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Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis

Emily Bergsland, MD
Section Editor
Mark Feldman, MD, MACP, AGAF, FACG
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Zollinger-Ellison (ZES) syndrome is characterized by gastric acid hypersecretion resulting in severe acid-related peptic disease and diarrhea [1,2]. The clinical manifestations and diagnosis of ZES will be reviewed here. The management of ZES is discussed separately. (See "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)".)


Zollinger-Ellison syndrome (ZES) is caused by secretion of gastrin by duodenal or pancreatic neuroendocrine tumors (gastrinomas). The annual incidence of gastrinomas is 0.5 to 2 per million population [3-5]. Most patients are diagnosed between the ages of 20 and 50, with a higher incidence in men as compared with women [6]. Approximately 80 percent of gastrinomas are sporadic, but 20 to 30 percent occur in association with multiple endocrine neoplasia type 1 (MEN1) [7]. (See "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)

Although gastrinomas are one of the most common functional pancreatic neuroendocrine tumors, only 25 percent of gastrinomas arise in the pancreas [6,8]. Approximately 50 to 88 percent of patients with sporadic ZES, and 70 to 100 percent of patients with ZES associated with MEN1, have duodenal gastrinomas. Duodenal gastrinomas are predominantly found in the first part of the duodenum. As compared with pancreatic gastrinomas, duodenal gastrinomas are usually small (<1 cm), are often multiple, and are less likely to have metastasized to the liver at diagnosis (0 to 10 versus 22 to 35 percent) [6,7,9,10]. In 5 to 15 percent of patients, gastrinomas arise in non-pancreatic, non-duodenal abdominal (stomach, peripancreatic lymph nodes, liver, bile duct, ovary), and extra-abdominal (heart, small cell lung cancer) locations [11,12].


The World Health Organization (WHO) classifies neuroendocrine tumors (NETs) arising within the digestive system into two broad categories, based upon the extent to which they resemble their normal nonneoplastic counterparts (table 1) (see "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on '2010 WHO classification') [13]:

Well-differentiated NETs, which are further classified, according to proliferative rate, into low-grade (G1) and intermediate-grade (G2) subgroups.

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Literature review current through: Nov 2017. | This topic last updated: May 16, 2017.
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