Serum Gastrin in Zollinger-Ellison Syndrome

Abstract

The assessment of fasting serum gastrin (FSG) is essential for the diagnosis and management of patients with the Zollinger-Ellison syndrome (ZES). Although many studies have analyzed FSG levels in patients with gastrinoma, limited information has resulted from these studies because of their small size, different methodologies, and lack of correlations of FSG levels with clinical, laboratory, or tumor features in ZES patients. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of 309 patients with ZES and compare our results with those of 2229 ZES patients in 513 small series and case reports in the literature. In the NIH and literature ZES patients, normal FSG values were uncommon (0.3%-3%), as were very high FSG levels >100-fold normal (4.9%-9%). Two-thirds of gastrinoma patients had FSG values <10-fold normal that overlap with gastrin levels seen in more common conditions, like Helicobacter pylori infection or antral G-cell hyperplasia/hyperfunction. In these patients, FSG levels are not diagnostic of ZES, and gastrin provocative tests are needed to establish the diagnosis. Most clinical variables (multiple endocrine neoplasia type 1 status, presence or absence of the most common symptoms, prior medical treatment) are not correlated with FSG levels, while a good correlation of FSG values was found with other clinical features (prior gastric surgery, diarrhea, duration from onset to diagnosis). Increasing basal acid output, but not maximal acid output correlated closely with increasing FSG. Numerous tumoral features correlated with the magnitude of FSG in our study, including tumor location (pancreatic > duodenal), primary size (larger > smaller) and extent (liver metastases > local disease). In conclusion, this detailed analysis of FSG in a large number of patients with ZES allowed us to identify important clinical guidelines that should contribute to improved diagnosis and management of patients with ZES.

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers

“…In addition, the use of chronic proton pump inhibitors (PPIs) leads to high FSG levels and therefore gastrin provocative tests are needed to establish the diagnosis of ZES. Indeed, in a recent prospective analysis, up to two-thirds of gastrinoma patients were found to have FSG values <10-fold normal [27]. The gold standard is the secretin test [27,28,29,30,31].…”

Diagnostic Efficacy of the Secretin Stimulation Test for the Zollinger-Ellison Syndrome: An Intra-Individual Comparison Using Different Dosages in Patients and Controls

“…We performed a unique study by comparing low and high dose secretin within patients, a study that has never been done before. In addition, other than the study by the NIH in the US of 293 patients from 1974 to 2005 [4], no larger study has ever been reported before. In the literature only 42 patients have received 0.78 µg/kg secretin as compiled from 12 studies [4], making our study, containing 25 patients and 57 secretin tests, a large study in comparison with those other studies.…”

“…In most previous publications, serum gastrin responses to secretin of >200 ng/l, introduced by McGuigan and Wolfe [10], were used as the criterion for a positive test. Recently, Berna et al [4,5] studied the secretin stimulation test in 293 patients and compared with 537 patients from the literature, and recommended to use a gastrin increase of 120 ng/l. We investigated the most optimal criterion with emphasis for a positive test to diagnose ZES and found a post-secretin gastrin elevation of >100 ng/l to be the most optimal discriminating value between ZES and non-ZES patients, which was also confirmed in a validation group.…”

“…100–1,000 ng/l, determinations of FSG levels alone will not be diagnostically conclusive and additional methods are needed. The secretin stimulation test is the diagnostic tool of choice in subjects with FSG levels <1,000 ng/l [4,5]. As several criteria for a positive test have been reported in the literature, we investigated which criterion for a positive test resulted in the highest sensitivity and specificity in our patients.…”

Radionuclide imaging and therapy in patients with neuroendocrine tumors

“…Высокий уровень ХГ-А чаще наблю-дается при НЭО средних отделов (midgut) ЖКТ, особенно при метастазах в печень, а также при нефункционирующих опухолях поджелудочной железы [44,45]. Следует от-метить, что повышение ХГ-А отмечается у пациентов, получающих терапию ингибито-рами протонной помпы, страдающих хрони-ческим атрофическим гастритом, почечной недостаточностью, застойной сердечной не-достаточностью и циррозом печени.…”