Gastrinoma and Zollinger-Ellison syndrome: symptoms, diagnosis and treatment

Patient.info's professional reference describes Zollinger-Ellison syndrome (ZES) as an endocrine condition in which gastrin-secreting tumours cause multiple, refractory and recurrent peptic ulcers. Gastrin is the hormone that tells the stomach to make acid, so a tumour that produces it unchecked causes very high acid levels.

The tumour itself is a gastrinoma. It is usually in the duodenum or the pancreas, and in rare cases elsewhere in the abdomen or outside it. Cancer Research UK and Neuroendocrine Cancer UK describe neuroendocrine tumours as tumours of hormone-producing cells that can develop in places such as the stomach, bowel, pancreas or lung. Gastrinomas belong to this family.

Patient.info describes two main forms: sporadic, which occurs on its own, and a form associated with parathyroid and pituitary tumours as part of the inherited condition MEN1. About 20 to 30% of people with ZES have the MEN1 form. The mean age at presentation is around 40, younger in MEN1.

The NHS describes the main symptom of a stomach ulcer as tummy pain, usually in the upper tummy, which may feel like burning and is often worse at night, with indigestion, heartburn, bloating and feeling or being sick. In ZES these ulcer symptoms are present but can be more severe and more persistent.

Patient.info says upper abdominal pain suggestive of an ulcer is common, particularly in men and sporadic cases, and that diarrhoea is the other major feature, particularly in MEN1 and women, with many people having both. Reflux pain, nausea, vomiting and weight loss may also occur, and gastrointestinal bleeding is the presenting symptom in about 25% of patients.

The NHS says to see a GP if you have indigestion that does not go away with treatment or tummy pain that keeps coming back, and to ask for an urgent GP appointment or get help from NHS 111 if you have ulcer symptoms and the pain is getting worse or does not go away, or you have lost your appetite. It says to call 999 or go to A&E if you are vomiting bright red blood or your vomit looks like ground coffee, your poo has blood in it or is black, sticky and very smelly, or you have severe tummy pain.

Patient.info notes that ZES is easily treated at first as a simple peptic ulcer. Features that raise suspicion include persistent recurrence after treatment, ulcers further along the duodenum than usual, ulcers larger than 2 cm or multiple ulcers, ulcers alongside diarrhoea, and ulcers that are negative for Helicobacter pylori. It adds that nearly all duodenal ulcers are associated with H. pylori infection but that in ZES the very high acid alone can cause ulceration.

The NHS lists infection with Helicobacter pylori and regular use of anti-inflammatory painkillers such as ibuprofen as the main causes of stomach ulcers. A GP will usually test for these first, which is appropriate because they are far more common than ZES.

Patient.info says confirmation needs a raised fasting serum gastrin, followed by radiological or nuclear imaging to find the tumour. Fasting gastrin can also be raised by proton pump inhibitor treatment, other acid-suppressing medicines, kidney failure and chronic atrophic gastritis, so results are interpreted alongside stomach acid measurement. Where the gastrin level is not clearly high enough, a secretin stimulation test may be used, which Patient.info reports as having a sensitivity of 94% and specificity of 100%.

Once ZES is confirmed, Patient.info says to consider MEN1, checking calcium, parathyroid hormone and prolactin levels. Tumour localisation uses upper gastrointestinal endoscopy with careful inspection of the duodenum, followed by CT or MRI and somatostatin receptor scintigraphy, sometimes with endoscopic ultrasound. It says CT detects only about half of primary tumours and small ones of 1 cm or less are often missed. These tests are done in a specialist setting.

Patient.info says management is within specialist centres by multidisciplinary teams and includes medical suppression of gastric acid and surgical removal of the primary tumour to prevent malignant spread. Oral proton pump inhibitors are effective, but at a higher dose than usual, such as omeprazole 40 mg daily, and H2-receptor antagonists can also work with high, frequent dosing.

It says that because of the effectiveness of proton pump inhibitors, removal of the stomach is no longer routinely indicated. For sporadic gastrinomas, surgery with complete removal of the tumour and involved lymph nodes is the only curative treatment, and for sporadic ZES without metastases surgery decreases the risk of liver metastases. Surgery in MEN1 rarely achieves cure but may reduce the risk of spread and is recommended for tumours larger than 2.0 cm. Chemotherapy may be tried for metastatic disease. After surgery, gastrin levels are monitored, with imaging if they rise.

Complications of ulceration include bleeding and perforation, acid reflux can cause oesophagitis and stricture, and high acid can interfere with digestion. Patient.info says controlling acid secretion limits these complications.

Patient.info says the most significant factor in pancreatic gastrinoma is liver metastasis, with 15% 10-year survival with liver metastases compared with 95% 20-year survival without them. It lists other factors linked with poorer outcomes, including advanced stage, inadequate acid control and large pancreatic primary tumours. About 30 to 40% of gastrinomas are associated with liver metastases. Because outcomes depend so heavily on the individual tumour, your specialist team is the right source for what the figures mean for you.

If MEN1 is diagnosed, Patient.info says genetic counselling and testing of family members are recommended.

Because the condition is rare, diagnosis and treatment are usually coordinated through specialist neuroendocrine tumour services within the NHS, with a GP and gastroenterologist involved first. Some people also seek a private gastroenterology or endocrine opinion. Whichever route is used, ask whether care is coordinated by a specialist neuroendocrine multidisciplinary team, and who monitors gastrin and imaging over the long term.