Endocrine Abstracts

Background: Enzalutamide is a next-generation androgen receptor (AR) antagonist, used as a daily oral agent, in the treatment of castration-resistant prostate cancer. Its suppression of 11β-hydroxysteroid dehydrogenase-2 enzyme has been reported in the literature, leading to hypertension through a relative increase in cortisol concentration at the level of the mineralocorticoid receptors. Enzalutamide is also known to be a potent inducer of drug metabolising enzymes (cytochrome P450 isoenzyme 3A4). To our knowledge, its clinical effect on cortisol dynamics has not been previously reported. We report a case of altered glucocorticoid dynamics and false positive dexamethasone suppression test result in a patient on Enzalutamide.

Case: A 74-year-old male, with previous acromegaly secondary to a pituitary microadenoma, attended for routine clinical review. He remained in remission 11 years post pituitary surgery. He was recently diagnosed with metastatic prostate cancer and received radical radiotherapy. Soon after commencing Enzalutamide he developed hypertension and his diabetes control deteriorated. On examination he had increased abdominal adiposity but no other cushingoid features. After a low dose dexamethasone suppression test (LDDST) his cortisol remained unsuppressed at 181 nmol/l. His baseline ACTH was elevated at 148ng/l. A 24 hour urine cortisol (GC-MS) was normal at 112 nmol/day. His midnight and early morning salivary cortisol were within normal reference ranges. Untimed spot urine collection revealed relatively high cortisol metabolite concentrations on steroid profiling. These abnormal results were felt to be strongly associated with induction of steroid metabolising enzymes by Enzalutamide. The drug was withheld for 3 weeks on advice from the oncology team and a repeat LDDST revealed normal suppression of cortisol to <20 nmol/l.

Conclusion: Enzalutamide, a potent CYP3A4 enzyme inducer, can alter glucocorticoid metabolism in vivo. Clinicians need to be aware of abnormal steroid dynamics and false positive dexamethasone suppression test results in patients on Enzalutamide.