8 - Non-B Islet Tumours and the Syndrome of Watery Diarrhoea, Hypokalaemia and Hypochlorhydria

Abstract

The diarrhoeogenic syndrome (WDHA, WDHH, pancreatic cholera, Verner–Morrison syndrome) is reviewed and the 64 reported cases are summarised. Clinical manifestations present in all patients include watery diarrhoea, hypokalaemia with potassium levels less than 3.5 m.Eq/1, absence of peptic ulcer disease except during adrenal corticosteroid administration or following surgery, hypochlorhydria or achlorhydria, and pathological findings of non-B pancreatic islet hyperplasia, adenoma or carcinoma. Associated findings in over 50 per cent of patients include hypercalcaemia, glucose intolerance, and temporary adrenal corticosteroid responsiveness of the diarrhoea. The hypercalcaemia is usually cured only by resection of the pancreatic disease, suggesting that the tumour secretions are causative of hypercalcaemia. Less common manifestations include flushing, skin eruptions, tetany in the presence of normal or high serum calcium levels, dilated gallbladder, psychosis, renal failure, and congestive heart failure. The latter two manifestations are in all likelihood secondary to hypokalaemia. The diarrhoeogenic substance produced by the tumour cells is being investigated vigorously in many laboratories. Current studies show some evidence that the tumours secrete a gastric inhibitory substance similar to secretin, enterogastrone or gastrone or an independent gastric inhibitory polypeptide. It is likely that the substances, when completely defined, will cause increased biliary and pancreatic or small intestinal secretions and possibly will also block reabsorption of such fluid and electrolytes in the small intestine. The proper treatment for the diarrhoeogenic syndrome is surgical excision of any gross tumour or subtotal distal pancreatectomy where no gross abnormalities are present at surgery. Total pancreatectomy is occasionally necessary in patients with diffuse non-B islet hyperplasia. The prognosis is good and approximately 50 per cent of the patients have clinical remission following surgery, particularly where malignant transformation has not occurred. It is stressed that early diagnosis and treatment is essential. It is postulated that the pancreatic non-B islet tissue may be responding to some trophic hormone or substance secreted by some organ remote from the pancreas.