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This version published online on January 10, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1713
A more recent version of this article appeared on March 1, 2006
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Submitted on August 1, 2005
Accepted on December 20, 2005

Congenital Hyperinsulinism: pancreatic [18F]Fluoro-L-DOPA Positron Emission Tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion

Pascale de Lonlay*, Aurore Simon-Carre, Maria-João Ribeiro, Nathalie Boddaert, Irina Giurgea, Kathleen Laborde, Christine Bellanné-Chantelot, Virginie Verkarre, Michel Polak, Jacques Rahier, André Syrota, David Seidenwurm, Claire Nihoul-Fékété, Jean-Jacques Robert, Francis Brunelle, and Francis Jaubert

Departments of Pediatrics, Biology, Radiology, Pathology, Pediatric Surgery, Hôpital Necker Enfants Malades, Université Paris-Descartes, Faculté de Médecine, Paris, France, ERM 0205 INSERM-CEA, Service Hospitalier Frédéric Joliot, DSV, DRM, Orsay, France; Department of Biology, Hôpital Saint-Antoine, Paris, France; Department of Pathology, University of Louvain, Faculty of Medicine, B-1200 Brussels, Belgium; Radiological Associates of Sacramento, Sutter Medical Center, Sacramento, California, USA

* To whom correspondence should be addressed. E-mail: pascale.delonlay{at}nck.aphp.fr.

Context. Congenital hyperinsulinism (HI) is characterized by hypoglycaemia 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 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.

Patients and methods. Pancreatic surgical specimens of 4 focal and 3 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 INS1 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 were 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 whatever INS-1 cells were treated by dopamine or Lodosyn® or untreated.

Conclusion. We validate PET with [18F]Fluoro-L-DOPA as a consistent test to differentiate diffuse and focal HI.




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