Endocrine Abstracts

Introduction: Abiraterone acetate, potent selective irreversible inhibitor of CYP17A1, is increasingly used with prednisone to treat prostate cancer resistant to androgen deprivation therapy.

Case Presentation: 64-year-old gentleman with BG of prostate cancer with widespread metastatic bone disease. He was on abiraterone since 2019. Admitted with generally unwell, aches/pains, headache, and dizziness. Euvolemic hyponatremia (123) with normal potassium and glucose. Blood pressure was 100/60mmHg. Morning cortisol 87 nmol/l, TSH 1.4 mu/l, serum osmolality 252 mmol/kg, urine osmolality 327 mosm/kg and urine sodium of 38 mmol/l. Short synacthen test - stimulated cortisol 296 nmol/l. On further enquiry, he was earlier taking prednisolone 5mg once daily with abiraterone. However, discontinued recently causing symptomatic adrenal insufficiency. The prednisolone restarted at 10mg with planned reduction to 5mg once feeling better. Unfortunately, he developed metastatic small cell carcinoma and had to start carboplatin/etoposide chemotherapy with discontinuation of Abiraterone and prednisolone. Later the year, he succumbed to disease.

Discussion: CYP17A1 has 2 roles: as 17-α hydroxylase and 17,20 lyase. 17-α hydroxylase catalyses conversion of pregnenolone to 17-hydroxypregnenolone and progesterone to 17-hydroxyprogesterone, which are precursors for cortisol. 17,20 lyase catalyses dehydroepiandrosterone and androstenedione production which are precursors of testosterone. Inhibition of 17-α hydroxylase and 17,20 lyase by abiraterone decreases cortisol and testosterone production. CYP17 inhibition by abiraterone: loss of negative feedback, high ACTH levels, and mineralocorticoid excess syndrome (MES) through uninhibited steroidogenesis pathway – hypokalemia, fluid retention, and hypertension. Addition of glucocorticoid to abiraterone attenuate development/severity of MES. Lowering excess ACTH also reduces ACTH-driven androgen formation via a backdoor pathway. Adrenal insufficiency in our case could be due to 17-α hydroxylase inhibition or to secondary adrenal insufficiency from long term steroid withdrawal. ACTH level should have helped in differentiation. In either case, patient needed prednisolone in double dose during this unwell period for symptomatic improvement.