Enzalutamide Endocrine Effects — RACP Adult Medicine MCQ

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HardMedical OncologyEnzalutamide Endocrine EffectsRACP Adult Medicine

A 72-year-old man with prostate cancer on enzalutamide develops hypertension and fatigue. His cortisol level is 650 nmol/L at 9 AM (normal). His renin is suppressed and aldosterone is low. What additional hormonal test should be performed?

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Correct answer: B — Deoxycorticosterone (DOC) level

Enzalutamide is a CYP17A1 inducer (unlike abiraterone which is a CYP17A1 inhibitor). While less commonly recognised than abiraterone's mineralocorticoid excess, enzalutamide can cause adrenal insufficiency through CYP enzyme effects. The hypertension, suppressed renin, and low aldosterone in this case may suggest accumulation of other mineralocorticoid precursors or an alternative mechanism. Deoxycorticosterone (DOC) levels can be elevated in patients on agents affecting the steroid synthesis pathway. More practically, the fatigue may represent enzalutamide-related adverse effects (experienced by ~30% of patients) and adrenal axis evaluation including cortisol day curve and ACTH testing is appropriate.

Reference: AMH – 2025 – Enzalutamide; eTG – 2025 – Endocrinology