title: Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion.
abstract: BACKGROUND
  Congenital hyperinsulinism (HI) is characterized by hypoglycemia related to inappropriate insulin secretion. Focal and diffuse forms of hyperinsulinism share a similar clinical presentation, but their treatment is dramatically different. Preoperative differential diagnosis was based on pancreatic venous sampling, a technically demanding technique.
  
  
  OBJECTIVE
  Positron emission tomography (PET) after injection of [18F]fluoro-L-DOPA (L-dihydroxyphenylalanine) has been evaluated for the preoperative differentiation between focal and diffuse HI, by imaging uptake of radiotracer and the conversion of [18F]fluoro-L-dopa into dopamine by DOPA decarboxylase. We propose to validate this test by immunohistochemical approach.
  
  
  METHODS
  Pancreatic surgical specimens of four focal and three diffuse HI were studied, using anti-DOPA decarboxylase and proinsulin antibodies. The effect of an inhibitor of DOPA decarboxylase (carbidopa) on insulin secretion was evaluated in vivo and in cultured INS-1 cells.
  
  
  RESULTS
  Immunohistochemical detection of DOPA decarboxylase showed diffuse staining of Langerhans islets in the whole pancreas in all diffuse cases, in contrast with dense focal staining in all focal cases. Staining of Langerhans islets outside the focal lesion was diffusely but weakly positive. We correlated the localization of DOPA decarboxylase and proinsulin in normal pancreas and in both diffuse and focal HI tissues. The diffuse PET uptake found before treatment in one child with diffuse HI disappeared completely after carbidopa administration, suggesting in vivo that pancreatic cells can take up amine precursors and contain DOPA decarboxylase. The insulin secretion measured in the supernatant was the same whether INS-1 cells were treated by dopamine or Lodosyn or untreated.
  
  
  CONCLUSIONS
  We validate PET with as a consistent test to differentiate diffuse and focal HI.
authors.affiliation: Département de Pédiatrie, Hôpital Necker-Enfants Malades, Université Paris-Descartes, Faculté de Médecine, 149 rue de Sèvres, 75743 Paris cedex 15, France. pascale.delonlay@nck.aphp.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Aurore
authors.initials: A
authors.lastname: Simon-Carre
authors.forename: Maria-João
authors.initials: MJ
authors.lastname: Ribeiro
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Irina
authors.initials: I
authors.lastname: Giurgea
authors.forename: Kathleen
authors.initials: K
authors.lastname: Laborde
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
authors.forename: Jacques
authors.initials: J
authors.lastname: Rahier
authors.forename: André
authors.initials: A
authors.lastname: Syrota
authors.forename: David
authors.initials: D
authors.lastname: Seidenwurm
authors.forename: Claire
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Robert
authors.forename: Francis
authors.initials: F
authors.lastname: Brunelle
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
mesh_terms: D000293:Adolescent; D000818:Animals; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D006801:Humans; D006946:Hyperinsulinism / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D007150:Immunohistochemistry; D007223:Infant; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000473:pathology; D049268:Positron-Emission Tomography; D051381:Rats
chemical_list: D005462:Fluorine Radioisotopes; D007328:Insulin; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase