Noninsulinoma pancreatogenous hypoglycemia: A novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes

In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably du e to insulinoma. In these patients with insulinoma, neuroglycopenic episode s exclusively after meal ingestion and negative 72-h fasts are extraordinar ily rare. We describe five adults with neuroglycopenic episodes from hyperi nsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fast s. Each had negative transabdominal ultrasonography, spiral computed tomogr aphic scanning, and celiac axis angiography of the pancreas. However, all s howed positive selective arterial calcium stimulation tests indicative of p ancreatic p-cell hyperfunction. At pancreatic exploration, no insulinoma wa s detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hy pertrophy and nesidioblastosis, but no insulinoma. No definite disease-caus ing mutation was detected in Kir6.2 and SUR1 genes, which encode the subuni ts of the pancreatic ATP-sensitive potassium channel responsible for glucos e-induced insulin secretion. Four patients who underwent gradient-guided pa rtial pancreatectomy have been free of hypoglycemic symptoms for up to 3 yr follow-up; the other, who underwent a limited distal pancreatectomy, has h ad brief recurrence of symptoms. The unique clinical features and responses to dynamic testing in these adults with hyperinsulinemic hypoglycemia in t he absence of insulinoma may constitute a new syndrome of postprandial hypo glycemia hom diffuse beta-cell hyperfunction.