MON-490 - Disrupted Adrenal Steroidogenesis with Abiraterone Therapy: Concurrent Mineralocorticoid Excess and Adrenal Insufficiency (AI)

Background: Abiraterone is a CYP17A1 inhibitor used in prostate cancer. It blocks 17-alpha hydroxylation of pregnenolone and progesterone which precede cortisol and androgen synthesis. The inhibition of cortisol synthesis leads to a compensatory rise in ACTH, and a mineralocorticoid excess syndrome which develops from a lack of concurrent long-acting glucocorticoid (GC) therapy.


Case: An 86-year-old man with metastatic prostate cancer, status post radical prostatectomy on leuprolide, abiraterone, and prednisone presented with acute encephalopathy. Initial evaluation was notable for blood pressure of 220/118 mmHg, temperature 100 F, white blood cell count 14,000, potassium 2.8, bicarb 28. Empiric antibiotics, acyclovir and Dexamethasone were started. Brain MRI revealed a small subacute infarct. Lumbar puncture was consistent with aseptic meningitis. Endocrinology was consulted for glucocorticoid stress dosing given the history of chronic steroid therapy, as well as severe hypertension in the context of incidental bilateral adrenal hyperplasia noted on CT scans done in the ED. The aldosterone level was elevated to 28.7 with a suppressed renin of 0.2. Subsequent history revealed that the patient was non adherent with prednisone. Abiraterone was discontinued after consultation with Oncology. Dexamethasone was stopped; stress doses of hydrocortisone were started and eventually converted to maintenance prednisone therapy for presumed primary AI due to CYP17A1 inhibitor use. He was referred to outpatient Endocrinology to monitor for recovery of cortisol synthesis. Hypertension and hypokalemia were successfully treated with spironolactone, a mineralocorticoid receptor antagonist.
The findings were felt to be consistent with Abiraterone-associated disruption of adrenal steroidogenesis.


Discussion: Abiraterone, a CYP17A1 inhibitor used in the treatment of metastatic prostate cancer, should be co-prescribed with a long-acting GC to prevent hypocortisolism, primary adrenal insufficiency, ACTH excess, and mineralocorticoid overproduction. The ACTH elevation not only aggravates mineralocorticoid excess but also leads to adrenal hyperplasia and/or nodularity. Despite a half-life of about 12 hours, the slow but tight binding of Abiraterone to CYP17A1 leads to prolonged inhibition lasting over a week. In the acute setting, glucocorticoids must be stress dosed, and hypertension must be controlled with a mineralocorticoid antagonist. In the long term, a more selective MRA will prevent the unwanted risk of androgen receptor agonism in the setting of prostate cancer. After abiraterone discontinuation, the HPA axis must be reassessed within 2 weeks. Long-term data is lacking.


Conclusion: Our case highlights the consequences of Abiraterone therapy in the absence of a long-acting GC; the need for patient education, and recommendations for appropriate management.

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