What are the signs, symptoms, assessment findings, and diagnostics associated with gastrinomas?

Gastrinoma: Clinical Presentation and Diagnostic Approach

Signs and Symptoms

Gastrinoma should be suspected in patients presenting with severe gastroduodenal ulcer symptoms (dyspepsia) accompanied by diarrhea, particularly when peptic ulcers are recurrent and occur in the absence of Helicobacter pylori infection. 1

Classic Clinical Features:

• Recurrent peptic ulcer disease with or without gastrointestinal bleeding 1, 2
• Chronic diarrhea (often watery) that may precede ulcer symptoms 1, 3, 2
• Gastroesophageal reflux disease (GERD) symptoms that are severe and refractory to standard therapy 3, 2
• Weight loss and fatigue in chronic cases 3
• Symptoms are often nonspecific, leading to diagnostic delays averaging >5 years from symptom onset 2

Critical History and Assessment Findings

Family History

• Evaluate for Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome in all patients with suspected gastrinoma 1
• Gastrinoma is one of the most common pancreatic neuroendocrine tumors in MEN1 patients 1
• MEN1-associated gastrinomas are typically multiple and located in the duodenum (approximately 70% of cases) 1

Medication History

• Document proton pump inhibitor (PPI) use, as these medications confound diagnosis by elevating both gastrin and chromogranin A levels 1, 4
• H2 antagonist use also elevates gastrin and chromogranin A 1

Diagnostic Testing Algorithm

Step 1: Biochemical Confirmation

Measure fasting serum gastrin levels AFTER discontinuing PPIs for at least 1 week (ideally 10-14 days). 1, 4 This is the most critical step, as most patients with elevated gastrin do NOT have gastrinoma but rather achlorhydria or are on acid-suppressing medications 1.

Diagnostic Criteria:

• Fasting gastrin >10 times upper limit of normal PLUS gastric pH <2 is diagnostic 1
• Gastrin >1000 pg/mL with gastric pH <2 is considered diagnostic 2
• For equivocal cases, secretin stimulation test should be performed 1

Critical Pitfall:

PPIs must be stopped with great caution and only under supervision, as it is dangerous for patients with gastrinoma to abruptly discontinue acid suppression. 1 Oral H2 antagonists may be substituted during the washout period, but should be stopped 48 hours before testing 1.

Step 2: Chromogranin A Measurement

• Serum chromogranin A is elevated in gastrinoma but is NOT specific 1
• Chromogranin A is elevated in 60% or more of pancreatic neuroendocrine tumors 1, 5
• False elevations occur with: PPI use, renal failure, liver failure, hypertension, chronic gastritis, and atrophic gastritis 1, 5, 4

Step 3: Rule Out Atrophic Gastritis

Upper gastrointestinal endoscopy with gastric biopsy is ALWAYS required to differentiate gastrinoma from autoimmune atrophic gastritis, as both conditions cause elevated gastrin and chromogranin A 1. Additionally, assess for and eradicate H. pylori 1.

Step 4: Intragastric pH Measurement

• Measure gastric pH to confirm gastric acid hypersecretion 1
• pH <2 in the setting of elevated gastrin supports gastrinoma diagnosis 1, 2
• Esophageal pH recording may be useful in selected cases 2

Step 5: Imaging for Tumor Localization

Multiphasic contrast-enhanced CT or MRI of the abdomen and pelvis is the recommended initial imaging modality. 1, 5, 4

Additional Imaging Modalities:

• Somatostatin receptor scintigraphy (Octreoscan) to detect tumors missed by CT/MRI and assess for metastatic disease 1, 5
• Endoscopic ultrasound (EUS) is particularly useful for small duodenal gastrinomas, which are the most common location (approximately 70% of gastrinomas) 1, 6

Step 6: MEN1 Syndrome Screening

All patients with gastrinoma should be evaluated for MEN1 syndrome by measuring fasting calcium, parathyroid hormone, and prolactin 1.

Tumor Location and Prognosis

• Most gastrinomas (approximately 70%) are located in the duodenum, not the pancreas 1, 6
• Duodenal gastrinomas are typically small and may be multiple in MEN1 patients 1, 7, 6
• 80-90% of gastrinomas have metastatic potential 1, 8
• Duodenal gastrinomas have better prognosis than pancreatic gastrinomas, progressing more slowly to liver metastases despite early lymph node involvement 7, 6
• Liver metastases are associated with decreased survival 8

Key Diagnostic Pitfalls to Avoid

• Do not interpret gastrin levels while patient is on PPIs or H2 antagonists - this is the most common cause of diagnostic error 1, 4
• Do not diagnose gastrinoma based on immunohistochemical gastrin positivity alone without clinical evidence of Zollinger-Ellison syndrome 7
• Do not assume all elevated gastrin is gastrinoma - achlorhydria and atrophic gastritis are far more common causes 1
• Hormone-secreting tumors may cause significant symptoms even when very small, making lesion identification difficult 1