THE TUMOR THAT DISGUISES ITSELF: A CLINICAL AND MOLECULAR REVIEW OF INSULINOMA
Keywords:
Insulinoma, Hypoglycemia, Whipple's Triad, Pancreatic Neuroendocrine Tumor, Multiple Endocrine Neoplasia type 1, Pancreatic Surgery, Targeted TherapyAbstract
Insulinoma, the most common functional pancreatic neuroendocrine tumor, poses a significant diagnostic challenge due to its insidious clinical presentation. This chapter provides a comprehensive review of the literature on insulinoma, addressing its epidemiology, the classic clinical manifestations encapsulated in Whipple's Triad, and the challenges posed by its neuroglycopenic symptoms, which often mimic neurological and psychiatric disorders, leading to diagnostic delays. The diagnostic methodology is detailed, from the gold standard of prolonged fasting testing for biochemical confirmation to the arsenal of imaging techniques for preoperative localization, including the evolution from anatomical to functional modalities, such as PET/CT with GLP-1 receptor analogs. The molecular pathogenesis is explored, contrasting the genetic pathways of sporadic insulinomas, often associated with mutations in the YY1 gene, with syndromic cases in the context of Multiple Endocrine Neoplasia type 1 (MEN1), driven by mutations in the MEN1 gene. Finally, therapeutic strategies are outlined, highlighting surgery as the curative approach for localized disease and the emergence of targeted molecular therapies, such as mTOR (everolimus) and tyrosine kinase (sunitinib) inhibitors, which have transformed the prognosis of malignant and metastatic disease.
