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Acute Insulin Responses to Calcium and Tolbutamide Do Not Differentiate Focal from Diffuse Congenital Hyperinsulinism

Departments of Pediatrics (I.G., G.T., M.-C.N., J.-M.S., J.-J.R., P.d.L.), Physiology (K.L.), Pathology (F.J.), Biochemistry A (N.K.), Radiology (V.C., F.B.), and Pediatric Surgery (C.N.-F.), Hôpital Necker Enfants Malades, 75743 Paris, France; Department of Biology (C.B.-C.), Hôpital Saint-Antoine, 75012 Paris, France; Department of Pathology (C.Se., J.R.), Université de Louvain, B-1349 Louvain-La-Neuve, Belgium; Division of Physiology and Pharmacology (M.J.D.), School of Biological Science, The University of Manchester, M-139 PL Manchester, United Kingdom; and Department of Pediatrics (C.St.), The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4399

Congenital hyperinsulinism (CHI) is related to two main histological pancreas anomalies: focal adenomatous hyperplasia and diffuse ß-cell hypersecretion. Pharmacological tests to measure acute insulin responses (AIR) to peripheral iv injections of glucose, calcium, and tolbutamide have been reported as potential means to distinguish between these histological forms. In patients with defects in ATP-sensitive potassium channels, tolbutamide will fail to induce insulin release in affected portions of the pancreas, whereas calcium gluconate will enhance insulin release through spontaneously active voltage-gated Ca²⁺ channels. Consequently, in focal CHI patients, calcium should promote AIRs from the lesion, whereas tolbutamide should act to promote insulin secretion from the healthy region of the pancreas (outside the focal hyperplasia). We therefore studied AIRs to calcium and tolbutamide stimulation tests in 16 children with focal (n = 9) or diffuse (n = 7) CHI before pancreatic surgery. We found hypervariable AIRs to glucose and calcium stimulation in both focal and diffuse CHI patients. AIRs to tolbutamide stimulation were found modest in focal CHI patients, which might account for ß-cell quiescence in the healthy portion of the pancreas of these patients. We conclude that AIRs to calcium and tolbutamide stimulation tests are not sufficient to differentiate the focal from the diffuse CHI patients.

Address all correspondence and requests for reprints to: Dr. Pascale de Lonlay, Fédération de Pédiatrie, Hôpital Necker–Enfants Malades, 149 rue de Sèvres, 75743 Paris cedex 15, France. E-mail: pascale.delonay{at}nck.ap-hop-paris.fr.

Collaborative interactions were funded by a European Community–funded Concerted Action Grant (QLG1-2000-00513). I.G. is a grant recipient from AJP-Laboratories Gallia.

Abbreviations: AIR, Acute insulin response; CaAIR, acute insulin response to peripheral iv calcium gluconate stimulation; CHI, congenital hyperinsulinism; IVGTT, iv glucose tolerance test; K_ATP, ATP-sensitive potassium; PACS, pancreatic arterial calcium stimulation; PVS, pancreatic venous sampling.

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