A 52-year-old man from Delhi presents with chronic epigastric pain and heartburn for 8 months. Upper endoscopy reveals multiple gastric ulcers with prominent gastric folds. Serum gastrin level is 850 pg/mL (normal <100). Which investigation is most appropriate to confirm the diagnosis of Zollinger-Ellison syndrome?

## Diagnosis of Zollinger-Ellison Syndrome **Key Point:** The secretin stimulation test is the gold standard confirmatory investigation for Zollinger-Ellison syndrome (ZES) when basal gastrin is elevated (>1000 pg/mL or 200–1000 pg/mL with clinical suspicion). ### Mechanism of Secretin Stimulation Test In ZES, gastrin-secreting tumours (gastrinomas) are paradoxically stimulated by secretin, unlike normal G-cells which are inhibited. The test protocol: 1. Obtain baseline fasting serum gastrin 2. Administer intravenous secretin (2 units/kg bolus) 3. Measure serum gastrin at 2, 5, 10, 15, and 30 minutes 4. **Positive result:** Gastrin rise ≥200 pg/mL above baseline confirms ZES ### Why Secretin Stimulation is Superior | Feature | Secretin Test | Fasting Gastrin | 24-hr Acid Output | CT Abdomen | |---------|---------------|-----------------|-------------------|------------| | **Diagnostic specificity** | 95–100% | Elevated but not diagnostic alone | Supports diagnosis but non-specific | Localizes tumour, not diagnostic | | **Confirms ZES** | Yes | No (only screening) | No | No | | **Differentiates from achlorhydria** | Yes (acid output measured) | No | Helps but indirect | No | | **Cost-effective** | Yes | Yes | No | No | **High-Yield:** In this patient, basal gastrin is 850 pg/mL (elevated but <1000). Secretin stimulation is indicated to confirm the paradoxical gastrin rise and establish ZES diagnosis with certainty. **Clinical Pearl:** Elevated fasting gastrin alone is NOT diagnostic—achlorhydria (atrophic gastritis, pernicious anaemia) also raises gastrin. Secretin stimulation distinguishes ZES (paradoxical rise) from achlorhydria (no rise or fall). ### Interpretation Algorithm ```mermaid flowchart TD A[Elevated fasting gastrin + PUD]:::outcome --> B{Gastrin level?}:::decision B -->|>1000 pg/mL| C[Secretin stimulation]:::action B -->|200-1000 pg/mL| D[Clinical suspicion high?]:::decision D -->|Yes| C D -->|No| E[Reassess diagnosis]:::outcome C --> F{Gastrin rise ≥200 pg/mL?}:::decision F -->|Yes| G[ZES confirmed]:::outcome F -->|No| H[ZES excluded]:::outcome I[Measure gastric pH & acid output] --> J{pH <2 & high acid?}:::decision J -->|Yes| K[Confirms gastrinoma]:::outcome J -->|No| L[Achlorhydria likely]:::outcome C -.-> I ``` [cite:Harrison 21e Ch 297]