MON-501 - Blocking More than Just Androgens: Abiraterone and Adrenal Crisis

Abiraterone, a cancer drug approved in 2011 for metastatic castration resistant prostate cancer, selectively inhibits action of 17 hydroxylase enzyme (CYP17A1) in steroidogenesis to prevent the production of androgens. Through its mechanism, it limits the action of both 17-alphahydroxylase and 17,20 lyase enzymes, leading to relative cortisol deficiency and potential for mineralocorticoid excess. Prednisone is used concurrently to prevent adrenal insufficiency and mitigate upregulation of ACTH, which in turn prevents hyperaldosteronism. We present a patient with suspected adrenal crises and concurrent mineralocorticoid excess while on abiraterone and prednisone therapy, likely from inadequate dosing during stress. We also address the duration of iatrogenic hypocortisolism, after discontinuation of abiraterone.

An 81-year-old male, treated with Abiraterone 250mg and prednisone 5 mg daily for metastatic prostate cancer for about 4 months, was admitted to the hospital for 5 mm subdural hematoma after a mechanical fall. He reported compliance with medications. Five days prior to admission, he was diagnosed with influenza and reported fever and progressive fatigue. On admission, vital signs were stable with no hypotension or tachycardia. Laboratory evaluation revealed hyponatremia (sodium 129 mmol/l, normal 135 - 145 mmol/l), hypokalemia (potassium 2.5 mmol/l, normal 3.5 – 5.2 mmol/l ), metabolic alkalosis (bicarbonate 31 mmol/l, normal 21 – 29 mmol/l), but no hypoglycemia. His ACTH was elevated at 128 pg/mL (normal 7.2 – 63.3 pg/mL). The patient was diagnosed with adrenal crisis in the setting of recent influenza and subdural hematoma with simultaneous mineralocorticoid excess from ACTH upregulation. He was treated with stress dose prednisone (15 mg daily). Over four days, patient's mental status improved with improvement in labs (ACTH 63 pg/mL, sodium 135 mmol/L, potassium 4mmol/l). Abiraterone was stopped and patient was discharged home on prednisone 5 mg daily for 2 weeks. Cosyntropin stimulation test done after holding prednisone for 3 days was abnormal (post cosyntropin cortisol 7.3 mcg/dl, normal >14 mcg/dl). Glucocorticoids were switched to hydrocortisone 15mg in the morning and 5mg in the afternoon for 1 month. Cosyntropin stimulation test repeated after holding hydrocortisone for 3 days, was normal (post cosyntropin cortisol 18.7 mcg/dl). Hydrocortisone was then tapered by 5 mg over 9 days.

This case highlights that adrenal crisis may occur during a stressful event despite using prednisone with abiraterone. Diagnosis may be delayed due to mixed symptoms of cortisol deficiency and mineralocorticoid excess. Thus, patients should still be treated with stress dose glucocorticoids. We also suggest that patients may require glucocorticoid replacement for several weeks after discontinuation of abiraterone due to persistent hypocortisolism.

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