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Abstract: TH-PO365

Abiraterone-Induced Hypokalemia Refractory to Exogenous Glucocorticoids Successfully Managed with Amiloride

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Nombera, Natalia R., Universidad Peruana Cayetano Heredia, Lima, Lima, Peru
  • Velez, Juan Carlos Q., UQ-Ochsner Clinical School, Brisbane, Queensland, Australia

Group or Team Name

  • Ochsner Group.
Introduction

Abiraterone acetate irreversibly inhibits CYP17 blocking androgen synthesis in tumors, testes, and adrenal glands, and is used for prostate cancer treatment. Diversion of this enzymatic pathway leads to increased production of the mineralocorticoid molecules deoxycorticosterone and corticosterone. By virtue of its enzymatic blockade, abiraterone also decreases cortisol, leading to a compensatory rise in ACTH and further rise in mineralocorticoid production, leading to hypokalemia. These effects can be mitigated by ACTH suppression with prednisone. Herein, we report an unusual case of abiraterone-induced hypokalemia despite glucocorticosteroid coadministration, successfully managed with amiloride.

Case Description

A 70-year-old man with prostate cancer receiving chronic treatment with abiraterone and prednisone, presented with dyspnea, emesis and low back pain. He had recently undergone bronchoscopy due to an abnormal CT scan concerning for a granulomatous lesion. Review of old records revealed several episodes of serum potassium (K) of 2.5 – 3.0 mEq/L for the last 3 years. On arrival, blood pressure was 173/107 mmHg, pulse 109/min. Physical exam was normal. Pertinent serum laboratory data revealed a K level of 2.5 mEq/L, sodium 145 mEq/L, creatinine (Cr) 0.8 mg/dL, and carbon dioxide 20 mEq/L. Despite aggressive oral and intravenous KCl supplementation, hypokalemia persisted. Urine K-to-Cr ratio was 82 mEq/g. Plasma renin activity was 0.6 ng/mL/hr and plasma aldosterone concentration was 21 ng/dL. ACTH was 56 pg/mL (normal range 0-46). Corticosterone level was obtained: 6190 ng/dL (normal range 53-1560). A diagnosis of glucocorticoid-refractory abiraterone-induced hypokalemia was made.

Discussion

Amiloride was initiated, and aggressive repletion of potassium was continued. After discussion with Oncology, abiraterone was discontinued. Serum K normalized to 4.0 mEq/L in 2 days and remained normal 2 weeks post-discharge. Amiloride was discontinued and serum K remained normal therafter. This case exemplifies how abiraterone can lead to severe symptomatic hypokalemia despite chronic glococorticoidsteroid mitigating therapy. Elevated ACTH and corticosterone levels confirm the diagnosis. Direct blockade of the epithelial sodium channel (EnaC) with amiloride is an effective therapy.