing decreased availability of hepatic 11β-HSD1 may also drive down conversion of prednisone into its active form prednisolone,removing negative feedback to corticotropin.2)Prednisone 5mg BID or dexamethasone 0.5mg daily has shown superiority to prednisone 5mg daily(in this case)for SME prevention,at expense of greater weight gain and insulin resistance.Eplerenone can be used in addition to GC in SME treatment and may be noninferior to GC as steroid sparing preventive option.Spironolactone should be avoided due to its affinity to androgen receptor.It is prudent to monitor for medication adjustment as SME resolves.