Abstract
BACKGROUND: Functioning gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors that secrete biologically active hormones, leading to complex clinical syndromes such as carcinoid syndrome, VIPoma, glucagonoma, gastrinoma, insulinoma, and somatostatinoma. These syndromes frequently induce profound metabolic, gastrointestinal, and nutritional disturbances. OBJECTIVE: This review aims to provide a comprehensive overview of the physiopathology of malnutrition in functioning GEP-NENs and to highlight nutritional and supportive care strategies, including how medical, surgical, and locoregional treatments can indirectly improve nutritional outcomes. METHODS: We analyzed the current literature and clinical guidelines to identify key mechanisms of malnutrition across different functioning syndromes and their clinical manifestations. Nutritional recommendations and the impact of treatment modalities on nutritional status were summarized. RESULTS: The pathophysiology of malnutrition in functioning NENs is multifactorial and syndrome-specific. Hormonal hypersecretion may cause diarrhea, electrolyte imbalances, catabolic states, steatorrhea, or hypoglycemia, among other effects. These lead to nutrient loss, malabsorption, or altered intake. Tailored dietary interventions, micronutrient supplementation (e.g., niacin, calcium, vitamin B12), and symptom-guided nutritional support are essential. Somatostatin analogs, PRRT, and cytoreductive approaches often contribute to symptom control, thereby enhancing nutritional status and patient quality of life. CONCLUSIONS: Malnutrition in functioning GEP-NENs is a significant clinical issue that requires early recognition and a multidisciplinary, individualized management plan. Integrating nutrition into the comprehensive care of these patients is essential to improve outcomes and quality of life.