THE ZOLLINGER-ELLISON SYNDROME



The Zollinger-Ellison syndrome, usually caused by a functioning islet cell tumor that secretes gastrin, accounts for well under 1 per cent of clinically diagnosed peptic ulcers. The possi­bility of this rare entity should be considered in several circumstances: (1) ulcers in unusual lo­cations such as the second or third portions of the duodenum or the jejunum, (2) unusually severe peptic ulcer disease that is refractory to treatment or that is recurrent after surgery, (3) ulcer disease accompanied by diarrhea and sometimes malab­sorption (see Chapter 36], and (4) a strong family history of ulcer disease, especially if there is ev­idence of other endocrine tumors.

Pathogenesis. Single or often multiple gastri­nomas in the pancreas, or more rarely in other abdominal but extrapancreatic sites, secrete ex­cessive amounts of gastrin. This hormone drives acid secretion by the parietal cells as well as hav­ing a trophic effect in increasing their number (as much as three to five times). Although these tu­mors are slow-growing, most are histologically and biologically malignant with early metastases regionally and to the liver. In approximately one fourth of patients the gastrinoma is associated with other endocrine adenomas, most commonly in the pattern known as the multiple endocrine neoplasia Type II syndrome (MEN II] in which adenomas or hyperplasia may involve the islet cells, the parathyroid glands, the thyroid, and the pituitary.

Clinical Manifestations. The clinical manifes­tations are usually those of severe peptic ulcer dis­ease as noted above. Rarely diarrhea may precede peptic ulcer formation or be a more prominent part of the symptomatology.

Diagnosis. The diagnosis of the Zollinger-El-lison syndrome is not usually difficult if it is con­sidered. In general it depends on the demonstra­tion of an elevation of serum gastrin in the presence of increased basal secretion of gastric acid. The diagnosis may require use of a stimu­lation test with pentagastrin to show that basal acid secretion is greater than 40 per cent of that under maximal stimulation.

Treatment. An attempt should be made to find and remove a resectable tumor, although this can be done in only about one quarter of patients. If not successful, patients should be treated with full doses of an H2-receptor antagonist such as cime-tidine or ranitidine.