Definition of Zollinger-Ellison syndrome
Zollinger-Ellison syndrome is a complex 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, in turn, leads to peptic ulcers.
Zollinger-Ellison syndrome (ZES) is rare. The disease may occur at any time in life, but people are usually diagnosed between ages 30 and 50. Medications to reduce stomach acid and heal the ulcers is the usual treatment for Zollinger-Ellison syndrome.
Symptoms of Zollinger-Ellison syndrome
Signs and symptoms of Zollinger-Ellison syndrome may include:
- Abdominal pain
- Burning, aching, gnawing or discomfort in your upper abdomen
- Acid reflux and heartburn
- 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), cimetidine (Tagamet), famotidine (Pepcid) or ranitidine (Zantac) for long periods of time. These medications may mask your symptoms, which could delay your diagnosis. If you have Zollinger-Ellison syndrome, early detection and treatment are important.
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 a tumor (gastrinoma) or tumors form in your pancreas, duodenum or 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 gastrin, a hormone that controls stomach acid production. 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 gastrin, which in turn causes the stomach to produce far too much acid. The excessive acid then leads to peptic ulcers and sometimes to diarrhea.
Besides 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.
Association with MEN I
Zollinger-Ellison syndrome may be caused by an inherited condition called multiple endocrine neoplasia, type I (MEN I). People with MEN I 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 I.
Preparing for your appointment
Although your symptoms may prompt you to visit your family doctor or a general practitioner, 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 also may 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, 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 is likely causing my symptoms or condition?
- 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 dietary restrictions I need to follow?
- 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?
- How often do I need to come back for follow-up appointments?
- What’s my prognosis?
What to expect from your doctor
Your doctor is likely to ask you a number of questions, including:
- When did you 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 has anyone in your family ever been diagnosed with multiple endocrine neoplasia, type I?
- 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?
Tests and 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. If you have a blood relative, such as a sibling or parent, with MEN I, it’s more likely that you have Zollinger-Ellison syndrome.
- 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 also can be caused by other conditions. You’ll have 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.
- Gastrin level measurement. Since elevated gastrin levels can be caused by conditions other than Zollinger-Ellison, your doctor may test the acidity of the stomach to clarify which condition is elevating your gastrin levels. Gastrin levels also can be elevated if your stomach doesn’t make acid or if you’re taking medications that block acid. If your stomach is making acid, your doctor may perform a secretin stimulation test. For this test, your doctor measures your gastrin levels, 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 for examination 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. Your doctor may use imaging techniques such as a nuclear scan — which uses radioactive tracers to help locate tumors — CT, ultrasound or 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 inspection 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 treat the tumors as well as the ulcers. If your doctor can remove the tumors, then ulcer treatment may no longer be needed.
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
- A liver transplant
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
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, 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.
Your doctor may also suggest one of several operations to treat peptic ulcers, such as 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