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 called 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 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, while in the other 25% it is associated with MEN 1, an autosomal dominant condition characterized by hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors.
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.
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.
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.
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, with the patients with MEN 1/ZES presenting a decade earlier. Generally, a 5- to 7-year delay in diagnosis occurs. In a recent prospective study, fewer than 3% of patients were younger than 20 years, while 7% were older than 60 years at the time of disease onset.
A high index of clinical awareness is needed to make a diagnosis of ZES.
Abdominal pain is the most common symptom, present in 75% of patients. Typically, it is located in the upper abdomen and mimics that of peptic ulcer disease. This symptom is reported more frequently by men and patients with the sporadic form of ZES.
Of patients with ZES, 73% have diarrhea, and this is the most common symptom in patients who have MEN 1/ZES and in female patients.
The combination of diarrhea and abdominal pain is present in more than half the patients.
Heartburn is the third most common symptom, and this symptom mimics gastroesophageal reflux disease (GERD).
Other symptoms include nausea, vomiting, gastrointestinal bleeding, and weight loss. Gastrointestinal bleeding frequently is due to ulceration in the duodenum and is the presenting symptom in 25% of patients.
In patients in whom MEN 1/ZES is suspected, a history indicative of nephrolithiasis, hypercalcemia, and pituitary disorders should be sought. A family history of nephrolithiasis, hyperparathyroidism, and gastrinoma also may be present.
The findings of the physical examination may be normal.
Patients may be pale if presenting with gastrointestinal bleeding.
Jaundice may occur if the tumor compresses the common bile duct, although this presentation is very rare.
Epigastric tenderness may be present.
Dental erosions may be noted if symptoms consistent with GERD are present.
The presence of hepatomegaly suggests liver metastasis.
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 MEN 1.