title: Acute insulin responses to calcium and tolbutamide do not differentiate focal from diffuse congenital hyperinsulinism.
abstract: Congenital hyperinsulinism (CHI) is related to two main histological pancreas anomalies: focal adenomatous hyperplasia and diffuse beta-cell hypersecretion. Pharmacological tests to measure acute insulin responses (AIR) to peripheral i.v. 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 Ca(2+) 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 beta-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.
authors.affiliation: Department of Pediatrics, Hôpital Necker Enfants Malades, 75743 Paris, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Giurgea
authors.forename: Kathleen
authors.initials: K
authors.lastname: Laborde
authors.forename: Guy
authors.initials: G
authors.lastname: Touati
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Marie-Cecile
authors.initials: MC
authors.lastname: Nassogne
authors.forename: Christine
authors.initials: C
authors.lastname: Sempoux
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Nguyen
authors.initials: N
authors.lastname: Khoa
authors.forename: Valerie
authors.initials: V
authors.lastname: Chigot
authors.forename: Jacques
authors.initials: J
authors.lastname: Rahier
authors.forename: Francis
authors.initials: F
authors.lastname: Brunelle
authors.forename: Claire
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: Charles
authors.initials: C
authors.lastname: Stanley
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Saudubray
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Robert
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
mesh_terms: D002125:Calcium Gluconate / Q000008:administration & dosage; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000145:classification* / Q000151:congenital / Q000175:diagnosis* / Q000378:metabolism; D007004:Hypoglycemic Agents; D007223:Infant; D007231:Infant, Newborn; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D014044:Tolbutamide
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D014044:Tolbutamide; D002125:Calcium Gluconate