A 42-year-old woman with a history of recurrent peptic ulcer disease and chronic diarrhoea is found to have a fasting serum gastrin of 850 pg/mL (normal < 100). Gastric pH is 1.5. She has a past history of primary hyperparathyroidism treated surgically. Which investigation is most appropriate to confirm the suspected diagnosis and guide management?

Explanation

## Diagnosis: MEN 1 Syndrome with Gastrinoma This patient has the classic presentation of **MEN 1 (Wermer syndrome)** with: 1. **Primary hyperparathyroidism** (history of surgical treatment) 2. **Gastrinoma** (elevated fasting gastrin, peptic ulcer disease, diarrhoea) 3. **Gastric acid hypersecretion** (pH 1.5, refractory ulcers) ## Investigation of Choice: Secretin Stimulation Test + Imaging **Key Point:** The **secretin stimulation test** is the gold standard for confirming gastrinoma in patients with elevated fasting gastrin. A paradoxical rise in gastrin ≥ 200 pg/mL above baseline is diagnostic of gastrinoma. **High-Yield:** In MEN 1, gastrinomas are: - **Multiple** (70% of cases) - **Malignant** (60–90% are malignant) - **Occult** (70% are < 2 cm, difficult to localize) - Located in the **gastrinoma triangle** (junction of cystic and common bile ducts, junction of pancreatic neck and body) ### Why Secretin Stimulation Test? | Test | Mechanism | Diagnostic Threshold | Sensitivity | Specificity | | --- | --- | --- | --- | --- | | **Secretin stimulation** | Secretin paradoxically increases gastrin in gastrinoma | ≥ 200 pg/mL rise | 90% | 95% | | **Fasting gastrin alone** | Non-specific; elevated in many conditions | > 1000 pg/mL highly suggestive | 70% | 60% | | **Calcium stimulation** | Alternative confirmatory test (less used) | ≥ 400 pg/mL rise | 85% | 85% | | **Gastric pH** | Confirms acid hypersecretion | pH < 2 | 100% | Low specificity | **Clinical Pearl:** A fasting gastrin > 1000 pg/mL with gastric pH < 2 is virtually diagnostic of gastrinoma without need for secretin stimulation. However, this patient's gastrin (850 pg/mL) is in the borderline range, making secretin stimulation essential. ### Imaging After Confirmation **Mnemonic: "SOMATOSTATIN" imaging modalities for gastrinoma localization** - **S**omatostatin receptor scintigraphy (Octreoscan) — 70–90% sensitivity - **E**ndoscopic ultrasound (EUS) — 80–90% sensitivity for small tumours - **C**T/MRI abdomen — 60–70% sensitivity - **P**ositron emission tomography (PET) — emerging modality ## Diagnostic Algorithm for MEN 1 Gastrinoma ```mermaid flowchart TD A[Elevated fasting gastrin + Hyperparathyroidism]:::outcome --> B{Gastrin > 1000 pg/mL?}:::decision B -->|Yes| C[Likely gastrinoma]:::outcome B -->|No| D[Perform secretin stimulation test]:::action D --> E{Gastrin rise ≥ 200 pg/mL?}:::decision E -->|Yes| F[Confirm gastrinoma diagnosis]:::outcome E -->|No| G[Exclude gastrinoma]:::outcome F --> H[Localization imaging]:::action H --> I[EUS or Octreoscan]:::action I --> J[Surgical resection if localized]:::action J --> K[Long-term PPI therapy]:::action ``` **Management of MEN 1 Gastrinoma:** 1. **Confirm diagnosis** → Secretin stimulation 2. **Localize tumour** → EUS, Octreoscan, CT/MRI 3. **Assess for metastases** → Imaging of liver, regional lymph nodes 4. **Surgical resection** → If localized and resectable (curative intent) 5. **Medical management** → High-dose PPI (omeprazole 60–80 mg daily) for symptom control 6. **Screen for MEN 1 complications** → Pituitary adenoma, adrenal tumours, carcinoid syndrome [cite:Robbins 10e Ch 24; Harrison 21e Ch 438]