Review Article: Strategies to Determine Whether Hypergastrinaemia Is Due to Zollinger-Ellison Syndrome Rather Than a More Common Benign Cause

S.V.M. Murugesan; A. Varro; D.M. Pritchard


Aliment Pharmacol Ther. 2009;29(10):1055-1068. 

In This Article

Other Potential Investigations

Acid Output Studies

Gastric juice pH testing is essential for the diagnosis of ZES. This can be achieved simply by aspiration of gastric juice at endoscopy or via a nasogastric tube. Hypergastrinaemia with a gastric pH > 2 is almost never due to ZES, unless patients are taking acid suppressing drugs.[4,6,26,89] Several authors have additionally investigated the role of acid output studies in the diagnosis of ZES. Basal acid output (BAO) is usually measured after an overnight fast because there is normally a circadian rhythm of acid output with the lowest concentration pre-breakfast (in the morning) and the highest concentration in the evening. MAO (maximal acid output or maximal secretory capacity of the stomach) is determined by the measurement of gastric output for 90 min following pentagastrin administration.[90] Previous studies have shown that in ZES the BAO is increased to over 15 mEq/h in the absence of previous acid reducing surgery and is increased to over 5 mEq/h in those patients with ZES who have had previous acid reducing surgery.[6,91,92,93] When the ratio of BAO/MAO exceeds 0.6, the diagnosis of ZES is thought to be likely.[6,94] This is due to the blunting of the secretory response of the stomach due to the pre-existing high basal acid output state secondary to the hypergastrinaemia seen in ZES. However, in recent years with the withdrawal of pentagastrin, MAO studies can no longer be routinely performed.

There may therefore still be a clinical role for acid output studies in patients with an equivocal provocation test and hypergastrinaemia.[95] Acid output studies also remain useful in the evaluation of the effectiveness of antisecretory agents, as there is a well documented lack of correlation between symptoms and acid output status in patients being treated with these drugs.[96]

Venous Sampling and Arterial Stimulation Venous Sampling

Venous sampling with or without arterial stimulation has a limited role for investigating the cause of hypergastrinaemia. However, such investigations may be useful for the localization of gastrinomas which have been confirmed by other investigations such as provocation tests. As mentioned above, in view of the small size or multicentric nature of many gastrinomas, particularly those associated with MEN type-1, tumour localization may be difficult with the use of standard imaging modalities such as CT, EUS and somatostatin receptor scintigraphy (SRS, octreotide scan). Conventional CT scanning identifies a primary gastrinoma in about 40% of patients subjected to surgery[97] and additional angiography identifies a further 20% of primary tumours.[98] SRS localizes primary gastrinomas in 60-70% of patients and the routine use of SRS has been shown to change management in 15-45% of patients.[99]

Arterial stimulation and venous sampling (ASVS) can provide both anatomical and functional information about gastrinomas. Initially, secretin was used for stimulation of gastrin secretion, but calcium gluconate has also been shown to be equally effective.[100] Imamura et al. describe a case series of the use of SASI (selective arterial secretin injection) in locating gastrinomas not visualized by conventional imaging modalities. In all three patients described, the SASI technique helped to localize tumours.[101] In a subsequent series, the same authors describe a 100% positive predictability rate as well as a 100% negative predictability rate for the SASI test for preoperative localization of functioning gastrinomas.[102] In independent series, Dopmann et al. describe a 77% diagnostic rate by combining angiography with intra-arterial secretin injection compared to a 38% diagnostic rate with angiography alone, while Rosato et al. report similar results.[103] Turner et al. found that calcium infusion had a higher specificity and sensitivity than the secretin infusion test[100] and this has been confirmed in a subsequent series, even when patients remained on acid suppressing medication.[104] Although most results have been obtained from case series, visceral angiography combined with arterial stimulation and venous sampling is probably a highly sensitive technique for the localization of gastrinomas and may therefore be useful for the pre-operative assessment of selected patients. Complications associated with this procedure include abdominal pain, haemobilia, superior mesenteric vein occlusion and arteriovenous fistulae. Although some authors feel that ASVS has not proven useful, the recent ENETS guidelines do suggest a role for ASVS following secretin infusion in cases where conventional imaging including EUS (endoscopic ultrasound) has proven negative.[59]