How Low Can You Go? Abiraterone-Mediated Mineralocorticoid Excess Despite Prednisone Use

Introduction: Abiraterone is approved for the treatment of castration-resistant prostate cancer by inhibiting androgen synthesis. Through this mechanism, however, it also leads to decreased Cortisol synthesis and increased ACTH production. If not given with sufficient dose of oral steroids, this can lead to ACTH mediated mineralocorticoid excess (AME). We present a case of Abiraterone-Induced AME despite glucocorticoid use. Case Description: 71-year-old male with prostate cancer, presenting with 4 weeks of weakness, and myalgia. Evaluation showed profound hypokalemia with potassium of 1.6 mEq/L and Rhabdomyolysis with a CK level of 7700 U/L, creatinine remained normal. He also had resistant hypertension despite being on multiple oral agents. Further testing suggested potassium wasting with a potassium/Creatinine ratio of 58 mmol/g. Aldosterone level was at less than the detectable range and Renin levels low suggesting a diagnosis of Abiraterone-Induced AME. Abiraterone was discontinued and he was started on Eplerenone with oral potassium supplementation leading to resolution of hypokalemia and hypertension. Discussion: Profound hypokalemia can lead to life threatening complications, and it is imperative for nephrologists to recognize the presence of AME picture and identify potential rare causes. Abiraterone suppresses androgen production by inhibiting CYP17A1 enzyme. This enzyme is also key in cortisol production pathway. Decreased cortisol levels can lead to increased ACTH secretion causing an increase in Deoxycorticosterone which is a potent mineralocorticoid itself. This leasds to the clinical picture of hypertension, metabolic alkalosis, and hypokalemia. Oral Prednisone is used to suppress ACTH and prevent AME. Close monitoring of potassium levels while on Abiraterone is needed and will likely lead to early identification and need for treatment. However, our case highlights the need for the addition of mineralocorticoid receptor blocker such as Eplerenone to the Prednisone to fully prevent this complication.This case sheds light on Abiraterone as a rare yet significant cause of AME and the need for further investigation of the effective therapy to prevent Abiraterone induced AME.