Therapy with gastrin antibody in the Zollinger-Ellison syndrome

The therapeutic effectiveness of parenterally administered rabbit antigastrin antibody was evaluated in a patient with the Zollinger-Ellison syndrome who had a fasting serum gastrin level of 3020 pg/ml and a basal gastric acid secretion of 48.9 mEq/hr. Control globulin reduced gastric secretion to 32 mEq/hr. Gastrin antibody reduced it further to 8.7 mEq/hr. Betazole hydrochloride which was given 75 min after administration of gastrin antibody stimulated acid secretion to 57.2 mEq/hr. One day later basal acid secretion was uninhibited although some antibody activity was present in the patient's serum. The results suggested that gastrin antibody acutely inhibited basal but not betazole-stimulated secretion.A portion of this paper was presented to the Gastroenterology session of the American Federation for Clinical Research, Southern Section, January 25, 1973.     

Variability of serum gastrin levels in Zollinger-Ellison syndrome

A patient with recurrent peptic ulceration and presumed Zollinger-Ellison syndrome whose serum gastrin concentration varied widely is reported. Two antisera, one directed predominantly against nonsulfated gastrin and the other measuring both sulfated and nonsulfated gastrin, showed that in addition to wide variation in gastrin levels, this patient secreted his gastrin predominantly in the sulfated G34 form. The possibility of variable serum gastrin levels, which may reflect either spontaneous variation in gastrin output from Z-E tumors or differing specificity of the antiserum utilized in the immunoassay, may be of importance in the diagnosis and management of patients with the Zollinger-Ellison syndrome. Because of gastrin heterogeneity in the Z-E syndrome, this study reinforces the concept that a broad spectrum antibody, detecting all gastrin components should be routinely used in detection of patients suspected of having the Z-E syndrome.This work was supported by grants from the National Health and Medical Research Council and the Australian Tobacco Research Foundation.     

Repeated vomiting of gastric juice in a patient with Zollinger-Ellison syndrome

Digestive Diseases and Sciences -     

Pseudo Zollinger-Ellison syndrome in a patient with duodenal stenosis caused by tuberculosis

We report the case of a 32-year-old Indian man with symptoms suggesting Zollinger-Ellison syndrome including abdominal pain, esaphagitis, duodenal stenosis that did not improve with antisecretory medication, elevated fasting gastrin serum levels that increased after intravenous secretin injections, elevated chromogranin A serum levels and tumoral aspect of pancreatic uncus on CT scan examination. A pancreaticoduodenectomy was performed. Histological examination of the resected specimen showed that there was no endocrine tumour of the pancreas or the duodenum, but identified marked lesions of follicular and caseous tuberculosis. The final diagnosis retained pseudo Zollinger-Ellison syndrome due to gastric outlet obstruction caused by duodenal stenosis of a tuberculosis origin.     

Mechanism for increase of gastrin release by secretin in Zollinger-Ellison syndrome

In patients with Zollinger-Ellison syndrome, serum gastrin level is increased by secretin and is decreased by somatostatin. To elucidate the cellular mechanism for these actions, we investigated the direct effects of secretin and somatostatin on dispersed gastrinoma cells from a patient with Zollinger-Ellison syndrome. In the presence of 3-isobutyl-1-methylxanthine, secretin significantly stimulated gastrin release from dispersed gastrinoma cells, which was inhibited by somatostatin. In the presence of guanosine 5'-triphosphate, furthermore, secretin enhanced adenylate cyclase activation in the membranes from these cells, and this activation was reduced by somatostatin, whereas neither secretin nor somatostatin affected inositol phospholipid turnover. On the other hand, removal of guanosine 5'-triphosphate from incubation medium abolished both the stimulatory effect of secretin and the inhibitory effect of somatostatin on adenylate cyclase activation. Furthermore, pertussis toxin pretreatment reversed the ability of somatostatin to inhibit secretin-induced increase in gastrin release and activation of adenylate cyclase. Thus, in this gastrinoma patient, secretin and somatostatin appeared to act directly on gastrinoma cells to stimulate and inhibit gastrin secretion, respectively, by modulating adenylate cyclase activation, probably via guanine nucleotide-binding proteins.     

Development of sustained achlorhydria in a patient with the Zollinger-Ellison syndrome treated with omeprazole.

Spontaneous remission of gastric acid hypersecretion in the Zollinger-Ellison syndrome occurs rarely. This study shows the development of gastric secretory mucosal atrophy resulting in achlorhydria and loss of pepsin secretion in a 63-year-old woman with the Zollinger-Ellison syndrome. Reduced secretion began soon after starting treatment with omeprazole, and achlorhydria became complete 6 months later. The patient remains well with normal endoscopy results and is achlorhydric 4 years after the start of treatment and 34 months after stopping omeprazole. She was not colonized with Helicobacter pylori until 36 months after developing achlorhydria. Serum gastrin has increased from 1000 to between 5000 and 12,500 ng/L (pg/mL), was not suppressible by gastric acidification, and was not associated with G-cell hyperplasia. She also has a normal Schilling test and normal immunoglobulins, and lacks antibodies to parietal cells or H+, K(+)-ATPase. Moderate enterochromaffinlike cell hyperplasia is apparent for the first time on the latest biopsy sample.     

Postoperative bleeding in a patient with normal screening coagulation tests

A 54-year-old man was brought to the emergency room after a head-on collision. He had multiple fractures in his lower extremities and required immediate surgery. After surgery, the patient had a persistent drop in hemoglobin, hematocrit and platelets despite red blood cell transfusions. Laboratory studies included normal prothrombin time, activated partial thromboplastin time, normal plasminogen functional activity, negative antiplatelet antibodies, normal platelet functional analysis and negative disseminated intravascular coagulation screen. Factor XIII antigen levels were 25% of predicted, and the diagnosis of factor XIII deficiency was made. The patient was treated with cryoprecipitate, and the bleeding stopped. Patients with factor XIII deficiency have either a rare congenital or acquired coagulation disorder. Both presentations have normal standard laboratory clotting tests, and the diagnosis requires an assay measuring factor XIII activity or antigen levels. The usual treatment includes cryoprecipitate, fresh-frozen plasma or recombinant factor XIII. This deficiency should be considered in patients with unexplained spontaneous, traumatic or postoperative bleeding.     

Clinical recovery owing to target parietal cell failure in a patient with Zollinger-Ellison syndrome.

A patient is presented with Zollinger-Ellison syndrome, in whom spontaneous disappearance of gastric hypersecretion and peptic ulcer disease occurred subsequent to an intercurrent illness causing acute nonspecific inflammation of the gastric mucosal lining. The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged.     

Zollinger-Ellison syndrome with pneumopericardium

Summary A 55-year-old white male was found to have the Zollinger-Ellison syndrome in 1971. Supposed total gastrectomy was performed at that time. When an esophageal ulcer was found, six years later, esophagoscopic biopsy revealed residual gastric mucosa. The patient was given cimetidine 300 mg qid because it was felt he could not tolerate further surgery. After eight months of cimetidine therapy, the patient was admitted to the hospital because of retrosternal pain. Pneumopericardium was discovered, and at autopsy a large penetrating gastrojejunal ulcer was demonstrated.Supported by the Medical Research Service of the Veterans Administration.     

Gastrin cell distribution in normal human stomachs and in patients with Zollinger-Ellison syndrome.

Quantitative distribution of gastrin cells was evaluated in three normal human stomachs and in four stomachs from patients with Zollinger-Ellison syndrome. Cells identified by the immunoperoxidase method were counted along the entire length of five mucosal strips parallel to the axis of the lesser curvature and sampled from the posterior to the anterior walls. The number of cells per unit area (2300 microns2) decreased from the pylorus to the borderline of the gastric body from (mean +/- SEM) 50.9 +/- 12.0 to 24.2 +/- 13.0 and from 29.6 +/- 5.6 to 10.4 +/- 2.6 for control and Zollinger-Ellison syndrome, respectively, with large interindividual variations. From factorial analysis no statistical difference was found between the two groups. It is therefore suggested that the number of gastrin cell in antral mucosa may not be a significant criteria in the diagnosis of Zollinger-Ellison syndrome.