Impact of Stress on Serum Gastrin in Zollinger-Ellison Syndrome

We report an impressive case with Zollinger-Ellison syndrome (ZES), in which stress-induced sympathetic discharge influenced serum gastrin. Our patient was a 35-yr-old female who complained of frequent and massive vomiting (more than 4000 ml of gastric juice) which was aggravated especially by psychosocial stress. Basal hypergastrinemia (1900 pg/ml) was found after the admission. The most striking finding was that laboratory stress dramatically increased serum gastrin (from 1900 to 5400 pg/ml) and plasma noradrenaline (from 180 to 1130 pg/ml). Mental arithmetic stress further enhanced hypergastrinemia (5800 pg/ml) with a concomitant increase in plasma noradrenaline (1240 pg/ ml). Neostigmine (10 μg/kg im) also increased serum gastrin up to 6100 pg/ml but propranolol (40 μg/kg iv) reduced these elevations (noradrenaline: 990 pg/ml, gastrin: 5000 pg/ml). In this case, the effect of stress on serum gastrin mimicked the effect of catecholamine infusion in ZES. These findings suggest that psychological stress induces serum gastrin secretion via β-adrenoceptor with exacerbation of symptoms in some cases with ZES.     

Bioassay and Radioimmunoassay of Plasma Gastrin in a Case of Zollinger-Ellison Syndrome

Fasting plasma gastrin levels were measured in a patient with the Zollinger-Ellison syndrome by both bioassay and radioimmunoassay. The level remained constant following total gastrectomy, but fell sharply following parathyroidectomy. Although the bioassay gave gastrin levels which were consistently 2 to 3 times higher than those obtained by radioimmunoassay, the values showed a similar trend. However, both methods gave almost identical results for the gastrin contents of antral mucosa and pancreatic tumour samples from the patient. It is suggested that biologically active gastrin-like substances not detectable by radioimmunoassay were present in the patient's plasma.     

血清胃蛋白酶原与胃泌素检测对慢性萎缩性胃炎的诊断价值

目的探讨血清胃蛋白酶原Ⅰ（PGⅠ）、胃蛋白酶原Ⅰ/胃蛋白酶原Ⅱ（PGⅠ/PGⅡ）比值（PGR）和胃泌素-17（G-17）与慢性萎缩性胃炎的关系,确定其在萎缩性胃炎中的变化规律。方法 选择在我院消化科行胃镜检查符合入选研究标准的300例患者,根据组织病理学诊断结果分为慢性非萎缩性胃炎组（202例）和慢性萎缩性胃炎组（98例）。采用酶联免疫吸附试验（ELISA）方法定量测定空腹血清PGⅠ、PGⅡ和G-17水平,并计算PGⅠ/PGⅡ比值（PGR）。采用14C-或13C-呼气试验和快速尿素酶试验两种方法联合判定幽门螺杆菌（Hp）感染情况。结果 慢性萎缩性胃炎组与非萎缩性胃炎组相比,血清PGⅠ分别为128.55±61.42μg/L和150.61±75.33μg/L,比较有显著差异（P〈0.05）。PGR分别为10.09±5.15和10.95±7.18,比较无显著差异（P〉0.05）;G-17分别为9.68±15.51pmol/L和18.93±18.92pmol/L,比较有显著差异（P〈0.05）。Hp阳性组PGR（8.96±7.72）与阴性组（11.63±5.56）比较有显著差异（P〈0.05）;Hp阳性组PGⅠ（125.39±65.90μg/L）与阴性组（154.19±65.13μg/L）比较有显著差异（P〈0.05）;Hp阳性组G-17（10.91±15.50pmol/L）与阴性组（10.68±19.12pmol/L）比较无显著差异（P〉0.05）。结论 联合检测血清PG和G-17水平可用于慢性萎缩性胃炎的筛查,如有异常,应进一步行胃镜检查以确诊并指导治疗。Hp感染与PG水平的变化有关。     

Testing for Helicobacter pylori in the Diagnosis of Zollinger-Ellison Syndrome

Infection with Helicobacter pylori is associated with almost all cases of peptic ulcer. Using Bayes' formula, we evaluated whether testing for H. pylori in a patient with proven ulcer might help in the work-up of a Zollinger-Ellison syndrome (ZE). A negative test for H. pylori in a patient with duodenal ulcer would raise a pretest probability for ZE of 10-20% to a posttest range of 61-78%. The information provided by a negative test result with respect to ZE is greater in younger than in older ulcer patients. It is also greater in duodenal than gastric ulcer. We conclude that testing for H. pylori in ulcer patients, in whom ZE constitutes a possible differential diagnosis, adds substantially to the decision making at relatively low cost and little additional risk to the patient.     

Secretin-Induced Gastrin Response in the Zollinger-Ellison Syndrome and Chronic Duodenal Ulcer Patients before and after Cimetidine Treatment

A secretin provocative test was performed in 16 patients with chronic duodenal ulcer and in five patients with the Zollinger-Ellison syndrome. In four chronic duodenal ulcer patients a second secretin test was done during acute iv cimetidine administration. There were only slight variations of gastrin compared with the first test. A third test was done on the same four chronic duodenal ulcer patients after 1 month's po cimetidine treatment (1 g/day); gastrin at 0 time was significantly higher than in the previous two tests (p < 0.01). Integrated gastrin response after secretin was significantly lower in the third test than in the first (p < 0.05). In two Zollinger-Ellison syndrome patients treated with 1.0 and 1.4 g/day cimetidine for 3 months, gastrin at 0 time was not markedly increased, whereas compared with the first test gastrin levels were higher at each time after secretin. These data suggest that previous cimetidine treatment does not alter, and may even increase, the diagnostic sensitivity of the secretin test.     

Antral Gastrin Cells and Serum Gastrin in Achlorhydria

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy specimens from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis, the mean number of gastrin cells per field of vision was 52±6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin level was 324±56 pmol/1 and the number of gastrin cells was 79.6±7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361±186 pmol/1 and 88.0±14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0±3.3 pmol/1, and the number of gastrin cells was 6.2±3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.     

Is Pancreatic Polypeptide Estimation of Value in Diagnosing Gastrinomas (Zollinger-Ellison Syndrome)?

Summary: Is pancreatic polypeptide estimation of value in diagnosing gastrinomas (Zollinger-Ellison syndrome)? D. J. Byrnes, J. Marjason, L. Henderson, N. Gallagher and D. Fabricatorian, Aust. N.Z. J. Med., 1979, 9, pp. 364–366. Serum levels of pancreatic polypeptide (PP) were determined in 32 normal subjects, 18 patients with gastrinoma, 19 patients with pituitary adenoma and 11 patients with duodenal ulceration. Mean serum levels of PP in patients with gastrinomas (67±31 pmol/ (SD)) were significantly (P < 0·01) higher than in the normal subjects (47 ± 15 pmol/). However, only five of 18 of the patients with gastrinomas had PP levels above the upper limit of normal and elevations of similar magnitude were observed in patients with other disease processes. It is therefore concluded that serum PP estimations are not of value in the diagnosis of gastrinomas.     

Serum Gastrin in Chronic Pancreatitis

Fasting serum gastrin and gastrin response to a protein meal were measured in a group of patients with chronic pancreatitis and in controls. No significant differences were found between the two groups of subjects. In patients with chronic pancreatitis no relation was found between gastrin release and the severity of pancreatic exocrine insufficiency.     

幽门螺杆菌相关性慢性胃炎中医辨证分型与胃泌素的关系

目的:研究幽门螺杆菌(Hp)相关性慢性胃炎中医辨证分型与空腹血清胃泌素(GAS)的关系.方法:将中医辨证为脾胃湿热型、脾胃虚弱型的42例慢性胃炎患者进行电子胃镜、病理组织学检查,并检测Hp及血清GAS.结果:Hp相关性慢性胃炎中脾胃湿热型占62.96%(P<0.05);空腹血清GAS(125.35 ng/L)高于脾胃虚弱型(96.59 ng/L,P<0.01).结论:高GAS血症可能是Hp相关性慢性胃炎脾胃湿热证型重要病理生理基础之一.     

Zollinger-Ellison Syndrome Unresponsive to Cimetidine

A patient with Zollinger-Ellison syndrome appeared initially to respond to cimetidine with a reduction in gastric acid secretion. Symptoms immediately improved but after three days recurred with increasing severity. Intravenous cimetidine had only a short-lived and partial inhibitory effect on the rate of acid production and because of continuing pain and progressive bleeding from his duodenal ulcer, total gastrectomy was performed. Evidence of the effect of atropine and of oral and intravenous cimetidine is presented. Despite recent optimism, cimetidine is not always adequate treatment for Zollinger-Ellison syndrome.     

Association of Zollinger-Ellison Syndrome with Pancreatitis

In a retrospective analysis, five cases of Zollinger-Ellison syndrome were found in a typical urban inner-city teaching hospital. Chronic alcohol abuse and heavy smoking characterized these patients, and four of them also had pancreatitis, suggesting an association of gastrin-producing tumors and pancreatic inflammation. Ductal obstruction by neuroendocrine tumors has been reported to cause pancreatitis in a few cases. In this analysis, however, a nonobstructive gastrinoma was the surgical diagnosis in three patients, and it was suggested by imaging studies in the two other cases. The potential other pathomechanisms for a dual cause–effect relationship of gastrinoma and pancreatitis are discussed.     

Biologic and Immunologic Gastrin Activity in Serum of Patients with Gastrinoma. Bioassay of Gastrin Activity in Serum

The biologic gastrin activity in serum from 14 patients with the Zollinger-Ellison syndrome was assessed by the stimulation of histamine release and acid secretion from the isolated vascularly perfused rat stomach and compared with the immunologic activity as determined by radioimmunoassay using an antibody directed towards the active site of the gastrin molecule. Biologic gastrin activity assessed by the stimulation of histamine release was more closely correlated to immunologic gastrin activity than biologic activity assessed by the stimulation of gastrin acid secretion. This study does not contradict the concept that gastrin stimulates acid secretion at least partly by releasing histamine and also shows that the immunologic gastrin activity determined with the help of an antibody directed towards the active site reflects biologic activity.     

Serum Gastrin and Gastric Acidity

Summary: The relationship between serum levels of gastrin and intragastric acidity was studied using an immunoassay for gastrin which was specific for the biologically active C-terminal sequence of the gastrin molecules.
Eighty-three combined serum gastrin and intragastric pH estimations were performed on 43 subjects (4 normal, 13 patients with gastric ulceration and 26 patients with duodenal ulceration). The serum gastrin response to gastric acidification by betazole hydrochloride was studied in 9 patients with duodenal ulceration.
There was a highly significant (P <0.001) negative correlation (r=-0.37) of serum gastrin on basal intragastric pH, i.e. the patients with the higher gastrin levels had lower intragastric pH. Gastric acidification by betazole hydrochloride suppressed the hyper-gastrinaemia associated with duodenal ulceration.
The correlation between serum gastrin and intragastric pH suggests that gastrin is a factor in maintaining basal gastric acid secretion. Suppression of the hypergastri-naemia associated with duodenal ulceration by gastric acidification is consistent with the concept of an increased vagal tone in these patients.     

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.     

Diagnosis and treatment of Zollinger-Ellison syndrome

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.     

Diagnosis and management of Zollinger-Ellison syndrome

With the recent widespread availability of gastrin radioimmunoassays, the development of increasingly effective medical therapy for gastric hypersecretion, and improved methods to localize gastrinomas in patients with Zollinger-Ellison syndrome, the diagnosis, treatment of the gastric acid hypersecretion, and approach to the tumor have changed significantly. Recent advances in each of these areas and the current management of a patient with Zollinger-Ellison syndrome are reviewed.     

Zollinger-Ellison Syndrome with Esophagitis and Barrett Mucosa

Although esophageal disease in Zollinger-Ellison syndrome is being recognized with increasing frequency, Barrett esophagus is seen only rarely. Basal lower esophageal sphincter pressure is probably not different in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome patients. Circulating gastrin, therefore, cannot be the major determinant of lower esophageal sphincter pressure in vivo . Total gastrectomy and resection of all metaplastic esophagus, when feasible, is the treatment of choice for patients with Zollinger-Ellison syndrome and Barrett mucosa.