Zollinger-Ellison syndrome; Z-E syndrome; ZES
Gastrinomas are neuroendocrine tumours that produce large quantities of the hormone gastrin, which stimulates the production of gastric acid in stomach. Most of these neuroendocrine tumours are found either in the duodenum (first part of the small intestine) or the pancreas. Rarely they have been found in the stomach, bile duct, liver, ovaries and heart. Gastrinomas may be sporadic or in about 25% of patients as part of multiple endocrine neoplasia type 1 (MEN1). Sporadic gastrinomas are commonly associated with spread to the liver (60–90% of patients) and adjacent organs at the time of diagnosis.
Gastrinomas arise due to uncontrolled division and replication of specialised G cells, which produce the hormone gastrin. In MEN1 they are associated with a germline mutation in the MENIN gene. The trigger in sporadic gastrinomas is not known.
The signs and symptoms of gastrinomas are related to increased gastric acid production by the neuroendocrine tumour cells. Most patients experience abdominal pain, heartburn, nausea, blood in the vomit, bleeding from the back passage and diarrhoea. On average these symptoms are present for five years prior to a definitive diagnosis of gastrinoma being established.
Gastrinomas may be present in 0.1% of patients who have ulcers in their stomach or small intestine. The diagnosis of gastrinoma should 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 randomly occurring gastrinomas are diagnosed in the 50s to 60s. Neuroendocrine tumours arising as part of the genetic condition multiple endocrine neoplasia type 1 are usually diagnosed at a younger age (20s to 30s).
Gastrinomas are the most common of the functional pancreatic neuroendocrine tumours accounting for 30% of cases.
Most gastrinomas occur sporadically; however, in about 20% of patients these tumours are inherited as part of multiple endocrine neoplasia type 1 syndrome.
The diagnosis of a gastrinoma is based on high fasting gastrin levels in the blood. However, proton pump inhibitors (PPI) such as omeprazole or lansoprazole – a treatment for indigestion – can cause false positive results. If there is history of gastric ulceration/bleeding then PPI should not be stopped as deaths have been reported in patients with gastrinoma where a PPI has been withdrawn. This can cause diagnostic difficulties.
In this case a secretin test may be done. Secretin is a hormone produced by the small intestine, which stimulates pancreatic and small intestinal secretions. If injection of secretin into the blood causes a rise in levels of gastrin, 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.
To locate the gastinoma some scans, such as a computerised tomography (CT) or magnetic resonance imaging (MRI), may be performed. These will also show if there has been any spread to other organs such as the liver. However, often gastrinoma are small and may not be seen on CT or MRI. 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, and can visualise the pancreas in great detail. This helps in the diagnosis to visualise smaller tumours, particularly in the pancreas. 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.
Somatostatin receptor scintigraphy (SRS/OctreoScan) is a useful scan in which low levels of radiation are used for diagnosis of gastrinoma along with assessing any spread of the tumour to other organs. A gallium 68 PET scan may also be helpful in checking where disease has spread outside the pancreas.
In cases where the gastrinoma is localised to the pancreas or small intestine without any evidence of spread to the liver or bone, surgical removal of the tumour can cure the disease. Surgical treatment includes removal of part of the pancreas, or a larger operation called a Whipples procedure, which involves removal of part of the pancreas, stomach and duodenum. However, in the majority of patients the tumour has spread to other organs at the time of diagnosis so surgical removal is not possible.
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), somatostatin analogues such as octreotide/lanreotide may be used for stabilisation of the disease as monthly injections. Chemotherapy, tyrosine kinase inhibitors, peptide targeted radionuclide therapy (PRRT) or hepatic arterial embolisation may be used to treat more aggressive disease that is progressing or causing significant symptoms.
There are general risks associated with surgery such as possible loss of blood, infection and pain following surgery. Long-term use of proton pump blockers has been linked with development of vitamin B12 deficiency. Somatostatin analogue therapy is associated with side-effects such as nausea, diarrhoea, worsening of diabetes control and gallstone formation. Chemotherapy is associated with side-effects such as bone marrow suppression, loss of hair (alopecia) and gastrointestinal disturbance. Patients should discuss any concerns about these possible side-effects with their doctor or specialist.
In cases where the tumour has not spread to any adjacent organs and has been successfully 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 dysfunction with hormones and enzymes not being produced in usual amounts, causing food to not be absorbed, 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 small intestine. These neuroendocrine tumours are usually slow growing and proton pump inhibitors are highly effective in controlling the symptoms. However, when they metastasise and spread to other organs – such as the liver, they then are described as a malignant cancer and will not be curable and so will limit life expectancy.
Last reviewed: Feb 2017