Pathophysiology:
The tumour secretes gastrin, which stimulates acid secretion to its maximal capacity and increases the parietal cell mass three- to sixfold. The acid output may be so great it reaches the upper small intestine, reducing the luminal pH to 2 or less. Pancreatic lipase is inactivated and bile acids are precipitated. Diarrhoea and steatorrhoea result. Around 90% of tumours occur in the pancreatic head or proximal duodenal wall. At least half are multiple and tumour size can vary from 1 mm to 20 cm. Approximately one-half to two-thirds are malignant but are often slow-growing. Between 20% and 60% of patients have multiple endocrine neoplasia (MEN) type 1.
Clinical features
The presentation is with severe and often multiple peptic ulcers in unusual sites, such as the post-bulbar duodenum, jejunum or oesophagus. There is a poor response to standard ulcer therapy. The history is usually short, and bleeding and perforations are common. Diarhoea is seen in one-third or more of patients and can be the presenting feature.
Investigations
Hypersecretion of acid under basal conditions, with little increase following pentagastrin, may be confirmed by gastric aspiration. Serum gastrin levels are grossly elevated(10- to 1000-fold). Injection of the hormone secretion normally causes no change or a slight decrease in circulating gastrin concentrations, but in Zollinger-Ellison syndrome it produces a paradoxical and dramatic increase in gastrin. Tumour localisation (and staging) is best achieved by a combination of CT and EUS; radio-labelled somatostatin receptor scintigraphy and gallium DOTATATE PET scanning may also be used for tumour detection and staging.
Management
Some 30% of small and single tumours can be localised and resected but many tumours are multifocal (especially in the context of MEN 1). Some patients present with metastatic disease and, in these circumstances, surgery is inappropriate. In the majority of these individuals, continuous therapy with omeprazole or other PPIs can be successful in healing ulcers and alleviating diarhoea, although double the normal dose is required. The synthetic somatostatin analogue, octreotide, given by subcutaneous injection, reduces gastrin secretion and may be of value. Overall 5-year survival is 60-75% and all patients should undergo genetic screening for MEN 1.
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