Zollinger-Ellison syndrome is a rare disorder that usually occurs when a tumor called a gastrinoma develops in the pancreas or duodenum.
A gastrinoma secretes a hormone known as gastrin, which results in an overproduction of acid in the stomach.
Gastrinomas that result in Zollinger-Ellison syndrome may originate from the pancreas or, less likely, from the small intestine. They occasionally stem from other organs in the body, for example, the lymph nodes, stomach, liver, and ovaries.
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Zollinger-Ellison syndrome is rare. Approximately, one in every million people will develop the syndrome, but it is most common among men aged 30 to 50 years.
Someone who has Zolllinger-Ellison syndrome will likely develop severe, recurrent ulcers of the esophagus, stomach, and the duodenum and jejunum, which are the upper portions of the small intestine. The ulcers form because of the excess acid.
Most people with Zollinger-Ellison syndrome have multiple tumors in the endocrine system, as well as tumors in the pancreas.
The signs and symptoms are similar to those of a peptic ulcer and include:
- discomfort in the upper abdomen
- burning and aching sensation in the upper abdomen
- bleeding in the digestive tract
- general weakness
- black, “tarry” feces, resulting from bleeding in the digestive tract
- unintentional weight loss
- low appetite or feeling full too quickly
It is not clear exactly what causes Zollinger-Ellison syndrome or the gastrinomas that develop.
Gastrinomas release excessive quantities of gastrin, which results in too much gastric acid in the stomach and duodenum. In time, this additional acid causes peptic ulcers to form in the lining of the duodenum. The result may be multiple ulcers that may cause pain or upper gastrointestinal bleeding.
As well as causing excess acid production, the gastrinomas may be malignant, or cancerous. The cancer can spread to other parts of the body, most commonly to nearby lymph nodes or the liver.
Most people develop Zollinger-Ellison syndrome for no apparent reason. However, a genetic condition called multiple endocrine neoplasia type 1 (MEN1) is responsible for 25 to 30 percent of cases.
MEN1 also causes multiple endocrine cancers.
A person has a 50 percent chance of developing Zollinger-Ellison syndrome from a parent who has the syndrome.
An individual may be at risk for developing a gastrinoma if they have had several family members with endocrine cancers, or if they have a family member with MEN1.
A doctor will ask the person about their symptoms and medical history and may carry out some tests.
High levels of gastrin in the blood may indicate that a person has tumors in their pancreas or duodenum.
Before taking the blood test, the person should:
- be fasting
- avoid acid-reducing medications for a time that the doctor will specify
They may need to repeat the blood test at least three times, as gastrin levels may fluctuate.
Stomach acidity level
People with chronic stomach inflammation and those who have recently undergone stomach surgery may have high levels of gastrin in the blood, even if the stomach does not produce much acid.
It is essential for the doctor to identify why the person has high gastrin levels, to find the correct treatment. They may test the acidity of the stomach.
If stomach acidity levels are not high, then it is highly unlikely the person has Zollinger-Ellison syndrome.
If the stomach is producing too much acid, a doctor may recommend a secretin stimulation test. This involves measuring gastrin levels, injecting the hormone secretin, and measuring the gastrin levels again.
If gastrin levels rise, this indicates that Zollinger-Ellison is present.
Upper gastrointestinal endoscopy
An upper gastrointestinal endoscopy involves a doctor inserting an endoscope into the person’s mouth, down the esophagus and into the stomach and duodenum to look for ulcers.
An endoscope is a long, thin tube that has light and video camera at the end that allows a doctor to see what is going on within particular parts of the body.
Other names for the procedure are:
- upper endoscopy
- upper GI endoscopy
- esophagogastroduodenoscopy (EGD)
The doctor may also take a biopsy, or tissue sample, from the duodenum to test for gastrin-producing tumors.
The doctor will recommend fasting for a specific time before this procedure.
A healthcare professional may locate tumors using:
In endoscopic ultrasound, the doctor inserts an endoscope with an ultrasound device inside the body. This enables them to see inside of the stomach and the duodenum.
An internal ultrasound helps to pinpoint tumors and take tissue samples. Individuals must fast for some time before this procedure.
Angiography can help to find tumors in the pancreas. A doctor inserts a catheter, which is a flexible tube, into arteries near the pancreas.
A health professional then injects a contrast dye into the blood vessel through the catheter. The dye shows up on X-ray images, highlighting blood vessels. These tend to be denser inside tumors.
Treatment for Zollinger-Ellison syndrome focuses on the tumors and ulcers. Various types of treatment are available.
Doctors will usually treat the tumors first.
Preventing tumor growth
Treatment options to stop tumor growth may include:
- chemotherapy, to slow the rate of growth of tumors
- removing gastrinomas from the liver can prevent other tumors from developing in the liver
- embolization, or cutting off the blood supply to the tumor
- injecting drugs directly into the tumor
Reducing gastrin production
The doctor may also use a hormone drug called octreotide to control symptoms. Octreotide is a medication that can reduce gastrin production.
Reducing acid levels
The first line of treatment for excess acid treatment is a proton pump inhibitor (PPI). This is a type of drug that helps to control excess acid production. PPIs reduce acid by blocking the action of tiny pumps inside acid-secreting cells.
Examples of PPIs include:
- esomeprazole (Nexium)
- omeprazole (Prilosec)
- lansoprazole (Prevacid)
- pantoprazole (Protonix)
- rabeprazole (Aciphex)
People with chronic Zollinger-Ellison syndrome can use pantoprazole delayed-release tablets as a long-term treatment option.
If stomach acid levels drop, peptic ulcers have a better chance to heal, and there will be fewer symptoms of Zollinger-Ellison syndrome.
Tumors can be difficult to remove because they tend to be small and hard to find. A surgeon might remove a single tumor but may not be able to perform surgery if there are several tumors, or if they have spread throughout the liver.
According to the National Organization for Rare Disorders (NORD), successful removal of a gastrinoma occurs in about 20–30 percent of cases.
If a person has a peptic ulcer, the doctor may suggest surgery to:
- close any damage or perforation that has occurred, for example, in the wall of the stomach or duodenum
- to remove a blockage caused by an ulcer
- to stop bleeding
In rare and severe cases, a surgeon may remove the stomach.
Most cases of Zollinger-Ellison syndrome are sporadic. This means that it does not stem from another condition, and it is not possible either to predict who will have it or ways to prevent it.
However, if there is a family history of MEN1 gene mutation, a doctor may recommend that a person undergoes predictive testing even if they do not have any symptoms.
At the age of 20 years, a person with the MEN1 gene mutation has a 50 percent chance of having symptoms. At the age of 40, the chance of developing symptoms rises to 95 percent, according to the Genetic and Rare Diseases Information Center (GARD).
If a person does not show symptoms by the age of 40 years, there is a good chance that they do not have a MEN1 mutation.
So far, there is no evidence that diet affects the risk of developing the syndrome.
The stomach, duodenum, and pancreas are part of the digestive system. The stomach and the pancreas secrete gastrin that stimulates the production of gastric acid and other digestive juices that help to break down food.
Gastrin travels in the bloodstream and signals to other stomach cells to release gastric acid to help break down food.
The food moves into the duodenum, the first part of the small intestine. There, secretions break it down further. The small intestine is the tube-shaped organ between the stomach and the large intestine.
In a healthy system, the stomach cells control how much gastrin a person produces. This prevents excessive quantities of gastric acid from forming.
In Zollinger-Ellison syndrome, there can be a disruption in the balance, because the gastrinomas produce extra gastrin.