Brief History and Evolution of the Zollinger Ellison Syndrome

The history behind the identification and characterization of the Z-E syndrome is fascinating. Four decades of investigating the pathophysiology and natural history, searching for drugs to inhibit the marked gastric acid hypersecretion, developing new technologies to diagnose and locate the tumors, and searching for the preferred treatment for patients with Z-E syndrome have captivated many physician-scientists, some of whom could appropriately be dubbed "Z-E watchers." Some Z-E watchers have made the study of this disease entity a focus of their research and clinical practice. Their contributions have altered our approach to the diagnosis, management, and treatment of this disease.1,7 28

In 1955, at the annual meeting of the American Surgical Association, Robert M. Zollinger and Edwin H. Ellison reported the clinical histories of two patients with primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. They suggested a diagnostic triad for a new clinical syndrome1:

1. The presence of primary ulcerations in unusual locations, that is, second or third portions of the duodenum or upper jejunum, or recurrent stomal ulcers after any type of gastric surgery short of total gastrectomy (TG)

2. Gastric hypersecretion of gigantic proportions persisting despite adequate conventional medical, surgical, or irradiation therapy

3. The identification of nonspecific islet cell tumors of the pancreas (an "ulcerogenic tumor factor of pancreatic islet origin" was postulated)

The subsequent reports detailing the early descriptions of patients with ulcerogenic tumors, the discovery of a potent gastric secretagogue in the tumor tissue and the sera of Z-E syndrome patients, the identification of gastrin as the responsible hormone, and the development of radioimmunoassay (RIA) methods to measure physiologic and supranormal gastrin concentrations all make fascinating reading. This history has been recorded by Zollinger and Coleman.29

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