An Updated Review of Zollinger–Ellison Syndrome: Integrating Biochemical Diagnosis, Tumor Biology, and Contemporary Management

Abstract

: Zollinger–Ellison syndrome (ZES) is a rare endocrine disorder caused by gastrin-secreting neuro endocrine tumors (gastrinomas) that result in excessive gastric acid production, leading to severe peptic ulcer disease, gastroesophageal reflux, chronic diarrhea, and malabsorption, which often delay diagnosis and complicate management. ZES occurs either sporadically or in association with multiple endocrine neoplasia type 1 (MEN1), further increasing diagnostic and therapeutic challenges due to overlapping clinical, biochemical, and pathological features. This literature review compiles and analyzes current evidence on the diagnostic criteria, patho morphological characteristics, biochemical markers, and treatment strategies for ZES, highlighting the roles of fasting serum gastrin levels, gastric acid secretion assessment, advanced imaging techniques, and histo pathological evaluation in achieving accurate diagnosis. Contemporary management approaches, including long-term proton pump inhibitor therapy, surgical intervention, and emerging targeted therapies, are discussed in relation to disease control and patient outcomes. This review uniquely integrates recent advances in diagnostic algorithms and molecular insights into gastrinoma biology with evolving therapeutic strategies, offering a concise yet comprehensive framework for early diagnosis and individualized management of ZES. By synthesizing updated multidisciplinary knowledge into a single narrative, this review aims to enhance clinical awareness, minimize diagnostic delays, and improve prognostic outcomes for patients with this rare but clinically significant syndrome.