Are Zollinger-Ellison Syndrome (ZES) and Gastrinoma the same condition?

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Are ZES and Gastrinoma the Same Condition?

No, Zollinger-Ellison Syndrome (ZES) and gastrinoma are not the same—gastrinoma is the tumor that causes ZES, while ZES is the clinical syndrome that results from the gastrin hypersecretion produced by that tumor. 1, 2

Understanding the Relationship

Gastrinoma is the cause; ZES is the effect. Specifically:

  • Gastrinoma is a gastrin-secreting neuroendocrine tumor, typically located in the duodenum or pancreas within the "gastrinoma triangle" 1, 2
  • Zollinger-Ellison Syndrome is the distinct clinical syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea that results from the gastrin-excess state caused by gastrinoma 2

Clinical Manifestations of ZES

The syndrome presents with specific symptoms driven by gastric acid hypersecretion:

  • Severe peptic ulceration refractory to standard therapy 3
  • Chronic diarrhea (occurring in approximately 50% at diagnosis) 1, 3
  • Gastroesophageal reflux disease refractory to standard therapy 1, 3
  • Epigastric pain lasting years despite acid-suppressive therapy (reported in 70% at diagnosis) 3
  • Weight loss 1

The Tumor Behind the Syndrome

Gastrinomas are subepithelial neuroendocrine tumors that arise from deeper layers, making standard mucosal biopsies non-diagnostic 1. Key characteristics include:

  • Location: The vast majority arise in the "gastrinoma triangle" involving parts of the duodenum, pancreas, and extra-hepatic biliary system 2
  • Malignant potential: High rate of malignancy, with metastases developing in 60% of gastrinoma patients, correlated to primary tumor size 1
  • Association with MEN-1: Type 2 gastric carcinoids develop in the setting of gastrinomas with hypergastrinemia and low gastric pH, and could be part of multiple endocrine neoplasia-1 syndrome 4

Diagnostic Distinction

The diagnosis requires both identifying the tumor and confirming the syndrome:

  • Biochemical confirmation of ZES: Fasting serum gastrin >1000 pg/mL combined with gastric pH <2 is diagnostic 5
  • Tumor identification: Gallium-68 radiotracers with positron emission tomography is currently the standard for tumor localization 1
  • Endoscopic evaluation: EUS has sensitivity up to 83% for pancreatic gastrinomas 1

Clinical Pitfall

Do not use these terms interchangeably in clinical documentation. A patient may have a gastrinoma without yet developing the full clinical syndrome of ZES if the tumor is detected early, or conversely, may present with ZES symptoms before the gastrinoma is localized on imaging 2, 6.

References

Guideline

Diagnosis and Management of Zollinger-Ellison Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnosis of Zollinger-Ellison Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Gastrin Level Evaluation and Clinical Indications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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