Zollinger-Ellison Syndrome

What is it? Zollinger-Ellison Syndrome

Zollinger-Ellison Syndrome (ZES) is the presence of symptoms caused by increased gastrin production. The most common cause is the development of neuroendocrine tumors located outside the stomach

About the Disease
The main diagnostic criteria for ZES are:

increased acidity of gastric juice with almost unchanged pepsin secretion;
recurring peptic ulcers in the gastroduodenal zone, associated with focal formation in the pancreas, without leading to an increase in blood insulin levels;
recurring abdominal pain of various localization, mainly in the upper abdomen.
However, not all cases always have all three signs simultaneously.
Symptoms may include nausea, vomiting, sharp abdominal pains in all areas, and loose stools. These manifestations are nonspecific, so the suspicion of Zollinger-Ellison syndrome is raised by frequent recurrences of complications despite anti-ulcer therapy. Determining the level of gastrin in the blood is used in differential diagnosis (in gastrinoma, it is significantly elevated). Instrumental examinations are also conducted to visualize tumor tissue.

Treatment of the syndrome is aimed at removing the tumor. If pathological formation cannot be detected by modern visualization methods, drug therapy is carried out to reduce hydrochloric acid production.

Symptoms of Zollinger-Ellison Syndrome

Symptoms of Zollinger-Ellison Syndrome in adults may include constant epigastric pain, occurring regardless of food intake. This syndrome is also characterized by the formation of multiple non-healing ulcers in the gastroduodenal zone, small intestine, and dysfunction of adjacent organs of the digestive tract.
Manifestations of Zollinger-Ellison Syndrome depend on the nature of peptic ulcer disease (complicated and uncomplicated forms). Most patients without complications experience varying degrees of epigastric pain, which is often constant but can be intermittent. Increased acidity leads to heartburn and regurgitation, and sometimes vomiting of acidic contents. The stool character also changes, which is associated with pancreatic insufficiency. Diarrhea with a large amount of fecal matter, often containing a significant admixture of fat particles, is typical. Over time, anemia develops, the protein level in the blood decreases, leading to progressive weight loss and deterioration of the general condition.
Sometimes, secondary damage to the pancreas may come to the forefront in Zollinger-Ellison Syndrome. This includes encircling pain, steatorrhea, nausea and vomiting, loose stools, flatulence, and weight loss. Secondary involvement of the colon with the development of constipation may also occur. This once again underscores the importance of step-by-step and comprehensive examination of patients with the identification of direct and indirect signs of the disease.

Causes of Zollinger-Ellison Syndrome

The causes of Zollinger-Ellison Syndrome are considered to be the appearance of an additional pool of cells secreting gastrin in the body. Usually, this proliferation occurs in the exocrine part of the pancreas. However, not every focal formation secretes gastrin. If the tumor originates from beta cells, insulinoma develops, which is not characteristic of Zollinger’s syndrome (the main manifestations are associated with excess insulin).
Gastrinomas usually occur spontaneously and are not associated with a family history of the disease. In some patients, they may be a manifestation of multiple endocrine neoplasia syndrome type 1.


Zollinger-Ellison Syndrome is divided into 2 categories:
tumor-associated elevation of gastrin levels;
non-tumor-associated variant associated with changes in the activity of gastric parietal cells (they synthesize gastrin).

Diagnosis of Zollinger-Ellison Syndrome

Zollinger-Ellison Syndrome should be considered in all cases of recurrent ulceration in the gastroduodenal zone despite conservative treatment of peptic ulcer disease or in patients who have undergone surgical removal of part of the stomach. The likelihood of this syndrome also increases when ulcers are located in the portion of the duodenum adjacent to the jejunum.

According to clinical recommendations, the diagnosis of Zollinger-Ellison Syndrome begins with determining the concentration of gastrin in the blood. Markedly elevated levels of this hormone are characteristic of gastrinoma. However, for differential diagnosis, it is also recommended to determine the level of gastric acid secretion in response to histamine injection. In ZES, this indicator remains almost unchanged.

The next stage of examination is the topographic detection of the tumor. Ultrasound, computed tomography, and magnetic resonance imaging are performed.

Differential diagnosis of Zollinger-Ellison Syndrome is conducted with the following conditions, in which gastrin concentration in the blood may also increase:
chronic inflammation of the gastric mucosa;
malignant tumor of the stomach;
adrenal tumor secreting adrenaline and noradrenaline (pheochromocytoma);
post-vagotomy status;
narrowing of the gastric outlet;
increased activity of parietal cells in the antral part of the stomach (due to their increased number or increased functional activity with a normal count);
short bowel syndrome.

Treatment of Zollinger-Ellison Syndrome

Etiological Treatment:
The etiological treatment of Zollinger-Ellison Syndrome is surgery to remove the neuroendocrine tumor.

Conservative Treatment:
In the preoperative period, as well as in cases where it is impossible to determine the localization of the neuroendocrine tumor, the use of proton pump inhibitors is recommended. These drugs suppress the formation of hydrochloric acid in the stomach, reducing the acidity level and thus eliminating conditions for the formation of epithelial defects in the mucosa. Conservative therapy is effective if it alleviates pain and normalizes stool characteristics. Iron supplements are also included in the therapy if hemoglobin levels decrease.

Surgical Treatment:
The classic surgery for this condition is the removal of the gastrin-producing tumor. The excised tissue is sent for histological examination to exclude malignant processes.