Zollinger-Ellison syndrome; Z-E syndrome; ZES
Gastrinomas are neuroendocrine tumours that produce large quantities of the hormone gastrin, which stimulates the production of excess gastric acid from the stomach. Most of these tumours are found either in the duodenum (first part of the small intestine) or the pancreas. Very rarely they have been found in liver, stomach, bile duct, heart and lung.
Gastrinomas arise due to uncontrolled division and replication of cells in the gut called G cells, which produce the hormone gastrin. Under normal conditions gastrin can increase stomach acid and help with the digestion of food. Gastrinomas can produce large amounts of gastrin resulting in increased acid production which can cause ulcers in the stomach and small intestine. Gastrinomas often develop spontaneously (sporadic tumours) However, in approximately 20-30% of patients these tumours may develop as part of a syndrome called multiple endocrine neoplasia type 1 (MEN1). In MEN1 they are associated with a defect in a gene called MENIN. The trigger for sporadic gastrinomas is not known but they are commonly associated with spread to the liver (60–90% of patients) and adjacent organs at the time of diagnosis.
The signs and symptoms of gastrinomas are related to increased gastric acid production, this is caused by the excess gastrin hormone that is produced by the tumour cells. Most patients experience abdominal pain, heartburn, nausea, diarrhoea, blood in the vomit and/or bleeding from the back passage. On average symptoms may be present up to five years before a definitive diagnosis of gastrinoma being established.
Ulcers of the stomach and small intestine are not uncommon in the general population, however only a very small number of these ulcers occur due to the presence of a gastrinoma, (approximately 0.1% ( 1 in 1000) of patients who have ulcers in these locations). The diagnosis of gastrinoma may be suspected in patients with stomach or small intestinal ulcers if they:
Gastrinomas are rare; they have an incidence of 0.5–3 new cases per million of the population per year. They are slightly more common in men compared with women (1.5 : 1).
Most sporadic gastrinomas are diagnosed in people aged between 50 to 60 years. Gastrinoma tumours arising as part of the genetic condition multiple endocrine neoplasia type 1 are usually diagnosed at a younger age (20’s to 30’s).
Most gastrinomas occur sporadically; however, in about 20-30% of patients these tumours are inherited as part of multiple endocrine neoplasia type 1 syndrome(MEN1). As mentioned MEN1 occurs due to a defect in the MENIN gene. As the name suggests MEN1 is characterised by tumours arising in different hormone producing organs of the body, most frequently affected are the pancreas, parathyroid and pituitary glands. The defects in the MENIN gene can be passed from an affected individual to their offspring.
Gastrin measurement
The diagnosis of a gastrinoma is based on confirming that there is a high level of gastrin in the blood when the person is fasting. However, proton pump inhibitors (PPI) such as omeprazole or lansoprazole, a treatment for indigestion can interfere with the results. This can cause diagnostic difficulties and PPI medication is often stopped temporarily before the gastrin blood test is taken, when it is safe to do so.
Secretin test
In cases where the measurement of gastrin while fasting is inconclusive a secretin test may be carried out. Secretin is a hormone produced by the small intestine, which stimulates pancreatic and small intestinal secretions, in this case it will cause a gastrinoma to release more gastrin. The test requires an injection of secretin into the blood, if this causes a rise in gastrin levels, along with evidence of increased acid production in the stomach – measured during an endoscopy, this would suggest an underlying diagnosis of gastrinoma. This test is usually carried out in an outpatient setting.
Imaging studies
To locate the gastrinoma, certain scans such as a computerised tomography (CT) or magnetic resonance imaging (MRI), may be performed. In addition to identifying the location of the gastrinoma the scans, may also determine if there has been any spread of the tumour cells to other organs. However, often gastrinoma are small and may not be seen on CT or MRI. In such cases a procedure called an endoscopic ultrasound may be carried out; this is where a camera is passed down through the oesophagus, stomach and through the first part of the small intestine, it is very useful for assessing the pancreas for the presence of small tumours. During the procedure it is possible to take a biopsy – a small sample of the tumour, to be looked at under the microscope to confirm diagnosis. Specialised scans are also used to identify gastrinomas that have not been identified using other imaging studies and they may also be used to identify whether the tumour has spread to other organs. These include somatostatin receptor scintigraphy (SRS/OctreoScan) and 68gallium-labelled somatostatin tracer PET/CT(positron emission tomography/computerised tomography) scan.
Treatment decisions will be based on the size, location, spread of the tumour and whether is has developed as part of a MEN1 syndrome or not.
Surgical treatment:
In cases where the gastrinoma is localised to the pancreas or small intestine without any evidence of spread to other organs, surgical removal of the tumour can cure the disease. The extent of the surgery will depend on the exact location and size of the the tumour. In the majority of patients however, the tumour will have spread to other organs at the time of diagnosis. While in many situations this means that a surgical cure cannot be achieved, in some case where the spread of the tumour remains limited, surgery may be considered if it is believed a cure can be achieved.
Medical treatment:
Medical treatment of gastrinoma includes use of high doses of acid-blocking agents such as proton pump inhibitors or H2 receptor antagonists. These medications can be used on a long-term basis to reduce gastric acid secretion, which relieves the symptoms and promotes the healing of ulcers in the small intestine and stomach.
In patients where the gastrinoma has spread to the liver (metastasised) and surgical treatment will not achieve a cure, somatostatin analogues such as octreotide/lanreotide may be used for stabilisation of the disease. In some cases where the tumour spread is aggressive alternative treatments are may be used and these include:
In cases where the tumour has not spread to any adjacent organs and may successfully be removed by surgery, patients should go on to lead full and active lives. They will be followed up as sometimes there can be long-term issues with pancreatic hormones and enzymes not being produced in usual amounts, this can affect food absorbtion and occasionally development of diabetes. Patients treated with surgery will need to attend regular hospital checks to assess for recurrence of the tumour using blood tests or radiological investigations.
Gastrinoma, if left untreated, can lead to ulcers, perforation and bleeding from the stomach and small intestine. These neuroendocrine tumours are usually slow growing and proton pump inhibitors are highly effective in controlling the symptoms. However, when they spread to other organs such as the liver and a cure cannot be achieved then this can limit life expectancy.
Last reviewed: Jan 2019
