Endocrine Abstracts

55 year old male was diagnosed with prostate acinar adenocarcinoma (wild type BRCA1/2 on somatic testing) in February 2023. PSA at diagnosis- 33.4ug/L and PSMA-PET confirmed widespread nodal and bone metastases. He was treated with combination of androgen deprivation therapy and Darolutamide and Docetaxel chemotherapy. His disease was subsequently controlled with PSA of 0.24ug/l. He presented in July 2024 with abdominal distention, pitting oedema, muscle weakness and exertional breathlessness. He had persistent hypokalaemia and metabolic alkalosis, new hyperglycaemia and hypertension (potassium- 2.1mmol/l, bicarbonate- 34.8 mmol/l, pH- 7.55, HbA1c- 62mmol/mol). CT confirmed progressive disease with multiple new hepatic metastases and there was rise in PSA to 4.3ug/l. His cortisol was 3321nmol/l following a 1 mg dexamethasone suppression test and ACTH- 951ng/L (0-46). Rise in PSA, biochemistry and imaging were in keeping with prostate cancer with neuroendocrine differentiation and ectopic cushing’s syndrome (ECS). Due to poor performance and need to commence chemotherapy immediately, histological diagnosis or neuroendocrine imaging were not pursued. Patient was unfit for bilateral adrenalectomy. Medical management with Metyrapone, Metformin and Spironolactone were commenced alongside Cabazitaxel chemotherapy. Abnormal liver function tests precluded addition of ketoconazole. Unfortunately, there was no clinical or biochemical response to two cycles of chemotherapy and Metyrapone dose escalation (ACTH- 2227 ng/l, Cortisol 1428 nmol/l) and patient sadly passed away within two months.

Discussion: Neuroendocrine differentiation can occur in 25-30% of metastatic-castrate resistant prostate cancer with prior use of androgen deprivation therapy and is associated with extremely poor prognosis. Ectopic cushing’s syndrome as a paraneoplastic phenomenon in this scenario is very rare and has been described in a small numberof reported cases. Persistent hypokalaemia, hypertension and new hyperglycaemia should alert clinicians to this possibility. Despite aggressive treatment of ECS often requiring a combination of rapid-acting steroidogenesis inhibitors, the overall prognosis remains very poor.