What is the next diagnostic test for a patient with refractory peptic ulcer disease and chronic diarrhea?

Diagnostic Approach for Refractory Peptic Ulcer Disease with Chronic Diarrhea

Serum gastrin level testing should be performed next in this patient with refractory peptic ulcer disease and chronic diarrhea to evaluate for gastrinoma (Zollinger-Ellison syndrome).

Clinical Presentation Analysis

This 54-year-old man presents with a highly suspicious constellation of symptoms:

• Abdominal pain and watery diarrhea for 2 years
• Endoscopy-confirmed peptic ulcer disease with multiple ulcers
• Refractory to proton pump inhibitor therapy
• Epigastric tenderness on examination

These findings strongly suggest Zollinger-Ellison syndrome (ZES), which is characterized by:

• Gastrin-secreting neuroendocrine tumors (gastrinomas)
• Gastric acid hypersecretion
• Multiple, refractory peptic ulcers
• Chronic diarrhea

Diagnostic Algorithm

Step 1: Serum Gastrin Level Testing

• Measure fasting serum gastrin level as the initial diagnostic test
• Gastrin levels >100 pg/mL are suspicious; levels >1000 pg/mL with gastric pH <2 are diagnostic for gastrinoma 1
• Patient should discontinue PPIs for at least one week and H2 blockers for 48 hours before testing 1

Step 2: If Gastrin Elevated, Confirm with Secretin Stimulation Test

• Secretin stimulation test helps differentiate ZES from other causes of hypergastrinemia
• A rise in serum gastrin of >120 pg/mL after secretin administration is diagnostic for gastrinoma 1

Step 3: Localization Studies (if ZES confirmed)

• Endoscopic ultrasound (sensitivity up to 83% for pancreatic gastrinomas) 1
• Somatostatin receptor scintigraphy (SRS) or Gallium-68 DOTATOC PET (highest sensitivity) 2, 1
• CT scan with contrast for additional imaging 3

Rationale for Serum Gastrin Testing

1. Classic Presentation: The combination of refractory multiple peptic ulcers and chronic diarrhea is highly suggestive of ZES 4

2. Refractory to PPI Therapy: Patients with ZES typically require higher doses of PPIs to control symptoms due to excessive acid production 5

3. Chronic Nature: The 2-year history of symptoms is consistent with the often delayed diagnosis of ZES (average delay >5 years) 4

4. Age and Presentation: Middle-aged patients with refractory peptic ulcer disease should raise suspicion for gastrinoma 2

Alternative Diagnostic Considerations

While serum gastrin testing is the most appropriate next step, other conditions to consider include:

1. Bile Acid Diarrhea

   • Can present with chronic watery diarrhea
   • Testing options include SeHCAT testing or serum 7α-hydroxy-4-cholesten-3-one 6
   • However, this wouldn't explain the refractory peptic ulcers

2. Microscopic Colitis

   • Can cause chronic watery diarrhea
   • Diagnosed by colonoscopy with biopsies 6
   • Wouldn't explain the refractory peptic ulcers

3. Celiac Disease

   • Can present with chronic diarrhea
   • Test with IgA-tTG and a second test to detect celiac disease in IgA deficiency 6
   • Wouldn't explain the refractory peptic ulcers

Management Implications

Early diagnosis of ZES is critical because:

• Gastrinomas have a high rate of malignancy 1
• Appropriate treatment requires higher doses of PPIs (often 2-3 times standard doses) 5
• Surgical resection may be curative in up to 30% of cases without metastasis 2

Common Pitfalls to Avoid

1. Premature diagnosis of functional disorders without excluding ZES in patients with refractory PUD and diarrhea 7

2. Inadequate PPI withdrawal before serum gastrin testing, leading to false elevations 1

3. Missing the diagnosis by not considering ZES in patients with multiple or refractory peptic ulcers 4

4. Attributing symptoms to common peptic ulcer disease without investigating further when symptoms are refractory to standard treatment 3

In summary, the clinical presentation of multiple peptic ulcers refractory to PPI therapy combined with chronic diarrhea strongly points to Zollinger-Ellison syndrome, making serum gastrin level testing the most appropriate next diagnostic step.