Overview

What is Zollinger-Ellison syndrome?

Zollinger-Ellison syndrome (ZES) is a very rare condition that affects your digestive system. It results from a type of tumor called a gastrinoma which may develop in your pancreas and/or duodenum (the top of your small intestine). Gastrinomas produce large amounts of the hormone gastrin, which is what triggers your stomach to produce gastric acid. Too much gastrin leads to too much stomach acid, which can cause ulcers in your stomach and duodenum. ZES is also known as pancreatic ulcerogenic tumor syndrome.

How does Zollinger-Ellison syndrome affect me?

Most people with Zollinger-Ellison syndrome have complications related to too much stomach acid. Common side effects include diarrhea and acid reflux. Most people (90%) will develop ulcers in their stomach and intestines. Severe peptic ulcer disease can be serious. It can cause gastrointestinal bleeding and scarring in your gastrointestinal (GI) tract. Scar tissue can cause an obstruction. In addition, about half of gastrinomas may become cancerous (malignant). Malignant tumors are likely to metastasize or spread.

Who gets Zollinger-Ellison syndrome?

Gastrinomas are estimated to affect between 1 to 2 people per million every year. Most physicians have never seen a case. You’re more likely to get them if you have a family history of multiple endocrine neoplasia (MEN) type 1. About 25% of people with Zollinger-Ellison syndrome have this rare genetic disorder, which causes tumors in various glands throughout your endocrine system. However, most people who get gastrinomas get them for unknown reasons. They’re usually diagnosed in middle age.

Symptoms and Causes

What causes Zollinger-Ellison syndrome?

Tumors are masses of cells that continue to grow by overproducing. Sometimes a gene mutation changes the coding in your DNA that controls how much certain cells replicate. In other cases, we don’t know why certain cells overproduce, or why they do so more aggressively in some people than others. We do know that too much of any type of cell can be bad for your body. When you have too many neuroendocrine cells producing gastrin, the result is too much gastric acid in your body.

What are the symptoms of high gastrin levels in Zollinger-Ellison syndrome?

Not everyone with Zollinger-Ellison syndrome notices the effects of high gastrin levels. Some people with smaller and fewer tumors may have less gastrin and less stomach acid than others. Some people who have ulcers can’t feel them. These are called “silent ulcers.” A small percentage of people experience diarrhea as their first symptom. However, most people experience the classic symptoms of peptic ulcer disease. These can be mild to severe. Common symptoms before complications include:

Burning or gnawing stomach pain.
Acid reflux and heartburn.
Indigestion, especially of fatty foods.
Greasy, fatty poops or chronic diarrhea.

If you have complications of peptic ulcer disease, you may have other symptoms, such as:

Symptoms of gastrointestinal bleeding, like blood in your vomit or in your poop.
Symptoms of anemia from blood loss, like pale skin, weakness and fatigue.
Esophagitis from acid reflux irritating your esophagus.
Loss of appetite, nausea, vomiting and weight loss.

Diagnosis and Tests

How do you diagnose Zollinger-Ellison syndrome?

Your healthcare provider will begin by asking about your medical history and symptoms. If your history and symptoms suggest Zollinger-Ellison syndrome, they will order lab tests to check your gastrin levels and/or your stomach acid levels. If these results are high, they may use one or several imaging tests to look for gastrinomas in your digestive system. They’ll want to know how many you have, where they are and how big they are. In some cases, they may want to sample one to check it for cancer.

What tests are involved in the diagnosis of Zollinger-Ellison syndrome?

Tests may include:

Blood test. A blood test can show high levels of gastrin in your circulation. High gastrin can be caused by other things besides gastrinomas, but it’s a place to start. For the test, your healthcare provider will draw a small sample of blood from one of your veins and test it in a lab.
Stomach acid test. Your healthcare provider may want to directly test your stomach acid levels. They do this by drawing a fluid sample from your stomach through a nasogastric tube (you’ll have medication to make this easier). This is sometimes called a gastric acid secretion test.
Radiology. Your healthcare provider may try to spot gastrinomas with various imaging tests, such as an ultrasound, a CT scan or an MRI. These methods are relatively noninvasive because they don’t go inside your body. However, gastrinomas don’t always show up on these tests.
Endoscopy. Endoscopic procedures can give your healthcare provider a closer look inside your body. These procedures involve passing an endoscope (a lighted camera on a long tube) down your throat and into your stomach and duodenum. An upper endoscopy lets your provider see your upper gastrointestinal tract and nearby organs, including your pancreas. An endoscopic ultrasound combines endoscopy and ultrasound together for more detailed images. Your provider may use endoscopic ultrasound to guide a needle to your tumor and take a sample.

Management and Treatment

What are the treatment options for Zollinger-Ellison syndrome?

Medication

In most cases, healthcare providers can successfully treat your excess stomach acid with medication. Proton pump inhibitors (PPIs) are the most typical medication prescribed, and they work well for most people. These medicines stop the chemical chain reaction called the “proton pump” that occurs in your stomach lining to produce stomach acid. Reducing acid allows ulcers and eroded tissues in your stomach, duodenum and esophagus to heal. It also relieves symptoms such as stomach pain and diarrhea.

PPIs include:

Most people don’t have side effects, but side effects can include:

Headaches.
Indigestion.
Diarrhea.
Constipation.
Nausea.
Itching.

Surgery

When it’s possible, healthcare providers often prefer to find and remove gastrinomas in surgery to prevent them from growing and spreading. However, this can be technically difficult. Not all people are candidates, and not all medical centers are experienced in finding and removing gastrinomas. It’s easier if you have fewer lesions. When the tumors multiply and spread, they usually go to your lymph nodes and liver first. This could mean removing lymph nodes or part of your liver in addition to tumors.

Cancer therapies

Additional treatments for cancerous gastrinomas may include:

Chemotherapy.
Radiation therapy.
Gastrectomy (stomach removal).
Liver transplant (for metastatic cancer).

These treatments aren’t curative, but they can reduce and slow the spread of cancer, relieve symptoms and extend your life.

Is there a cure for Zollinger-Ellison syndrome?

Some cases can be cured by surgery if all of the gastrinoma cells are completely removed. However, studies suggest that only a minority of cases are curable this way. It may not be possible to remove all of the tumor cells if you have metastatic cancer that has spread beyond the original location, or if you have a condition like multiple endocrine neoplasia that causes multiple tumors in multiple places. Even when the tumors are successfully removed, you may continue to need to take medication for stomach acid.

Outlook / Prognosis

What is the prognosis for Zollinger-Ellison syndrome?

The prognosis depends on whether your tumors are malignant or not and how effectively they can be treated. Gastrinomas that aren’t cancerous tend to grow slowly, and if you’re treating your stomach acid effectively, they may not bother you much. If you do have cancer, your prognosis depends on whether it can be removed in surgery. The 10-year survival rate is 90% among those who are successfully treated with surgery. When surgery isn’t possible or isn’t curative, the 10-year survival rate is 25%.

A note from Cleveland Clinic

Zollinger-Ellison syndrome is rare and occurs for mostly unknown reasons. It’s always a surprise to be diagnosed with a rare condition, especially if you haven’t had a lot of symptoms. You’ll want to know what this means for you, and the answer to that can vary widely. For some people, it’s relatively easy to treat. For others, it can be severe or even fatal. Earlier diagnosis can allow your healthcare provider to intervene before serious complications develop and before cancer appears or spreads.

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Zollinger-Ellison Syndrome