Ectopic Cushing's syndrome is rare, accounting for 510% of all cases of Cushing's. The majority are casued by small cell lung cancer and neuroendocrine tumours.
We report a case of a 59 year old male who presented with osmotic symptoms after newly diagnosed diabetes, hypokalaemia and metabolic alkalosis with clinical features suggestive of Cushing's. Initial random cortisol was >2000 nmol/l and 24 hour urine cortisol 14500 nmol/l (99378 nmol). Both low and high dose dexamethasone suppression tests failed to supress, being 2069 nmol/l and 2550 nmol/l respectively. ACTH was 580 ng/l (<50 ng/l). His pituitary MRI was normal. Adrenal CT showed bilateral adrenal hyperplasia suggestive of ectopic ACTH production with also evidence of liver metastases. A staging CT revealed a left hilar mass (T2bN3M1b). A liver biopsy confirmed poorly differentiated neuroendocrine tumour. Initial management included insulin and metyrapone. The cortisol levels decreased to 600800 nmol/l. Diabetes control remained poor. Palliative chemotherapy with Carboplatin and Etoposide resulted in a marginal decrease in the size of the lung mass and liver metastases. Poorly controlled diabetes, recurrent infections, progressive oedema and proximal myopathy increased comorbidity. Follow-up scan 2 months later showed increasing size of the lung primary with additional metastases in the adrenals and bones with multiple pulmonary emboli. Second line chemotherapy provided some symptom relief however he deteriorated rapidly and died.
Ectopic ACTH production is associated with poor response to chemotherapy, short survival and a high rate of complications to therapy. Studies have shown variations in clinical course can be ascribed to aggresive transformation resulting in liver and adrenal metastases.