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Noninsulinoma Pancreatogenous Hypoglycemia: A Novel Syndrome of Hyperinsulinemic Hypoglycemia in Adults Independent of Mutations in Kir6.2 and SUR1 Genes¹

Division of Endocrinology and Metabolism (F.J.S., N.N.), Department of Surgery (G.B.T., C.S.G., J.A.v.H.), Department of Radiology (J.C.A.), Division of Cardiovascular Diseases (E.L., A.T.), and Department of Pathology (R.V.L.), Mayo Clinic and Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: F. John Service, M.D., Division of Endocrinology and Metabolism, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905.

In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably due to insulinoma. In these patients with insulinoma, neuroglycopenic episodes exclusively after meal ingestion and negative 72-h fasts are extraordinarily rare. We describe five adults with neuroglycopenic episodes from hyperinsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fasts. Each had negative transabdominal ultrasonography, spiral computed tomographic scanning, and celiac axis angiography of the pancreas. However, all showed positive selective arterial calcium stimulation tests indicative of pancreatic ß-cell hyperfunction. At pancreatic exploration, no insulinoma was detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hypertrophy and nesidioblastosis, but no insulinoma. No definite disease-causing mutation was detected in Kir6.2 and SUR1 genes, which encode the subunits of the pancreatic ATP-sensitive potassium channel responsible for glucose-induced insulin secretion. Four patients who underwent gradient-guided partial pancreatectomy have been free of hypoglycemic symptoms for up to 3 yr follow-up; the other, who underwent a limited distal pancreatectomy, has had brief recurrence of symptoms. The unique clinical features and responses to dynamic testing in these adults with hyperinsulinemic hypoglycemia in the absence of insulinoma may constitute a new syndrome of postprandial hypoglycemia from diffuse ß-cell hyperfunction.

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