Spada F, Rossi R E, Modica R, Gelsomino F, Rinzivillo M, Rubino M, Pisa E, La Salvia Anna, Fazio N
Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.
Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Cancer Treat Rev. 2025 Apr;135:102907. doi: 10.1016/j.ctrv.2025.102907. Epub 2025 Feb 27.
Functioning neuroendocrine tumors (f-NETs) represent a minority of all NETs, however their management is challenging due to the impact on patients' survival and quality of life. In addition to f-NETs, paraneoplastic syndromes (PNS) are due to substances that are not related to the primary anatomical site, they can develop in different phases of NETs evolution, and might complicate the patient's clinical course. Dedicated guidelines are still scanty. We aim to review available literature on f-NETs to propose a useful tool for clinicians in order to improve the diagnostic process and the management.
Narrative review focused on f-NETs.
The most common f-NETs include insulinomas, gastrinomas and carcinoid syndrome (CS)- associated NETs. Symptoms related to hormone production may overlap with other common endocrine and gastrointestinal disorders, highlighting the pivotal role of multidisciplinary management. Somatostatin analogs (SSAs) represent the gold standard first-line treatment of most f-NETs, often followed by or combined with other treatments (surgery, liver-directed therapies, targeted therapies, peptide receptor radionuclide therapy). Paraneoplastic syndromes can develop in different phases of NET evolution and might complicate the patient's clinical course and response to therapy.
The management of hormonal syndromes is challenging and must be based on the multidisciplinary approach. Herein, we pointed out the minimal requirements for a NET specialist in the diagnosis and treatment of f-NETs. Efforts should be made to improve the awareness of functioning forms, to understand their pathogenesis and to improve their management.
功能性神经内分泌肿瘤（f-NETs）占所有神经内分泌肿瘤的少数，但由于其对患者生存和生活质量的影响，其管理具有挑战性。除f-NETs外，副肿瘤综合征（PNS）是由与原发解剖部位无关的物质引起的，它们可在NETs演变的不同阶段出现，并可能使患者的临床病程复杂化。专门的指南仍然很少。我们旨在回顾有关f-NETs的现有文献，为临床医生提出一个有用的工具，以改善诊断过程和管理。
针对f-NETs进行叙述性综述。
最常见的f-NETs包括胰岛素瘤、胃泌素瘤和类癌综合征（CS）相关的NETs。与激素产生相关的症状可能与其他常见的内分泌和胃肠道疾病重叠，突出了多学科管理的关键作用。生长抑素类似物（SSAs）是大多数f-NETs的金标准一线治疗方法，通常随后或与其他治疗方法（手术、肝脏定向治疗、靶向治疗、肽受体放射性核素治疗）联合使用。副肿瘤综合征可在NETs演变的不同阶段出现，并可能使患者的临床病程和对治疗的反应复杂化。
激素综合征的管理具有挑战性，必须基于多学科方法。在此，我们指出了NET专家在f-NETs诊断和治疗中的最低要求。应努力提高对功能性形式的认识，了解其发病机制并改善其管理。
