Endocrine Abstracts

Introduction: Cushing’s syndrome (CS) secondary to ectopic adrenocorticotrophic hormone (ACTH)–producing prostate cancer is rare with less than 30 cases reported. We report a case of Cushing’s syndrome secondary to prostate adenocarcinoma with recurrent hypokalemia, sepsis and rapid disease progression. A 61-year-old man presented in January 2019 with 3-week history of lower limb swelling and weakness. Past medical history is significant for metastatic prostate cancer diagnosed in December 2018 for which he was started on gonadotropin-releasing hormone (GnRH) analogue. His other co-morbidities include hypertension and diabetes. On examination, he had ecchymoses of the upper limbs and proximal myopathy but no other features of Cushing’s syndrome. Blood investigations showed hypokalemia with metabolic alkalosis (potassium 2.5 mmol/l, bicarbonate 36 mmol/l) and 0800 h cortisol of 1229 nmol/l. Cushing’s syndrome was diagnosed after cortisol failed to suppress after a 1 mg overnight dexamethasone suppression test (cortisol 1327 nmol/l), and 48-hour 2 mg dexamethasone suppression test (cortisol 1447 nmol/l). This was likely to be ACTH-dependent as ACTH was 57.4 (normal range NR 10–60) ng/l and high dose 8mg dexamethasone did not suppress cortisol to less than 50% of baseline (cortisol 1424 nmol/l). His 24-hour urine free cortisol was 20475 (NR 59-413) nmol/day. MRI pituitary did not show any pituitary mass. 68Ga-DOTA-NOC PET-CT scan revealed an area of increased DOTA-NOC-avidity in the inferior aspect of the right side of the prostate gland. Review of his prostate biopsy done in December 2018 showed adenocarcinoma with no features of small cell carcinoma, but immunostaining positive for synaptophysin, CD 56 and ACTH. He was initiated on potassium replacement, ketoconazole and spironolactone with improvement of hypokalemia, blood pressure and glucose. Ketoconazole was switched to somatostatin analogue octreotide in view of progressive liver dysfunction. He eventually succumbed to by parainfluenza, varicella and bacterial bronchopneumonia with septic shock, 2 months after diagnsosis.

Conclusion: Adenocarcinoma of the prostate with neuroendocrine differentiation is a rare cause of ectopic Cushing syndrome. It is imperative to recognize and treat ectopic Cushing’s syndrome as it has an aggressive course with poor prognosis and limited treatment options.