Confirming the Diagnosis of Zollinger-Ellison Syndrome
The correct answer is C: Fasting serum gastrin is the most appropriate initial step to confirm the diagnosis of Zollinger-Ellison syndrome, with levels >1000 pg/mL combined with gastric pH <2 being diagnostic. 1, 2
Initial Diagnostic Approach
Fasting serum gastrin (FSG) measurement is the essential first diagnostic test for ZES. 1, 3 The American Gastroenterological Association recommends measuring FSG after discontinuing proton pump inhibitors for 1-2 weeks to avoid false elevations. 1
Interpretation of Fasting Serum Gastrin Levels:
- Gastrin levels >1000 pg/mL with gastric pH <2 are diagnostic for gastrinoma 2
- However, approximately two-thirds of gastrinoma patients have FSG values <10-fold normal, which overlap with more common conditions like H. pylori infection 3
- Normal FSG values are uncommon in ZES (0.3%-3% of cases) 3
- Very high FSG levels (>100-fold normal) occur in only 4.9%-9% of patients 3
Why Not the Other Options:
Calcium (Option A) is not used for ZES diagnosis. While calcium infusion was historically used as a provocative test, it has been replaced by the secretin stimulation test. 4
Vasoactive intestinal peptide (Option B) is used to diagnose VIPomas, not gastrinomas. VIPomas cause watery diarrhea-hypokalemia-achlorhydria syndrome, which is a different functional pancreatic neuroendocrine tumor. 5
When Additional Testing is Needed
For patients with mild hypergastrinemia (<10-fold normal), the secretin stimulation test is recommended to establish the diagnosis. 6, 4 This provocative test is necessary because FSG levels alone are not diagnostic in these cases, and gastrin provocative testing is required. 3
Critical Diagnostic Pitfall:
Renal failure is a common cause of hypergastrinemia that must be ruled out before pursuing ZES diagnosis. 1 Additionally, gastric acidity must be assessed through pH measurement or gastric analysis, as hypochlorhydria causes feedback stimulation of antral gastrin secretion, leading to elevated gastrin without ZES. 6
Clinical Context for Suspicion
ZES should be suspected in patients presenting with: 1, 6
- Severe peptic ulceration refractory to standard therapy
- Chronic diarrhea (occurs in approximately 50% at diagnosis)
- Gastroesophageal reflux disease refractory to standard therapy
- Multiple peptic ulcers or ulcers in unusual locations
- Epigastric pain lasting years despite acid-suppressive therapy (reported in 70% at diagnosis)
The average time between symptom onset and final diagnosis exceeds 5 years, emphasizing the importance of maintaining clinical suspicion. 2