Zollinger-Ellison Syndrome

Excerpt

Zollinger-Ellison syndrome (ZES) is a group of symptoms comprised of severe peptic ulcer disease, gastroesophageal reflux disease (GERD), and chronic diarrhea caused by a gastrin-secreting tumor of the duodenum or pancreas (gastrinoma triangle) that results in increased stimulation of acid-secreting cells of the stomach. Gastrinoma is a functional neuroendocrine tumor that secretes gastric acid, which causes ZES. The earlier misconception was that the location of gastrinoma was in the pancreas. However, gastrinomas occur in the duodenum more than the pancreas by three times, especially in the first portion of the duodenum. There are other non-neuroendocrine tumors secreting gastrin, but not at a level to cause significant symptoms.

Gastrinoma-causing Zollinger-Ellison syndrome occurs sporadically in about 80% of cases and is reported to be 20% to 25% as multiple endocrine neoplasia type 1 (MEN1) from multiple reports in the literature. Approximately 50% of patients with MEN1 have ZES; therefore, MEN1 must be included in a workup if the clinician suspects ZES. It takes an average of 8 years from the start of symptoms to diagnosis due to the widespread use of proton pump inhibitors (PPIs). One study of two referral centers, one in Italy and one in the United States, showed a 62% decrease in referrals and diagnosis of ZES compared to when PPIs were used less frequently.

Zollinger-Ellison syndrome first appeared in the Annals of Surgery in 1955 as a case series compiled by two surgeons from Ohio State University, Dr. Robert M. Zollinger and Edwin H. Ellison. Both cases had ulcers at the upper jejunum with excess gastric acid production refractory to medical and surgical therapy, including gastrectomy. The ultimate finding that led to ZES with hypersecretion, hyperacidity, and recurrent peptic ulceration was a non-beta cell islet tumor of the pancreas. The pioneer case series induced enough interest to publish multiple studies that recognize the connections between gastrinoma and ZES.