Zollinger-Ellison syndrome (ZES) is caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration. ZES may occur sporadically or as part of an autosomal dominant familial syndrome, multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the duodenum, the pancreas, and abdominal lymph nodes, but ectopic locations have also been described (eg, heart, ovary, gall bladder, liver, kidney).
The symptoms of Zollinger-Ellison syndrome (ZES) are secondary to hypergastrinemia, which causes hypertrophy of the gastric mucosa, leading to increased numbers of parietal cells and increased maximal acid output. Gastrin by itself also stimulates acid secretion, resulting in increased basal acid secretion. The large quantity of acid produced leads to gastrointestinal mucosal ulceration. It also leads to diarrhea and malabsorption.
Malabsorption in ZES usually is multifactorial, being caused by direct mucosal damage by acid, inactivation of pancreatic enzymes, and precipitation of bile salts. ZES is sporadic in 75% of patients, whereas in the other 25% it is associated with MEN 1, an autosomal dominant condition characterized by hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors.
Zollinger-Ellison syndrome (ZES) is caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration.
ZES may occur sporadically or as part of multiple endocrine neoplasia-type 1 (MEN 1).
United States statistics
Zollinger-Ellison syndrome (ZES) occurs in approximately 0.1-1% of all patients with duodenal ulcers. Its frequency of occurrence is reported to be approximately the same as insulinoma, the most common functioning pancreatic endocrine tumor.
Race-, sex-, and age-related demographics
All races can be affected.
A slight male predominance exists, with a male-to-female ratio of 1.3:1.
The mean age of onset of ZES is 43 years; however, patients with multiple endocrine neoplasia-type 1 and ZES (MEN 1/ZES) present a decade earlier. Generally, a 5- to 7-year delay in diagnosis occurs. In a prospective study, fewer than 3% of patients were younger than 20 years, whereas 7% were older than 60 years at the time of disease onset.
Incidence is 1-3 cases per million patients per year in Sweden, 0.5 cases per million patients per year in Ireland, and 0.1-0.2 cases per million patients per year in Denmark.
Prognosis is excellent in patients with Zollinger-Ellison syndrome (ZES) without metastatic disease.
Currently, the morbidity and mortality of ZES is low because of improved medical and surgical management of the disease. Fewer than 5% of patients develop a complication, such as abdominal perforation, gastric outlet obstruction, or esophageal stricture.
The following complications may arise in patients with ZES:
Abdominal perforation secondary to ulceration (The duodenum and jejunum are the most common sites.)
Esophageal stricture, with reflux
Gastric carcinoids (especially in patients with multiple endocrine neoplasia-type 1 [MEN 1])