What is Zollinger-Ellison Syndrome & How is it Treated?

What is Zollinger-Ellison Syndrome (ZES)?

Zollinger-Ellison Syndrome (ZES) is a rare condition that tends to affect the pancreas and the upper part of the small intestine, known as the duodenum. (1,2,3) The syndrome causes one or more tumors to develop in the digestive tract. These tumors are known as gastrinomas, and they secrete large amounts of the gastrin hormone. The hormone gastrin triggers an overproduction of gastric acid. While your body requires some amount of gastric acid to help in the breakdown and digestion of food, but too much of acid can lead to the formation of ulcers, diarrhea, and many other symptoms. It is possible to have only one tumor, though it is more common to develop multiple tumors. Nearly half of these tumors, though, are benign or non-cancerous. (4,5)

People with Zollinger-Ellison syndrome are at a higher risk of developing peptic ulcers as compared to people who don’t have this condition. Peptic ulcers are painful sores that form in the lining of the digestive tract. (6,7)

A person may be inflicted with Zollinger-Ellison syndrome at any point in their life, but people usually get affected between the ages of 20 and 60 years. Medications that help heal the ulcers and reduce the production of stomach acid are the standard treatments for Zollinger-Ellison syndrome.

Zollinger-Ellison syndrome is an extremely rare condition, and it only occurs in around 1 in 1 million people. It is more commonly observed in women than men and affects people between the ages of 20 and 50. (8)

What are the Symptoms of Zollinger-Ellison syndrome?

Symptoms of Zollinger-Ellison syndrome are usually related to the digestive system. The two most common symptoms are diarrhea and abdominal pain. (9) Other symptoms of Zollinger-Ellison syndrome may include:

  • Loss of appetite
  • Burping
  • Bloating
  • Acid reflux and heartburn
  • Nausea
  • Vomiting, which may have traces of blood in it if there are peptic ulcers
  • Bleeding in the digestive tract
  • Aching, burning, discomfort, or gnawing in the upper abdomen
  • Weight loss for no known reason

The symptoms of Zollinger-Ellison syndrome can be easily confused with the more common condition of gastroesophageal reflux disease (GERD) or peptic ulcer disease. Gastroesophageal reflux disease is a chronic condition that causes the stomach acid to backflow into the esophagus. The symptoms of Zollinger-Ellison syndrome, though, are more severe than these other digestive conditions and are also less responsive to the conventional treatments used to treat these other disorders. (10)

What are the causes of Zollinger-Ellison syndrome?

The exact cause of Zollinger-Ellison syndrome is not really known. In most cases, this disorder seems to develop for no clear reason. In 25 % of the cases, it is linked with an inherited tumor-causing condition known as multiple endocrine neoplasia type 1 (MEN1). (11,12) People with MEN1 are also known to have tumors in their parathyroid glands, and some even have tumors growing in their pituitary glands. If you have a parent or sibling with MEN1, it increases the risk that you may have Zollinger-Ellison syndrome. However, more research is needed to understand this link better.

Nevertheless, the sequence of events that occurs in people who have Zollinger-Ellison syndrome has been extensively researched. The syndrome starts when one or more gastrinomas form in the pancreas or the duodenum. They may even develop at other sites, such as the lymph nodes located next to the pancreas. (13)

The pancreas is located just behind and below the stomach. It manufactures enzymes that are necessary for digesting food. The pancreas is also responsible for the production of several hormones, including insulin, which is an essential hormone that helps regulate blood glucose in the body.

Digestive juices released from the pancreas, gallbladder, and liver mix in the duodenum, which is the part of the small intestine that sits right next to the stomach. This is the place where the process of digestion reaches its peak.

The tumors that develop with Zollinger-Ellison syndrome are made up of cells that release large amounts of gastrin. This increased gastrin makes the stomach overproduce gastric acid, which can lead to the formation of peptic ulcers and cause the symptoms of Zollinger-Ellison syndrome.

Apart from causing excessive production of gastric acid, the tumors can be cancerous or malignant. Though the tumors tend to grow slowly, but the cancer can spread to other parts of the body, especially to the liver or nearby lymph nodes. (14)

How is Zollinger-Ellison Syndrome Diagnosed?

If your doctor suspects that you may have Zollinger-Ellison syndrome, they will prescribe various diagnostic tests, including a blood test to check if the levels of gastrin are elevated. You will be required to fast before this blood test and will also need to stop taking any type of acid-reducing medications so as that the most accurate measure of gastrin levels can be determined through the test. If the blood test results show that gastrin levels are elevated, your doctor will further order imaging tests to determine the exact size and location of the gastrinomas or tumors. These tests may include the following: (15)

  • MRI scan
  • CT scan
  • Endoscopic ultrasound that will involve inserting a thin ultrasound probe down your throat.

In the case of endoscopic ultrasound, your throat will first be numbed with a liquid anesthetic, or you may even be administered light sedation in an outpatient procedure room. An upper gastrointestinal endoscopy may also be done to collect tissue samples to check for gastrinomas. (16,17)

What is the Treatment for Zollinger-Ellison Syndrome?

There are a variety of treatments used for Zollinger-Ellison syndrome. The exact treatment that your doctor will recommend depends on many factors, including the severity of your condition and symptoms. Some of the commonly prescribed treatment for Zollinger-Ellison syndrome include:

  • Proton Pump Inhibitors: Your doctor is likely to prescribe you a class of drugs known as proton pump inhibitors. These medicines are used to help lower the amount of gastric acid that is being produced by the body. This can help the peptic ulcers heal. These drugs are usually administered in very high doses to people with Zollinger-Ellison syndrome than to people who have peptic ulcers but no gastrinomas. While you are on the proton pump inhibitors, you will need to be carefully monitored. Long-term use of proton pump inhibitors, though, can increase the risk of spine, write, and hip fractures, especially if you are over the age of 50. (18,19)
  • Octreotide (brand name Sandostatin), a medication similar to the somatostatin hormone, may also be prescribed to certain people to counteract the impact of gastrin. (20)
  • Surgery: In some cases of Zollinger-Ellison syndrome, you might need to undergo surgery to remove the tumors. However, surgery can be a complicated procedure since many of the gastrinomas are small, difficult to locate, and can be present in multiples. In the case of people with Zollinger-Ellison syndrome, the tumor removing surgery has to be done by a very skilled surgeon due to the minuscule size of the tumors. If you have just one tumor, your doctor may remove it surgically, but in the case of multiple tumors or tumors that have already spread to the liver, then surgery may no longer be an option. Sometimes, even if you have several tumors, your doctor might still decide to go ahead and remove a single large tumor. Nevertheless, your doctor may also recommend some other treatments to control the growth of gastrinomas, such as:
    • A procedure known as debulking, which involves removing as much of a tumor on the liver as possible. (21)
    • Attempt to destroy the tumor by cutting off its blood supply, a procedure known as embolization, or by using radiofrequency ablation, which uses heat to destroy the cancer cells. (22,23)
    • Injecting drugs directly into the tumor to relieve the cancer symptoms.
    • Chemotherapy to slow down the growth of the tumors.
    • Having a liver transplant.

Conclusion: What is the Outlook for Zollinger-Ellison syndrome?

Zollinger-Ellison syndrome is a rare but serious medical condition. It is important to know that most Zollinger-Ellison syndrome tumors grow at a slow rate, and medications can be very effective in reducing any ulcer pain and also reducing the production of gastric acid. If you are experiencing digestive problems like heartburn, diarrhea, or any abdominal pain that lasts for over a few days, you should make it a point to consult a doctor. Getting an early diagnosis and starting treatment early can help stop the spread of any cancerous tumors to other parts of the body.

References:

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  3. Isenberg, J.I., Walsh, J.H. and Grossman, M.I., 1973. Zollinger-Ellison syndrome. Gastroenterology, 65(1), pp.140-165.
  4. Epelboym, I. and Mazeh, H., 2014. Zollinger-Ellison syndrome: classical considerations and current controversies. The oncologist, 19(1), p.44.
  5. MSD Manual Consumer Version. 2021. Gastrinoma – Digestive Disorders – MSD Manual Consumer Version. [online] Available at: <https://www.merckmanuals.com/home/digestive-disorders/tumors-of-the-digestive-system/gastrinoma> [Accessed 17 April 2021].
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  7. Meko, MD, J.B. and Norton, MD, J.A., 1995. Management of patients with Zollinger-Ellison syndrome. Annual review of medicine, 46(1), pp.395-411.
  8. Information, H., Diseases, D., Syndrome, Z. and Syndrome, Z., 2021. Zollinger-Ellison Syndrome | NIDDK. [online] National Institute of Diabetes and Digestive and Kidney Diseases. Available at: <https://www.niddk.nih.gov/health-information/digestive-diseases/zollinger-ellison-syndrome> [Accessed 17 April 2021].
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  11. NORD (National Organization for Rare Disorders). 2021. Zollinger-Ellison Syndrome – NORD (National Organization for Rare Disorders). [online] Available at: <https://rarediseases.org/rare-diseases/zollinger-ellison-syndrome/> [Accessed 17 April 2021].
  12. Gibril, F., Schumann, M., Pace, A. and Jensen, R.T., 2004. Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine, 83(1), pp.43-83.
  13. Benya, R.V., Metz, D.C., Venzon, D.J., Fishbeyn, V.A., Strader, D.B., Orbuch, M. and Jensen, R.T., 1994. Zollinger-Ellison syndrome can be the initial endocrine manifestation in patients with multiple endocrine neoplasia-type I. The American journal of medicine, 97(5), pp.436-444.
  14. Creutzfeldt, W., Arnold, R., Creutzfeldt, C. and Track, N.S., 1975. Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome). Human Pathology, 6(1), pp.47-76.
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  17. Norton, J.A., Melcher, M.L., Gibril, F. and Jensen, R.T., 2004. Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment. Surgery, 136(6), pp.1267-1274.
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