Zollinger-Ellison syndrome

Date Updated: 10/14/2020

Overview

Zollinger-Ellison syndrome is a rare condition in which one or more tumors form in your pancreas or the upper part of your small intestine (duodenum). These tumors, called gastrinomas, secrete large amounts of the hormone gastrin, which causes your stomach to produce too much acid. The excess acid then leads to peptic ulcers, as well as to diarrhea and other symptoms.

Zollinger-Ellison syndrome may occur at any time in life, but people usually find out they're affected between ages 20 and 60. Medications to reduce stomach acid and heal the ulcers are the usual treatment for Zollinger-Ellison syndrome.

Symptoms

Signs and symptoms of Zollinger-Ellison syndrome may include:

Abdominal pain
Diarrhea
Burning, aching, gnawing or discomfort in your upper abdomen
Acid reflux and heartburn
Burping
Nausea and vomiting
Bleeding in your digestive tract
Unintended weight loss
Decreased appetite

When to see a doctor

See your doctor if you have a persistent, burning, aching or gnawing pain in your upper abdomen, especially if you've also been experiencing nausea, vomiting and diarrhea.

Tell your doctor if you've used over-the-counter acid-reducing medications such as omeprazole (Prilosec, Zegerid), cimetidine (Tagamet HB) or famotidine (Pepcid AC) for long periods of time. These medications may mask your symptoms, which could delay your diagnosis.

Causes

The exact cause of Zollinger-Ellison syndrome remains unknown. But the sequence of events that occurs in Zollinger-Ellison syndrome is clear. The syndrome begins when one or more tumors (gastrinomas) form in your pancreas or duodenum or at other sites such as the lymph nodes adjacent to your pancreas.

Your pancreas sits behind and below your stomach. It produces enzymes that are essential to digesting food. The pancreas also produces several hormones including insulin, a hormone that helps to control your blood glucose.

Digestive juices from the pancreas, liver and gallbladder mix in the duodenum, the part of the small intestine next to your stomach. This is where digestion reaches its peak.

The tumors that occur with Zollinger-Ellison syndrome are made up of cells that secrete large amounts of the hormone gastrin. Increased gastrin makes the stomach produce 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 (malignant). 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 and may have tumors in their pituitary glands.

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

Risk factors

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

Diagnosis

Your doctor will base a diagnosis on the following:

Medical history. Your doctor will ask about your signs and symptoms and review your medical history.
Blood tests. A sample of your blood is analyzed to see whether you have elevated gastrin levels. While elevated gastrin may indicate tumors in your pancreas or duodenum, it can also be caused by other conditions. For example, gastrin may also be elevated if your stomach isn't making acid, or you're taking acid-reducing medications, such as proton pump inhibitors.

You need to fast before this test and may need to stop taking any acid-reducing medications to get the most accurate measure of your gastrin levels. Because gastrin levels can fluctuate, this test may be repeated a few times.

Your doctor may also perform a secretin stimulation test. For this test, your doctor first measures your gastrin levels, then gives you an injection of the hormone secretin and measures gastrin levels again. If you have Zollinger-Ellison, your gastrin levels will increase even more.
Upper gastrointestinal endoscopy. After you're sedated, your doctor inserts a thin, flexible instrument with a light and video camera (endoscope) down your throat and into your stomach and duodenum to look for ulcers. Through the endoscope, your doctor may remove a tissue sample (biopsy) from your duodenum to help detect the presence of gastrin-producing tumors. Your doctor will ask you not to eat anything after midnight the night before the test.
Endoscopic ultrasound. In this procedure, your doctor examines your stomach, duodenum and pancreas with an endoscope fitted with an ultrasound probe. The probe allows for closer inspection, making it easier to spot tumors.

It's also possible to remove a tissue sample through the endoscope. You'll need to fast after midnight the night before this test, and you'll be sedated during the test.
Imaging tests. Your doctor may use imaging techniques such as 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 addresses the hormone-secreting tumors as well as the ulcers they cause.

Treatment of tumors

An operation to remove the tumors that occur in Zollinger-Ellison requires a skilled surgeon because the tumors are often small and difficult to locate. If you have just one tumor, your doctor may be able to remove it surgically, but surgery may not be an option if you have multiple tumors or tumors that have spread to your liver. On the other hand, even if you have multiple tumors, your doctor still may recommend removing a single large tumor.

In some cases, doctors advise other treatments to control tumor growth, including:

Removing as much of a liver tumor as possible (debulking)
Attempting to destroy the tumor by cutting off the blood supply (embolization) or by using heat to destroy cancer cells (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. Medications known as proton pump inhibitors are the first line of treatment. These are effective medications for decreasing acid production in Zollinger-Ellison syndrome.

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

Long-term use of prescription proton pump inhibitors, especially in people age 50 and older, has been associated with an increased risk of fractures of the hip, wrist and spine, according to the Food and Drug Administration. This risk is small and should be weighed against the acid-blocking benefits of these medications.

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

Preparing for an appointment

Although your symptoms may prompt you to visit your primary care doctor, you'll likely be referred to a doctor who specializes in diseases of the digestive system (gastroenterologist) to diagnose and treat Zollinger-Ellison syndrome. You may also be referred to an oncologist, a doctor who specializes in treating cancer.

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

What you can do

Be aware of any pre-appointment restrictions. When you make the appointment, let your doctor's staff know if you take any medications. Certain acid-reducing drugs, such as proton pump inhibitors or H-2 antagonists, can alter the results of some tests used to diagnose Zollinger-Ellison syndrome. However, don't stop taking these medications without consulting your doctor.
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 doctor.

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 doctor 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?