Zollinger-Ellison Syndrome

The Zollinger-Ellison syndrome is caused by a gastrin-producing tumor, usually located in the pancreas or duodenal wall. The result is gastric hypersecretion and peptic ulcer. The diagnosis is established when determining the levels of gastrin. Treatment of Zollinger-Ellison syndrome consists in prescribing proton pump inhibitors and surgical removal of the tumor.

The disease, characterized as a triad of symptoms - gastric hypersecretion, recurrent gastro-duodenal ulcer resistant and non-insulin-producing pancreatic tumor - was first described in 1955 by RM Zollinger and EN Ellison. Since then it is called Zollinger-Ellison syndrome. A similar clinical picture gives hyperplasia of the G cells of the mucous membrane of the antral stomach and a gastrin-producing pancreatic tumor (less often the tumor of the stomach, duodenum). The gastrin producing tumor is also called gastrinoma.

ICD-10 code

E16.8 Other specified disorders of internal secretion of the pancreas.

The classification of Zollinger-Ellison syndrome is not developed. To determine the tactics of treatment, it is extremely important to divide gastrin into malignant and benign.

Epidemiology of the Zollinger-Ellison syndrome

In the USA, the frequency of Zollinger-Ellison syndrome is estimated as 0.1-1% of all patients with peptic ulcer. Nevertheless, these data are also underestimated, since the characteristic clinical symptomatology of peptic ulcer or NSAID-mediated lesions of the gastrointestinal tract often leads the clinician away from a special examination of the patient for the diagnosis of Zollinger-Ellison syndrome. Usually gastrinomas are detected at the age of 20-50 years, somewhat more often in men (1.5-2: 1).

[1], [2], [3], [4]

What causes Zollinger-Ellison syndrome?

Gastrinomas develop in the pancreas or duodenal wall in 80-90% of cases. In other cases, the tumor can be localized in the spleen gates, intestinal mesentery, stomach, lymph node or ovary. Approximately 50% of patients have multiple tumors. Gastrinomas are usually of small size (less than 1 cm in diameter) and grow slowly. Approximately 50% of them are malignant. About 40-60% of patients with gastrinomas suffer from multiple endocrine neoplasia.

Pathogenesis of Zollinger-Ellison syndrome

Symptoms of Zollinger-Ellison syndrome

Zollinger-Ellison syndrome is usually manifested by the aggressive course of peptic ulcer disease, ulcers developing in atypical sites (up to 25% distal to the bulb of the duodenum). However, 25% have no ulcer diagnosis. Characteristic symptoms of ulcers and complications (eg, perforation, bleeding, stenosis) may develop. Diarrhea is one of the initial signs in 25-40% of patients.

Symptoms of Zollinger-Ellison syndrome

Diagnosis of Zollinger-Ellison syndrome

The Zollinger-Ellison syndrome can be suspected after an anamnesis, especially if the symptoms remain unresponsive to standard antiulcer therapy.

The most reliable test is to determine serum gastrin level. In all patients, levels are greater than 150 pg / ml; significantly elevated levels of more than 1000 pg / ml in patients with appropriate clinical manifestations and increased gastric secretion greater than 15 mEq / h allow diagnosis. However, moderate hypergastrinemia can be observed in the state of hypochlorhydria (eg, pernicious anemia, chronic gastritis, use of proton pump inhibitors), with renal insufficiency with reduced gastrin clearance, with extensive bowel resection and pheochromocytoma.

Provocative test with secretin can be used in patients with gastrin levels less than 1000 pg / ml. Intravenously, a secretin solution is injected in a dose of 2 μg / kg with a sequential measurement of the serum gastrin level (10 and 1 minute before and 2.5,10,15, 20 and 30 minutes after administration). A characteristic response to gastrinoma is an increase in gastrin levels, unlike G-cell hyperplasia of the antrum or a typical peptic ulcer. Patients also need to perform studies on Helicobacter pylori infection , which usually leads to peptic ulcers and a modest increase in gastrin secretion.

When establishing the diagnosis, it is necessary to verify the localization of the tumor. Initial study - CT of the abdominal cavity or somatostatin receptor scintigraphy, which allows to identify the primary tumor and metastatic disease. Also selective arteriography with image enhancement and subtraction is effective. If there are no signs of metastasis and preliminary studies are questionable, endoscopic ultrasound is performed . As an alternative, selective arterial administration of secretin.

Diagnosis of Zollinger-Ellison syndrome

[5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]

Treatment of Zollinger-Ellison syndrome

With an isolated tumor and surgical treatment, the survival of 5-10 years is more than 90% compared to 43 and 25%, respectively, with incomplete removal of the tumor.

Inhibition of acid production

Proton pump inhibitors are the drugs of choice: omeprazole or esomeprazole orally 40 mg 2 times a day. The dose can be gradually reduced when resolving the symptoms and reducing acid production. A maintenance dose is necessary; patients should take these drugs indefinitely, unless they undergo surgical treatment.

Injections of octreotide 100-500 mcg subcutaneously 2-3 times a day also allow to reduce gastric secretion and can be an alternative treatment method with ineffectiveness of proton pump inhibitors. Prolonged form of octreotide 20-30 mg intramuscularly can be used once a month.

Surgery

Surgical removal is indicated to patients without obvious signs of metastasis. During the operation, duodenotomy and endoscopic transillumination or intraoperative ultrasound can localize the tumor. Surgical treatment is possible in 20% of patients if gastrinoma is not part of the multiple endocrine neoplastic syndrome.

Treatment and prognosis of Zollinger-Ellison syndrome

Chemotherapy

In patients with metastatic disease, privileged chemotherapy for islet cell tumors is the use of streptozotocin in combination with 5-fluorouracil or doxorubicin. This treatment can reduce the tumor volume (50-60%), reduce gastrin levels and is an effective supplement to omeprazole. Unfortunately, chemotherapy does not cure patients with metastatic disease.

[16], [17], [18], [19], [20], [21], [22], [23]