MON-305 What a MES!: A Case of Abiraterone-induced Mineralocorticoid Excess Syndrome

Abstract Disclosure: C.M. Fabros: None. M.Y. Tanchee: None. Metastatic castration-sensitive prostate cancer (mCSPC) poses a significant therapeutic challenge, requiring strategies that enhance survival and delay disease progression. Adding abiraterone acetate and prednisone to androgen-deprivation therapy (ADT) significantly enhances outcomes. Abiraterone, a selective CYP17A1 inhibitor, suppresses androgen biosynthesis, slowing disease progression. However, its dual inhibition of 17α-hydroxylase and 17,20-lyase can lead to adverse effects from cortisol suppression.A 79-year-old male with prostate carcinoma and bone metastases on Triptorelin pamoate every six months and abiraterone 250 mg twice daily with prednisone 5 mg once daily for over a year has hypertension with more than three anti-hypertensive medications, including a diuretic, and also has diabetes with chronic kidney disease. He presented with a two-week history of progressive weakness and dizziness. On admission, blood pressure was 200/100 mmHg, requiring IV nicardipine with persistent hypokalemia despite IV and oral potassium replacement. Further evaluation revealed renal potassium loss, metabolic alkalosis, low serum cortisol, and high ACTH, consistent with abiraterone-induced mineralocorticoid excess syndrome (MES). A normal aldosterone-renin ratio ruled out primary aldosteronism. Abiraterone was discontinued, and prednisone was switched to dexamethasone due to its lack of mineralocorticoid activity. As amiloride was unavailable, finerenone, a selective mineralocorticoid receptor antagonist, was initiated.Abiraterone inhibits CYP17A1, reducing cortisol production by blocking 17α-hydroxylase and suppressing androgen synthesis, key for prostate cancer progression. Subsequently, ACTH increases leading to excess mineralocorticoid production. Elevated 11-deoxycorticosterone and corticosterone promote salt reabsorption and potassium excretion, causing hypertension and hypokalemia. Glucocorticoid aims to counteract the loss of negative feedback on ACTH, thereby reducing the onset and severity of MES. Mineralocorticoid antagonists such as spironolactone suppress residual activity in these patients but may induce androgen receptor mutations, leading to potential treatment resistance. In contrast, amiloride, an ENaC inhibitor, manages mineralocorticoid excess in these patients without interfering with abiraterone's anti-cancer effects. Finerenone, a novel, selective MRA, is as effective as spironolactone with fewer side effects and better cardiovascular outcomes, particularly in CKD with diabetes.The treatment for this case effectively resolved MES, stabilizing potassium levels and controlling blood pressure. This case highlights the importance of early recognition and management of abiraterone-induced MES. Standardized treatment guidelines are crucial for improving outcomes and reducing complications. Presentation: Monday, July 14, 2025