Ectopic ACTH syndrome (EAS) is characteristically associated with neuroendocrine tumours and small cell carcinomas (SCC) typically of the bronchus. We report a rare case of EAS secondary to gastric adenocarcinoma.
A 52-year old man presented to our department with a few week history of proximal myopathy, easy bruising, anxiety and weight loss. He was tanned and hypertensive. Laboratory investigations revealed hypokalaemia (2.3 mmol/l), hyperglycaemia and anaemia. Serum ACTH was 210 ng/l (046) and serum cortisol 3360 nmol/l at midnight and failed to suppress following low (basal cortisol 4160 nmol/l, day 2 cortisol 3930 nmol/l) and high dose dexamethasone (day 2 cortisol >2069 nmol/l). Chest and abdominal computed tomography revealed extensive liver metastases, bilateral adrenal hyperplasia and thickening of the greater stomach curve. An oeasophago-gastroscopy (OGD) found a large gastric ulcer, biopsy of which revealed poorly differentiated adenocarcinoma. Immuno-histochemistry was negative for ACTH. A pituitary MRI found no adenoma. He was treated with metyrapone and underwent chemotherapy (epirubicin, cisplatin, carboplatin) but died 6 weeks following admission.
The association of EAS with gastric adenocarcinoma has only been described previously in 2 patients. However, as 614% of these tumours immuno-stain for ACTH, its prevalence maybe under-reported.
One feature of highly malignant tumours causing EAS is failure to stain for pro-opiomelanocortin derived peptides. This may be due to high peptide hormone secretion as indicated by excessively high circulating ACTH leading to marked hypercortisolaemia. The moderate ACTH levels in this patient may be due to secretion of precursor ACTH forms, not immuno-reactive to our antiserum or co-secretion of ACTH with a peptide(s) directly stimulating cortisol release from the adrenals such as gastric inhibitory peptide.
EAS has also been reported in association with gastric and oesophageal carcinoids and oesophageal SCC. An OGD should be considered to localise ACTH-producing tumours, in cases where the origin is unclear.