Zollinger-Ellison syndrome is a rare disorder that is usually caused by a gastrinoma, or tumor, that originates from the pancreas or, less likely, from the small intestine.The tumor secretes a hormone known as gastrin, and this results in an overproduction of hydrochloric acid in the stomach.
The syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin.The tumor causes excessive production of gastric acid, which leads to the growth of gastric mucosa and proliferation of parietal and ECL cells.ZES may occur on its own or as part of an autosomal dominant syndrome called multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the pancreas, duodenum or abdominal lymph nodes, but ectopic locations (e.g., heart, ovary, gallbladder, liver, and kidney) have also been described.
Causes of Zollinger–Ellison Syndrome
It is not clear exactly what causes Zollinger-Ellison syndrome, nor the gastrinomas that characterize it.
Gastrinomas release excessive quantities of gastrin, resulting in too much gastric acid in the stomach and duodenum. This eventually causes peptic ulcers to form in the lining of the duodenum. This often results in multiple ulcers that may cause pain or upper gastrointestinal bleeding.
As well as causing excess acid production, the gastrinomas may be malignant, or cancerous. The cancer can spread to other parts of the body, most commonly to nearby lymph nodes or the liver.Some cases of the syndrome are caused by a genetic disorder known as multiple endocrine neoplasia type 1, or MEN 1. MEN1 is a genetic syndrome that causes multiple endocrine cancers.
It is inherited in an autosomal dominant manner, which means that if a parent is affected, they have a 50 percent chance of passing the condition to the next generation.An individual may be at risk for developing a gastrinoma if they have had several family members with endocrine cancers, or if they have a family member with MEN1.
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 percent of people who have gastrinomas have them as part of MEN 1. They may have also have tumors in the pancreas and other organs.
Symptoms of Zollinger–Ellison Syndrome
The diagnosis is also suspected in patients who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment.
- Chronic diarrhea, including steatorrhea (fatty stools)
- Pain in the esophagus, especially between and after meals at night
- 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
- Vomiting blood
- Loss of appetite
- Bleeding from the stomach
- a person has peptic ulcers without the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen or a bacterial Helicobacter pylori (H. pylori)infection. NSAID use and H. pylori infection may cause peptic ulcers.
- a person has severe ulcers that bleed or cause holes in the duodenum or stomach.
- a health care provider diagnoses a person or the person’s family member with MEN1 or a person has symptoms of MEN1.
Gastrinomas may occur as single tumors or as multiple small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liverand to lymph nodes near the pancreas and small bowel.
Diagnosis of Zollinger–Ellison Syndrome
Zollinger–Ellison syndrome may be suspected when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or when endoscopy is suggestive. The diagnosis is made through several laboratory tests and imaging studies
- Secretin stimulation test, which measures evoked gastrin levels. Note that the mechanism underlying this test is in contrast to the normal physiologic mechanism whereby secretin inhibits gastrin release from G cells. Gastrinoma cells release gastrin in response to secretin stimulation,thereby providing a sensitive means of differentiation.
- Fasting gastrin levels on at least three separate occasions
- Gastric acid secretion and pH (normal basal gastric acid secretion is less than 10 mEq/hour; in Zollinger–Ellison patients, it is usually more than 15 mEq/hour)
- An increased level of chromogranin A is a common marker of neuroendocrine tumors.
- Endoscopic ultrasound – This procedure involves using a special endoscope called an endoechoscope to perform ultrasound of the pancreas. The endoechoscope has a built-in miniature ultrasound probe that bounces safe, painless sound waves off organs to create an image of their structure.
- Angiogram – An angiogram is a special kind of x ray in which an interventional radiologist—a specially trained radiologist—threads a thin, flexible tube called a catheter through the large arteries, often from the groin, to the artery of interest. The radiologist injects contrast medium through the catheter so the images show up more clearly on the x ray.
- Somatostatin receptor scintigraphy – An x-ray technician performs this test, also called Octreo Scan, at a hospital or an outpatient center, and a radiologist interprets the images. A person does not need anesthesia.
- Computerized tomography (CT) scan – A CT scan is an x ray that produces pictures of the body. A CT scan may include the injection of a special dye, called contrast medium. CT scans use a combination of x rays and computer technology to create images. CT scans require the person to lie on a table that slides into a tunnel-shaped device where an x-ray technician takes x rays.
- Magnetic resonance imaging (MRI) – MRI is a test that takes pictures of the body’s internal organs and soft tissues without using x rays. A specially trained technician performs the procedure in an outpatient center or a hospital, and a radiologist interprets the images. The person does not need anesthesia, though people with a fear of confined spaces may receive light sedation, taken by mouth.
In addition, the source of the increased gastrin production must be determined using MRI or somatostatin receptor scintigraphy.
Treatment of Zollinger–Ellison Syndrome
- Over-the-counter proton pump inhibitors — Proton pump inhibitors shut off the stomach’s acid production.Proton pump inhibitors are very effective. They can be especially helpful in patients who do not respond to H2 blockers and antacids. These drugs are more potent acid-blockers than are H2 blockers, but they take longer to begin their effect.
- Proton pump inhibitors – should not be combined with an H2 blocker. The H2 blocker can prevent the proton pump inhibitor from working.These are prescribed at higher doses than those available in over-the-counter forms.
- Motility drugs – These medications may help to decrease esophageal reflux. But they are not usually used as the only treatment for Zollinger-Ellison syndrome,. They help the stomach to empty faster, which decreases the amount of time during which reflux can occur.
- Mucosal protectors – These medications coat, soothe and protect the irritated esophageal lining. One example is sucralfate (Carafate).
- Antacids – Doctors often first recommend antacids to relieve heartburn and other mild GER and Zollinger-Ellison syndrome. Antacids include over-the-counter medicines such as. Antacids can have side effects, including diarrhea and constipation.
- H2 blockers – H2 blockers decrease acid production. They provide short-term or on-demand relief for many people with GER and Zollinger-Ellison syndrome,. They can also help heal the esophagus, although not as well as other medicines. You can buy H2 blockers over-the-counter or your doctor can prescribe one. Types of H2 blockers include
Proton pump inhibitors (PPIs) – PPIs lower the amount of acid your stomach makes. PPIs are better at treating Zollinger-Ellison syndrome (ZES) than H2 blockers. They can heal the esophageal lining in most people with . Doctors often prescribe PPIs for long-term Zollinger-Ellison syndrome (ZES) treatment. Such as
Prokinetics – Prokinetics help your stomach empty faster. Prescription prokinetics include
- bethanechol (Urecholine)
- metoclopramide (Reglan)
Both of these medicines have side effects, including
Prokinetics can cause problems if you mix them with other medicines, so tell your doctor about all the medicines you’re taking.
Health care providers sometimes use chemotherapy drugs to treat gastrinomas that cannot be surgically removed, including
Eating, Diet, and Nutrition
Researchers have not found that eating, diet, and nutrition play a role in causing or preventing Zollinger-Ellison syndrome.
Prevention of Zollinger–Ellison Syndrome
- Zollinger-Ellison syndrome is a rare disorder that occurs when one or more tumors form in the pancreas and duodenum.
- Experts do not know the exact cause of Zollinger-Ellison syndrome.
- About 25 to 30 percent of gastrinomas are caused by an inherited genetic disorder called multiple endocrine neoplasia type 1 (MEN1).
- Although anyone can get Zollinger-Ellison syndrome, the disease is more common among men 30 to 50 years old.
- Zollinger-Ellison syndrome signs and symptoms are similar to those of peptic ulcers.
- Some people with Zollinger-Ellison syndrome have only diarrhea, with no other symptoms. Others develop gastroesophageal reflux (GER).
A health care provider diagnoses Zollinger-Ellison syndrome based on the following
- medical history
- physical exam
- signs and symptoms
- blood tests
- upper gastrointestinal (GI) endoscopy
- imaging tests to look for gastrinomas
- measurement of stomach acid
- A health care provider treats Zollinger-Ellison syndrome with medications to reduce gastric acid secretion and with surgery to remove gastrinomas. A health care provider sometimes uses chemotherapy—medications to shrink tumors—when tumors are too widespread to remove with surgery.