Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion.
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.
de Lonlay
Pascale
P
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
Simon-Carre
Aurore
A
Ribeiro
Maria-João
MJ
Boddaert
Nathalie
N
Giurgea
Irina
I
Laborde
Kathleen
K
Bellanné-Chantelot
Christine
C
Verkarre
Virginie
V
Polak
Michel
M
Rahier
Jacques
J
Syrota
André
A
Seidenwurm
David
D
Nihoul-Fékété
Claire
C
Robert
Jean-Jacques
JJ
Brunelle
Francis
F
Jaubert
Francis
F
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
D005462:Fluorine Radioisotopes; D007328:Insulin; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase