Zollinger-Ellison Syndrome: Causes, Symptoms, and Modern Approaches to Treatment

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Nida Ali Safdar , Soha Jabeen , Essra Ali Safdar

Department of pharmacy Practice, Anwar uloom college of pharmacy, Hyderabad, TS-India

Corresponding Author Email: nidaalisafdar@gmail.com

DOI : https://doi.org/10.51470/APR.2024.03.01.17

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Introduction

Zollinger-Ellison Syndrome (ZES) is a rare but significant endocrine disorder characterized by the presence of gastrin-secreting tumors known as gastrinomas. These tumors lead to excessive production of gastric acid, resulting in severe gastrointestinal complications, including recurrent peptic ulcers and debilitating abdominal symptoms. First described in 1955 by Dr. Robert Zollinger and Dr. Edwin Ellison, the syndrome often presents a diagnostic challenge due to its varied symptoms and low prevalence. ZES can occur sporadically or as part of the hereditary condition known as multiple endocrine neoplasia type 1 (MEN 1) [1]. Understanding the causes, symptoms, and modern treatment strategies for ZES is crucial for healthcare professionals, as timely and effective management can significantly improve patient outcomes and quality of life [2].

Zollinger-Ellison syndrome is a rare disorder characterized by the development of one or more tumors, known as gastrinomas, in the upper portion of the small intestine or pancreas. These tumors produce excessive amounts of the hormone gastrin, which leads to an overproduction of stomach acid. As a result, individuals with this syndrome often experience peptic ulcers, along with a variety of gastrointestinal symptoms such as diarrhea and abdominal pain [3]. Although Zollinger-Ellison syndrome can affect individuals at any stage of life, it is most commonly diagnosed in people between the ages of 20 and 60.

Treatment typically involves medications aimed at reducing stomach acid and healing ulcers, while some patients may also require surgery to remove the tumors. Symptoms of Zollinger-Ellison syndrome can include stomach pain, diarrhea, burning sensations in the upper abdomen, heartburn, burping, vomiting, nausea, gastrointestinal bleeding, unintentional weight loss, and decreased appetite [4]. Proper management of the condition is essential for improving the quality of life for those affected.

Etiology

It is unknown what specifically causes Zollinger-Ellison syndrome. However, the sequence of events in Zollinger-Ellison syndrome usually follows the same pattern. The syndrome starts when one or more tumors develop in the duodenum, a section of the small intestine, or the pancreas. The part that is attached to your stomach is called the duodenum. Tumors can occasionally develop at other locations, such the lymph nodes next to your pancreas. The pancreas is situated beneath and behind the stomach. It produces the enzymes required for food digestion. Insulin is one of the several hormones produced by the pancreas. The hormone that aids in regulating blood sugar, often known as glucose, is insulin. The duodenum is where the pancreatic, liver, and gallbladder’s digestive juices combine. The majority of your digestion takes place here. The cells that produce the tumors associated with Zollinger-Ellison syndrome emit a lot of the hormone gastrin. They are sometimes called gastrinomas because of this. The stomach produces far too much acid when there is an increase in gastrin. Peptic ulcers and occasionally diarrhea are the results of the excess acid. In addition to producing too much acid, the tumors are frequently malignant. Even though the tumors usually develop slowly, the cancer might spread to other places, usually to your liver or adjacent lymph nodes. Connection to MEN 1 Multiple endocrine neoplasia, type 1 (MEN 1) is a hereditary disorder that may be the cause of Zollinger-Ellison syndrome. MEN 1 patients also develop parathyroid gland tumors. Additionally, they might develop pituitary gland tumors [5]. MEN 1 is responsible for about 25% of gastrinoma cases. In addition, they might have pancreatic and other organ malignancies. The following methods can be used to diagnose a patient who is experiencing

Chronic diarrhea occurring alongside peptic ulcer disease or gastroesophageal disease (GED) can indicate underlying complex conditions. Peptic ulcer disease in these cases is often severe, recurrent, chronic, or associated with complications. Notably, some patients experience peptic ulcer disease without any history of nonsteroidal anti-inflammatory drug (NSAID) use or infection with Helicobacter pylori (H. pylori). Additionally, a family history of multiple endocrine neoplasia type 1 (MEN1) or its related symptoms may also be present, further suggesting a need for comprehensive evaluation [6].

Diagnostic Tests for Zollinger-Ellison Syndrome

Blood Tests 

To diagnose Zollinger-Ellison syndrome, your doctor may order blood tests that measure gastrin levels. A medical practitioner will draw blood and send the sample to a laboratory. Typically, these tests are done after fasting, where you may be asked to avoid eating for several hours, though drinking water is allowed. Elevated gastrin levels can be a sign of Zollinger-Ellison syndrome. Your doctor may also recommend a blood test after administering intravenous (IV) secretin—a hormone that stimulates gastrin production by gastrinomas—to further evaluate your gastrin levels. Prior to these tests, you may be advised to stop or adjust certain medications, particularly proton pump inhibitors (PPIs), as they can artificially raise gastrin levels [7].

Stomach Acid Test 

A stomach acid test may be prescribed to assess the pH, or acidity, of your stomach contents. In this test, a medical practitioner inserts a tube through your nose and down into your stomach to collect a fluid sample. Alternatively, pH levels can be measured during an upper gastrointestinal (GI) endoscopy. Additional tests may occasionally be performed to evaluate the amount of acid produced by your stomach [8].

Upper Gastrointestinal Endoscopy 

An upper GI endoscopy allows a physician to examine the lining of your upper gastrointestinal tract—specifically the esophagus, stomach, and duodenum—using an endoscope, a flexible tube with an attached camera. This procedure helps detect abnormalities associated with Zollinger-Ellison syndrome, including tumors and related complications. Your doctor may recommend this test to look for the tumors responsible for the syndrome as well as to monitor its impact on the GI lining [9].

Endoscopic retrograde cholangiopancreatography (ERCP): This procedure uses x-rays and upper Gl endoscopy to look at the pancreas and bile channels. Imaging examinations To assist identify the tumors that cause Zollinger-Ellison syndrome, doctors may prescribe imaging studies. Because small gastrinomas can be difficult to view, doctors may prescribe a variety of imaging tests, like as

Diagnostic Imaging and Treatments for Zollinger-Ellison Syndrome

Diagnostic Imaging 

Computed Tomography (CT): CT scans combine computer technology with X-rays to create detailed images of internal structures, aiding in locating gastrinomas.

Magnetic Resonance Imaging (MRI): MRI uses magnetic fields and radio waves, avoiding X-rays, to capture images of soft tissues and organs, providing an alternative method for gastrinoma visualization.

Radionuclide Scanning: A small amount of radioactive material is injected, and a specialized camera captures images that highlight areas of gastrinomas.

Endoscopic Ultrasonography: This technique uses an endoscope with an ultrasound device to produce images of internal organs, allowing precise visualization of gastrinomas within the gastrointestinal tract.

Angiography: During angiography, a physician inserts a catheter into major arteries and injects a dye visible on X-rays to outline blood vessels, helping to identify and assess tumors.

Treatment Options 

Proton Pump Inhibitors (PPIs): These medications, such as pantoprazole (Protonix), rabeprazole (Aciphex), lansoprazole (Prevacid), omeprazole (Prilosec, Zegerid), and esomeprazole (Nexium), reduce stomach acid production, providing relief from ulcers, diarrhea, and abdominal pain.

Surgery: Surgery to remove isolated gastrinomas may be recommended if the tumors have not spread to other organs.

Chemotherapy: In advanced cases where tumors have metastasized, chemotherapy may be used to target and destroy cancer cells.

Octreotide (Sandostatin): This medication can counteract the effects of excessive gastrin, offering symptom relief for some patients.

For patients without MEN1, doctors may recommend surgery to remove the tumors associated with Zollinger-Ellison syndrome. Removing these gastrinomas can sometimes prevent the tumors from spreading and help manage the syndrome. However, even after surgery, patients may still need proton pump inhibitors (PPIs) to control stomach acid levels. For individuals with MEN1, surgery is generally not advised to remove small gastrinomas, as these patients often have numerous tiny tumors that are difficult to locate and fully excise. However, if larger tumors are present—due to their higher likelihood of spreading—doctors may recommend surgical removal of these specific tumors [10].

Conclusion

Zollinger-Ellison Syndrome (ZES) is a rare but serious condition that arises from gastrin-producing tumors, or gastrinomas, primarily affecting the gastrointestinal tract and causing chronic acid hypersecretion. The clinical manifestations, including severe peptic ulcers, diarrhea, and abdominal pain, underscore the need for early diagnosis and targeted treatment. Advances in diagnostic techniques, such as imaging and biochemical tests, have improved the ability to identify and monitor gastrinomas, while treatments such as proton pump inhibitors and surgical interventions offer effective options for managing symptoms and improving patient outcomes. In cases associated with MEN1, careful assessment is required to balance surgical risks and benefits, given the complexity of tumor presentation. Continued research into pharmacological treatments, like octreotide, and genetic advancements hold promise for further improving ZES management and enhancing the quality of life for affected individuals.

References

• Mignon, M., & Bonfils, S. (1988). Diagnosis and treatment of Zollinger-Ellison syndrome. Baillière’s clinical gastroenterology, 2(3), 677-698.
• Rossi, R. E., Elvevi, A., Citterio, D., Coppa, J., Invernizzi, P., Mazzaferro, V., & Massironi, S. (2021). Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World journal of gastroenterology, 27(35), 5890.
• McCarthy, D. M. (1984). The diagnosis and treatment of gastrinoma and Zollinger-Ellison syndrome. In Diagnosis and management of endocrine-related tumors (pp. 347-382). Boston, MA: Springer US.
• Epelboym, I., & Mazeh, H. (2014). Zollinger-Ellison syndrome: classical considerations and current controversies. The Oncologist, 19(1), 44-50.
• Murugesan, S. V. M., Varro, A., & Pritchard, D. M. (2009). strategies to determine whether hypergastrinaemia is due to Zollinger–Ellison syndrome rather than a more common benign cause. Alimentary pharmacology & therapeutics, 29(10), 1055-1068.
• Mendelson, A. H., & Donowitz, M. (2017). Catching the zebra: clinical pearls and pitfalls for the successful diagnosis of Zollinger–Ellison syndrome. Digestive Diseases and Sciences, 62, 2258-2265.
• Albers, M. B., Manoharan, J., & Bartsch, D. K. (2019). Contemporary surgical management of the Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1. Best Practice & Research Clinical Endocrinology & Metabolism, 33(5), 101318.
• Moore, A. R., Varro, A., & Pritchard, M. (2012). Zollinger-Ellison syndrome. Gastrointestinal Nursing, 10(5), 44-49.
• Sostek, M. B., & Troiano, F. P. (2003). Zollinger-Ellison syndrome successfully treated with esomeprazole. Practical Gastroenterology, 27(5), 55-63.
• Konturek, S., Konturek, P. C., Bielański, W., Lorens, K., Sito, E., Konturek, J. W., & Stachura, T. (2002). Case presentation of gastrinoma combined with gastric carcinoid with the longest survival record: Zollinger-Ellison syndrome: pathophysiology, diagnosis and therapy. Medical Science Monitor, 8(6).