Endocrine Abstracts

Background

Ectopic ACTH secretion accounts for 9–18% of ACTH dependent Cushing’s’ syndrome. The most common causes are intrathoracic neuroendocrine tumours. Gastric tumours as a cause of ectopic ACTH secretion are remarkably rare.

Case report

A seventy-five-year-old gentleman complained of a four month’s history of epigastric discomfort, anorexia, and weight loss. He was a known diabetic and hypertensive. A computed tomography (CT) scan showed diffuse enhancement and thickening of the pylorus up to the pyloric antrum for a length of eight centimetres with large hepatic and coeliac lymph node metastases. An oesopho-gastro-duodenoscopy showed an ulcerating mitotic lesion on posterior antral wall, extending from the antrum through the pylorus and into the first part of the duodenum. Within two weeks he developed recurrent vomiting, new onset lower limb oedema and orthopnoea. His diabetes and hypertension had suddenly become difficult to control. Blood results showed severe new onset hypokalaemia of 1.75 mmol/l with metabolic alkalosis. ECG showed global T wave inversions and U waves. The combination of hypokalemia, metabolic alkalosis and a stomach lesion triggered a series of investigations to assess if severe hypercortisolaemia could be the underlying diagnosis. A 9am cortisol level was 3325 (145–619 nmol/l), overnight dexamethasone suppression test 2602 (< 50 nmol/l), 24 hr urinary cortisol 4316 (57.7–806 nmol/24 hrs) and ACTH levels 358 (10 48 pg/ml). Gastric biopsies showed a moderately to poorly differentiated intestinal-type adenocarcinoma with neuroendocrine differentiation. The poorly differentiated component expressed neuroendocrine markers CD56, synaptophysin and chromogranin, the latter being weakly expressed. Ki 67 index was 70%. It was concluded that the patient had a non-neuroendocrine neoplasm with a focal neuroendocrine component secreting ACTH. The hypokalaemia was managed with aggressive central and peripheral potassium replacement and spironolactone. Metyrapone was started to block adrenal cortisol synthesis with doses being cautiously titrated according to his 24 hour urinary cortisol results. These decreased to 1254 and 1822 nmol/24hrs. Insulin was started. He was unfit for surgery and was planned for six cycles of a combination of Carboplatin/Etoposide chemotherapy once every 3 weeks. He received three cycles of Carboplatin but his health deteriorated. Repeat CT scan showed an increase in liver metastases and adrenal hypertrophy. He was given adequate pain relief, fluids and he died a few days later.

Conclusion

This case highlights the accelerated presentation, rapid malignant progression and poor prognosis of hypercortisolism due to ectopic ACTH secretion.