Severe cushings syndrome associated with metastatic prostate adenocarcinoma
Akrem Elmalti1, AN Arefin1, M Thomas1, R Jenkins2 & S Orme2
Introduction: Prostate carcinoma is a recognised yet rare cause of Cushings syndrome. This report describes two cases in which Cushings syndrome was associated with advanced prostate cancer.
Case 1: A 70-year man presented with a very short history of swelling of his face and legs. He was known to have prostate adenocarcinoma with bony metastases. He was hypokalaemic and resistant to standard potassium replacement. He had a Cushingoid appearance, hypertension, hypokalaemic alkalosis and hyperglycaemia. His 0900 cortisol and ACTH were 1432 nmol/l (NR 150600) & 297 ng/l (NR <47) respectively. Cortisol levels at midnight and after an overnight 1 mg dexamethasone suppression test (DST) were 3138 and 2692 nmol/l respectively. 0900 cortisol levels at baseline and after a two-day low dose DST were 3886 and 3831 nmol/l respectively. Two 24-hour urinary free cortisol levels were 24,376 and >100,000 nmol/day. A pituitary MRI scan and baseline pituitary hormones were normal. A CT scan showed prostatic carcinoma with bone metastases. He was treated with metyrapone 250 mg qds, spironolactone and potassium replacement. Unfortunately he deteriorated rapidly and died from pneumonia.
Case 2: A 63 year old man with metastatic prostate carcinoma presented with a short history of weight loss and peripheral oedema. Tests revealed hyperglycaemia and hypokalaemic alkalosis. Random serum cortisol and ACTH were 1735 nmol/l and 244 ng/l respectively; 24-hour urinary free cortisol was 23,000 nmol/day. CT scan showed widespread metastases. Despite treatment with metyrapone, ketoconazole and a continuous etomidate infusion there was no biochemical or clinical response and he died of sepsis.
Conclusion: Cushings syndrome can occur in association with advance prostate carcinoma and can run an extremely aggressive course. Both reported patients died of sepsis likely related to the extremely high cortisol levels. Clinicians need to rapidly recognise and aggressively treat infection in such patients.