Approach to the Patient: Insulinoma

Abstract

Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple 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. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. 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.

Keywords: hypoglycemia; insulin; insulinoma; pathology; therapy.

Figure 1.

Axial ⁶⁸Ga-exendin-PET/CT fused image of a 45-year-old man with documented endogenous hyperinsulinemic hypoglycemia (case 1) showing a 13 × 10-mm lesion (arrow) positive for the GLP-1 receptor and renal elimination of the tracer with uptake in the kidneys.

Figure 2.

Left: coronal CT image of a 50-year-old woman with documented endogenous hyperinsulinemic hypoglycemia (case 2) showing a 14 × 15-mm pancreatic lesion (box) and a gallbladder stone (arrow). Right: coronal ⁶⁸Ga-DOTATATE PET/CT fused images of a 50-year-old woman with documented endogenous hyperinsulinemic hypoglycemia (case 2) in the same plane as Fig. 2A showing a 14 × 15-mm PET-positive pancreatic lesion (box) and extensive ⁶⁸Ga-DOTATATE PET-positive liver metastases.

Figure 3.

Algorithm for clinical suspicion of insulinoma. After the diagnosis of hyperinsulinemic hypoglycemia, imaging procedures should be performed to locate the source of hyperinsulinism and hypoglycemia should be prevented by dietary and medical interventions. Following the detection of the localized or metastatic insulinoma, tumor-directed surgical and/or medical therapy should be initiated. GLP-1R, glucagon-like peptide-1 receptor; PRRT, peptide receptor radionuclide therapy; RFA, radiofrequency ablation; SSTR, somatostatin receptor.