Alternative names for gastrinoma

Zollinger-Ellison syndrome; Z-E syndrome; ZES

What are gastrinomas?

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 (gastric triangle). Very rarely they have been found in liver, stomach, bile duct, heart and lung.

What causes gastrinomas?

• G cells in the stomach, pancreas and small intestine stimulate the parietal cells in the stomach.
• This produces the hormone gastrin. Usually, gastrin increases stomach acid to help with the digestion of food.
• Gastrinomas are overgrowth of G cells, which lead to production of excessive amounts of gastrin The increased acid production causes erosions or 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). 

What are the signs and symptoms of gastrinomas?

The signs and symptoms of gastrinomas are related to increased gastric acid production as shown in the figure below.

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). Some symptoms may increase suspicion of a Gastrinoma.

The diagnosis of gastrinoma may be suspected in patients with stomach or small intestinal ulcers if they:

• Are resistant to treatment
• Have recurrent ulcers
• Have associated complications such as intestinal perforation and bleeding
• Have other features of MEN1 syndrome e.g. elevated calcium levels
• Have a family history of MEN1 syndrome

What is Zollinger Ellison Syndrome?

Zollinger-Ellison syndrome is a rare syndrome caused by a gastrinoma, which is characterised by severe, recurrent, and multiple peptic ulcers in the first part of the small intestine (such as the duodenum) or pancreas. 

How common are gastrinomas?

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).

How are gastrinomas diagnosed?

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.

Specialised scans include somatostatin receptor scintigraphy (SRS/OctreoScan) and 68gallium-labelled somatostatin tracer PET/CT (positron emission tomography/computerised tomography) scan which are specific for secretion by neuroendocrine tumours like gastrinomas.

Tissue Biopsy:

Biopsy of suspicious areas can be done using endoscopic ultrasound; 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.

A biopsy is where a small sample of the tumour is taken to be looked at under a microscope to confirm diagnosis.

Are Gastrinomas cancerous?

Some gastrinomas are benign however majority are malignant which means that they may spread to nearby organs. Gastrinomas associated with MEN 1 are usually more aggressive than sporadic forms.

How is a Gastrinoma Treated?

Treatment decisions will be based on the size, location, spread of the tumour and whether it has developed as part of a MEN1 syndrome or not.

Treatment decisions are often made at multidisciplinary team (MDT) meetings (a meeting that takes place between different health care professionals to discuss a patient’s care) which may be a neuroendocrine MDT at a specialist centre and varies as below:

Management of symptoms:

High doses of acid-blocking agents such as proton pump inhibitors or H2 receptor antagonists may be needed 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.

Surgical Resection:

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.

Management of tumour progression:

In patients where the gastrinoma has spread to the liver (called metastasised) and surgical treatment will not achieve a cure and somatostatin analogues such as octreotide/lanreotide may be used for stabilisation of the disease.

In some cases where the tumour spread is aggressive then alternative treatments may be used and these include:

• Chemotherapy
• Tyrosine kinase inhibitors or mTor inhibitors
• Peptide targeted radionuclide therapy (PRRT)
• Trans-arterial embolisation/chemoembolization.

Are there any side-effects to the treatment?

• There are general risks associated with surgery such as possible loss of blood, infection and pain following surgery.
• Long-term use of proton pump inhibitors (PPI’s) has been linked with development of vitamin B12 deficiency and low magnesium levels; these can be monitored with blood tests. The use of PPI’s has also been linked to an increased risk of bone fractures.
• 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 although patients should discuss any concerns about these possible side-effects with their doctor or specialist as it will depend on the specific treatments used.
• PRRT can affect bone marrow and kidneys.
• Trans arterial embolisation can cause some discomfort and damage surrounding healthy liver tissue.

What are the longer-term implications of a gastrinoma?

• 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 absorption and occasionally the 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.