Zollinger-Ellison syndrome

Updated: 2022-11-04

Overview

Pancreas

Pancreas

The pancreas is a large organ that lies across your upper abdomen behind your stomach.

Zollinger-Ellison syndrome is a rare condition in which one or more tumors grow in the pancreas or in the upper part of the small intestine. The tumors are called gastrinomas. These gastrinomas produce large amounts of the hormone gastrin. Gastrin causes the stomach to produce too much acid, which leads to peptic ulcers. High gastrin levels also can cause diarrhea, belly pain and other symptoms.

Zollinger-Ellison syndrome may occur at any time in life. However, people usually find out they have it sometime between ages 20 and 60. Medicines to cut down stomach acid and heal the ulcers are the usual treatment. Some people also may need surgery to remove tumors.

Symptoms

Symptoms of Zollinger-Ellison syndrome may include:

• Stomach pain.
• Diarrhea.
• Burning, aching or discomfort in your upper abdomen.
• Acid reflux and heartburn.
• Burping.
• Nausea and vomiting.
• Bleeding in your digestive tract.
• Losing weight without trying.
• Loss of appetite.

When to see a doctor

See your health care provider if you have a burning, aching pain in your upper belly that won't go away — especially if you also have nausea, vomiting and diarrhea.

Tell your provider if you've been using nonprescription medicines to reduce stomach acid. These include omeprazole (Prilosec, Zegerid), cimetidine (Tagamet HB) or famotidine (Pepcid AC). These medicines may mask your symptoms, which could delay your diagnosis.

Causes

The exact cause of Zollinger-Ellison syndrome isn't known. But the pattern of events that occurs in Zollinger-Ellison syndrome typically follows the same sequence. The syndrome begins when one or more tumors form in your pancreas or a part of your small intestine called the duodenum. The duodenum is the section connected to your stomach. Sometimes the tumors form at other sites, such as the lymph nodes next to your pancreas.

Your pancreas sits behind and below your stomach. It makes enzymes that are needed for digesting food. The pancreas also makes many hormones, including insulin. Insulin is the hormone that helps control your blood sugar, also called glucose.

Digestive juices from the pancreas, liver and gallbladder mix in the duodenum. This is where most of your digestion happens.

The tumors that occur with Zollinger-Ellison syndrome are made up of cells that secrete large amounts of the hormone gastrin. For this reason, they are sometimes referred to as gastrinomas. Increased gastrin causes the stomach to make far too much acid. The excess acid then leads to peptic ulcers and sometimes to diarrhea.

Besides causing excess acid production, the tumors are often cancerous. Although the tumors tend to grow slowly, the cancer can spread elsewhere — most commonly to nearby lymph nodes or your liver.

Association with MEN 1

Zollinger-Ellison syndrome may be caused by an inherited condition called multiple endocrine neoplasia, type 1 (MEN 1). People with MEN 1 also have tumors in the parathyroid glands. They may have tumors in their pituitary glands as well.

About 25% of people who have gastrinomas have them as part of MEN 1. They also may have tumors in the pancreas and other organs.

Risk factors

If you have a first-degree relative, such as a sibling or parent, with MEN 1, it's more likely that you'll have Zollinger-Ellison syndrome.

Diagnosis

Your health care provider usually bases a diagnosis on the following:

• Medical history. Your provider asks about your symptoms and review your medical history.

• Blood tests. A sample of your blood is examined to see whether you have high gastrin levels. While high gastrin levels may suggest tumors in your pancreas or duodenum, high gastrin levels also can be caused by other conditions. For example, gastrin may be higher if your stomach isn't making acid or if you have had gastric surgery. Taking acid-reducing medicines also can raise gastrin levels.

  You need to fast before this test. You also may need to stop taking acid-reducing medicine. Because gastrin levels can vary, this test may be repeated a few times.

  You also may have a secretin stimulation test. Secretin is a hormone that regulates gastric acid. For this test, your provider first measures your gastrin levels. You'll then be given an injection of secretin. Your gastrin levels will be measured again. If you have Zollinger-Ellison, your gastrin levels will rise dramatically.

• Upper gastrointestinal endoscopy. This test requires sedation. An endoscopy involves putting a thin, flexible instrument down the throat and into the stomach and duodenum. This instrument is called an endoscope. It has a light and a camera at the end of it. It allows your provider to look for ulcers.

  During the endoscopy, tissue samples may be removed. This is called a biopsy. The tissue will be examined for gastrin-producing tumors.

  Endoscopy also can determine whether the stomach is making acid. If the stomach is making acid and the gastrin level is high, then the diagnosis of Zollinger-Ellison can be established. You will be asked to fast after midnight the night before the test.

• Endoscopic ultrasound. This procedure uses an endoscope fitted with an ultrasound probe. The probe makes it easier to spot tumors in your stomach, duodenum and pancreas.

  Your provider may remove a tissue sample through the endoscope. This test also requires fasting after midnight and sedation.

• Imaging tests. Your provider may use imaging techniques to look for tumors. One test is a nuclear scan called somatostatin receptor scintigraphy. This test uses radioactive tracers to help locate tumors. Other helpful imaging tests include ultrasound, computerized tomography (CT), magnetic resonance imaging (MRI) and Ga-DOTATATE PET-CT scanning.

Treatment

Treatment of Zollinger-Ellison syndrome focuses on treating the hormone-secreting tumors as well as the ulcers they cause.

Treatment of tumors

An operation to remove the gastrinomas requires a skilled surgeon because the tumors are often small and difficult to find. If you have just one tumor, your provider may be able to remove it surgically. But surgery may not be an option if you have many tumors or tumors that have spread to your liver. On the other hand, even if you have multiple tumors, your surgeon still may recommend removing a single large tumor.

In some cases, providers recommend other treatments to control tumor growth, including:

• Removing as much of a liver tumor as possible, a procedure known as debulking.
• Attempting to destroy the tumor by cutting off the blood supply, called embolization.
• Using heat to destroy cancer cells with a procedure called radiofrequency ablation.
• Injecting drugs into the tumor to relieve cancer symptoms.
• Using chemotherapy to try to slow tumor growth.
• Having a liver transplant.

Treatment of excess acid

Excess acid production can almost always be controlled. Medicines known as proton pump inhibitors are the first line of treatment. These are effective medicines for controlling acid production in Zollinger-Ellison syndrome.

Proton pump inhibitors are powerful acid-reducing medicines. They work by blocking the action of the tiny "pumps" within acid-secreting cells. Commonly prescribed medicines include lansoprazole (Prevacid), omeprazole (Prilosec, Zegerid), pantoprazole (Protonix), rabeprazole (Aciphex) and esomeprazole (Nexium).

Long-term use of prescription proton pump inhibitors has been associated with an increased risk of fractures of the hip, wrist and spine. People age 50 and older are at higher risk. However, this risk is small and should be weighed against their acid-blocking benefits.

Octreotide (Sandostatin), a medicine similar to the hormone somatostatin, may counteract the effects of gastrin and be helpful for some people.

Preparing for an appointment

Your symptoms may prompt you to visit your primary health care provider first. Your provider will likely refer you to a doctor who specializes in diseases of the digestive system, called a gastroenterologist. You also may be referred to an oncologist. An oncologist is a doctor who specializes in treating cancer.

Here's some information to help you get ready for your appointment and know what to expect.

What you can do

• Be aware of any pre-appointment restrictions. When you make the appointment, let your care team know if you take any medicines. Certain acid-reducing drugs, such as proton pump inhibitors or H-2 blockers, can affect the results of some tests used to diagnose Zollinger-Ellison syndrome. However, don't stop taking these medications without asking your provider.
• Write down any symptoms you're experiencing, including any that may seem unrelated.
• Write down key personal information, including any major stresses or recent life changes. Also write down what you know of your family's medical history.
• Make a list of all medications, vitamins or supplements you're taking.
• Write down questions to ask your provider.

Questions to ask your doctor

For Zollinger-Ellison syndrome, some basic questions to ask include:

• What's the most likely cause of my symptoms?
• Is there any other explanation for my symptoms?
• What tests do I need to confirm the diagnosis? How should I prepare for those tests?
• What treatments are available for Zollinger-Ellison syndrome, and which do you recommend for me?
• Are there dietary restrictions I need to follow?
• How often do I need to come back for follow-up appointments?
• What's my prognosis?
• Do I need to see a specialist?
• Is there a generic alternative for the medication you're prescribing for me?
• Are there websites you recommend to learn more about Zollinger-Ellison syndrome?
• Are any other medical problems more likely to occur because I have Zollinger-Ellison syndrome?

What to expect from your doctor

Your provider is likely to ask you a number of questions, including:

• When did you begin experiencing symptoms?
• Do you have symptoms all the time, or do they come and go?
• How severe are your symptoms?
• Does anything make your symptoms better?
• Have you noticed anything that makes your symptoms worse?
• Have you ever been told you have a stomach ulcer? How was it diagnosed?
• Have you or has anyone in your family ever been diagnosed with multiple endocrine neoplasia, type 1?
• Have you or has anyone in your family been diagnosed with parathyroid, thyroid or pituitary problems?
• Have you ever been told you have high blood calcium?