Zollinger-Ellison syndrome

Zollinger-Ellison syndrome is a complex condition in which one or more tumors form in your pancreas or in the upper part of your small intestine (duodenum). These tumors secrete large amounts of a hormone that causes excessive production of acid by your stomach. The excess acid, in turn, leads to peptic ulcers.
The disease may occur at any time in life, but the average age at diagnosis is 50.
Treatment for Zollinger-Ellison syndrome most often consists of medications to reduce acid and heal the ulcers. Surgery to remove the tumors may be an option for some people with Zollinger-Ellison syndrome.

The exact cause of Zollinger-Ellison syndrome remains unknown. Pancreas, duodenum and stomach But the sequence of events that occurs in Zollinger-Ellison syndrome is clear. The syndrome begins when a tumor (gastrinoma) or tumors form in your pancreas or duodenum.
Your pancreas is located behind and below your stomach. It produces enzymes that are essential to digesting food. The pancreas also produces several hormones, including insulin and glucagon, both of which regulate blood sugar levels, as well as the stomach hormone gastrin, which controls production of stomach acid. The duodenum, the upper part of the small intestine, begins at the lower end of your stomach. In the duodenum, digestive juices from the pancreas, liver and gallbladder mix, and digestion reaches its peak.
The tumors that occur with Zollinger-Ellison syndrome are made up of cells that secrete very large amounts of gastrin, which in turn cause the stomach to produce far too much acid. The excessive acid then leads to peptic ulcers and sometimes to diarrhea. In addition to causing excess acid production, the tumors may be cancerous (malignant). The tumors themselves grow slowly, but the cancer can spread elsewhere — most commonly to nearby lymph nodes or your liver.

Zollinger-Ellison syndrome may be associated with another disease called multiple endocrine neoplasia, type 1 (MEN 1). People with MEN 1 have multiple tumors in the endocrine system in addition to pancreatic tumors. They also have tumors in the parathyroid glands and may have tumors in their pituitary glands. About 25 percent of people who have gastrinomas have them as part of MEN 1.

Although your symptoms may prompt you to visit your primary care physician, he or she will likely refer you to a gastroenterologist to diagnose this rare disorder, or for treatment. You may also be referred to an oncologist, a doctor who specializes in treating cancer.

Because appointments can be brief, and because there’s often a lot of ground to cover, it’s a good idea to be well prepared for your appointment. Here’s some information to help you get ready for your appointment, and what to expect from your doctor.

What you can do

  • Be aware of any pre-appointment restrictions. At the time you make the appointment, let your doctor’s staff know if you take any medications. Certain acid-reducing drugs, such as proton pump inhibitors, can alter the results of some tests used to diagnose Zollinger-Ellison syndrome.  However, don’t stop taking these medications without consulting your physician.
  • 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, be sure to write down what you know about your family’s medical history.
  • Bring a list of all medications, as well as any vitamins or supplements, that you’re taking.
  • Write down questions to ask your doctor.

Preparing a list of questions ahead of time will help you make the most of the limited time you have with your doctor. For Zollinger-Ellison syndrome, some basic questions to ask your doctor include:

  • What is the most likely cause of my symptoms?
  • Other than Zollinger-Ellison syndrome, are there any other possible causes for my symptoms?
  • What tests do I need to confirm the diagnosis? How should I prepare for those tests?
  • What is the standard treatment for Zollinger-Ellison syndrome?
  • Are there any other options?
  • What course of action do you recommend?
  • Are there any dietary restrictions I need to follow?
  • Do I need to see a specialist? Will my insurance cover seeing a specialist?
  • Is there a generic alternative for the medication you’re prescribing for me?
  • Are there any Web sites that you recommend I visit to learn more about Zollinger-Ellison syndrome?
  • Are any other medical problems more likely to occur because I have Zollinger-Ellison syndrome?
  • How often do I need to come back for follow-up appointments?

In addition to the questions that you’ve prepared, don’t hesitate to ask additional questions during your appointment or ask your doctor to clarify something that you don’t understand.

What to expect from your doctor
Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over any points you want to spend more time on. Your doctor may ask:

  • When did you first begin experiencing symptoms?
  • Have your symptoms been continuous, or do they come and go?
  • How severe are your symptoms?
  • What, if anything, improves your symptoms?
  • What, if anything, worsens your symptoms?
  • Have you ever been told you have a stomach ulcer? How was it diagnosed?
  • Have you or anyone in your family ever been diagnosed with multiple endocrine neoplasia, type 1?
  • Have you or anyone in your family been diagnosed with parathyroid, thyroid or pituitary problems?
  • Have you ever been told you have high blood calcium?

Tests and diagnosis

Besides reviewing your medical history and asking about your signs and symptoms, your doctor may recommend the following diagnostic procedures:

  • Blood tests. A sample of your blood is analyzed in a laboratory to see whether you have an increased gastrin level in your blood. An elevated gastrin level may indicate tumors in your pancreas or duodenum. This test needs to be done on an empty stomach, so you’ll have to fast prior to this test. Also, you may need to stop taking any acid-reducing medications to get the most accurate measure of your gastrin levels. Additionally, because gastrin levels can fluctuate, this test will likely need to be repeated at least three times.

    Elevation of gastrin can also occur if the stomach doesn’t make acid, which can occur if you have chronic inflammation of the stomach or have had surgery on your stomach. This condition can be confused with Zollinger-Ellison because gastrin levels can get quite high. Your doctor may test the acidity of the stomach to clarify which condition is elevating your gastrin levels. If the stomach isn’t acidic, then Zollinger-Ellison is unlikely. If your stomach makes acid, your doctor may perform a secretin stimulation test. For this test, your doctor measures your gastrin levels, and then gives you an injection of the hormone secretin. Another measurement of gastrin levels is then taken. If you have Zollinger-Ellison, your gastrin levels will increase even more.

  • Upper gastrointestinal endoscopy. After you’ve been 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 for examination in the laboratory to help detect the presence of gastrin-producing tumors. To prepare for the test, your doctor will ask you not to eat anything after midnight the night before the test.
  • Imaging studies. In order to pinpoint the location of tumors, your doctor may use imaging techniques such as a nuclear scan — which uses radioactive tracers to help locate tumors — computerized tomography (CT), ultrasound imaging, or magnetic resonance imaging (MRI).
  • Endoscopic ultrasound. In this procedure, your doctor examines your stomach and duodenum with an endoscope fitted with an ultrasound probe. The probe allows closer imaging of the digestive tract, 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.

Treatments and drugs

In treating Zollinger-Ellison syndrome, doctors focus first on the tumors and then on the ulcers.

Treatment of tumors
An operation to remove the tumors that occur in Zollinger-Ellison requires great skill 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)
  • A liver transplant
  • 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

More radical surgical approaches, such as severing the nerves that promote acid secretion or removing the entire stomach, aren’t generally done today because medications are usually successful in controlling acid production and ulcers.

Treatment of excess acid
Today, excess acid production can almost always be controlled. Medications known as proton pump inhibitors are the first line of treatment. These are the most 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), pantaprazole (Protonix), rabeprazole (Aciphex), and esomeprazole magnesium (Nexium).

Previously, medications called histamine (H-2) blockers were used, but these medications don’t work as well as proton pump inhibitors do in treating the ulcers of Zollinger-Ellison syndrome.

Your doctor may also suggest one of several operations to treat peptic ulcers. This may include surgery to:

  • Stop an ulcer from bleeding
  • Relieve an obstruction caused by an ulcer
  • Close up the hole (perforation) that an ulcer has made in the wall of your stomach or duodenum