Approach to the patient: Insulinoma.

Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms (panNEN) with an estimated incidence of 1-4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with Whipple's triad: 1) symptoms, signs, or both consistent with hypoglycemia, 2) a low plasma glucose measured at the time of the symptoms and signs, and 3) relief of symptoms and signs when the glucose is raised to normal. Non-metastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive". The 5-years-survival of patients with an indolent insulinoma has been reported to be 94-100% and for patients with an aggressive insulinoma this amounts to 24-67%. Five-10% of insulinomas are associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by CT is followed by EUS or magnetic resonance imaging (MRI) for indolent, localized insulinomas. Glucagon-like peptide 1 receptor (GLP-1R) PET/CT or PET/MRI is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for the control of the hypoglycemias. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, Everolimus, Sunitinib and cytotoxic chemotherapy can be valuable options.