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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2007

01-12-2007 | Original article

The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Authors: Maria-João Ribeiro, Nathalie Boddaert, Christine Bellanné-Chantelot, Sandrine Bourgeois, Vassili Valayannopoulos, Thierry Delzescaux, Francis Jaubert, Claire Nihoul-Fékété, Francis Brunelle, Pascale De Lonlay

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2007

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Abstract

Purpose

Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [18F]fluoro-L-DOPA in distinguishing focal from diffuse HI.

Methods

Forty-nine children were studied with [18F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45–65 min after the injection of 4.2 ± 1.0 MBq/kg of [18F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI.

Results

We identified abnormal focal pancreatic uptake of [18F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance.

Conclusion

These data demonstrate that PET with [18F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI.
Literature
1.
Rahier J, Falt K, Muntefering H, Becker K, Gepts W, Falkmer S. The basic structural lesion of persistent neonatal hypoglycemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells? Diabetologia 1984;26:282–9.PubMedCrossRef
2.
Goossens A, Gepts W, Saudubray JM, Bonnefont JP, Nihoul-Fekete C, Heitz PU, et al. Diffuse and focal nesidioblastosis. A clinicopathological study of 24 patients with persistent neonatal hyperinsulinemic hypoglycemia. Am J Surg Pathol 1989;13:766–75.PubMedCrossRef
3.
Sempoux C, Guiot Y, Lefevre A, Nihoul-Fékété C, Jaubert F, Saudubray JM, et al. Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis. J Clin Endocrinol Metab 1988;83:1455–61.CrossRef
4.
Menni F, De Lonlay P, Sevin C, Touati G, Peigne C, Barbier V, et al. Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia. Pediatrics 2001;107:476–9.PubMedCrossRef
5.
Hirsch HJ, Loo S, Evans N, Crigler JF, Filler RM, Gabbay KH. Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin. N Engl J Med 1977;296:1323–6.PubMedCrossRef
6.
Glaser B, Hirsch HJ, Landau H. Persistent hyperinsulinemic hypoglycemia of infancy: long-term octreotide treatment without pancreatectomy. J Pediatr 1993;123:644–50.PubMedCrossRef
7.
Thornton PS, Alter CA, Katz LE, Baker L, Stanley CA. Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism. J Pediatr 1993;123:637–43.PubMedCrossRef
8.
De Lonlay-Debeney P, Poggi-Travert F, Fournet JC, Sempoux C, Vici CD, Brunelle F, et al. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med 1999;340:1169–75.PubMedCrossRef
9.
De Lonlay P, Fournet JC, Touati G, Groos MS, Martin D, Sevin C, et al. Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases. Eur J Pediatr 2002;161:37–48.PubMed
10.
Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995;268:426–9.PubMedCrossRef
11.
Nestorowicz A, Wilson BA, Schoor KP, Inoue H, Glaser B, Landau H, et al. Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews. Hum Mol Genet 1996;5:1813–22.PubMedCrossRef
12.
De Lonlay P, Fournet JC, Rahier J, Gross-Morand MS, Poggi-Travert F, Foussier V, et al. Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy. J Clin Invest 1997;100:802–7.PubMed
13.
Verkarre V, Fournet JC, De Lonlay P, Gross-Morand MS, Devillers M, Rahier J, et al. Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia. J Clin Invest 1998;102:1286–91.PubMedCrossRef
14.
Fournet JC, Mayaud C, De Lonlay P, Gross-Morand MS, Verkarre V, Castanet M, et al. Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11. Am J Pathol 2001;158:2177–84.PubMed
15.
De Lonlay P, Benelli C, Fouque F, Ganguly A, Aral B, Dionisi-Vici C, et al. Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. Pediatr Res 2001;50:353–7.PubMedCrossRef
16.
Filler RM, Weinberg MJ, Cutz E, Wesson DE, Ehrlich RM. Current status of pancreatectomy for persistent idiopathic neonatal hypoglycemia due to islet cell dysplasia. Prog Pediatr Surg 1991;26:60–75.PubMed
17.
Fekete CN, De Lonlay P, Jaubert F, Rahier J, Brunelle F, Saudubray. The surgical management of congenital hyperinsulinemic hypoglycemia in infancy. J Pediatr Surg 2004;39:267–9.PubMedCrossRef
18.
Thornton PS, MacMullen C, Ganguly A, Ruchelli E, Steinkrauss L, Crane A, et al. Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor. Diabetes 2003;52:2403–10.PubMedCrossRef
19.
Glaser B, Ryan F, Donath M, Landau H, Stanley CA, Baker L, et al. Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene. Diabetes 1999;48:1652–7.PubMedCrossRef
20.
Sempoux C, Guiot Y, Dahan K, Moulin P, Stevens M, Lambot V, et al. The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma. Diabetes 2003;52:784–94.PubMedCrossRef
21.
De Lonlay P, Giurgea I, Sempoux C, Touati G, Jaubert F, Rahier J, et al. Dominantly inherited hyperinsulinaemic hypoglycaemia. J Inherit Metab Dis 2005;28:267–76.PubMedCrossRef
22.
Brunelle F, Negre V, Barth MO, Fekete CN, Czernichow P, Saudubray JM, et al. Pancreatic venous samplings in infants and children with primary hyperinsulinism. Pediatr Radiol 1989;19:100–3.PubMedCrossRef
23.
Dubois J, Brunelle F, Touati G, Sebag G, Nuttin C, Thach T, et al. Hyperinsulinism in children: diagnostic value of pancreatic venous sampling correlated with clinical, pathological and surgical outcome in 25 cases. Pediatr Radiol 1995;25:512–6.PubMedCrossRef
24.
Chigot V, De Lonlay P, Nassogne MC, Laborde K, Delagne V, Fournet JC, et al. Pancreatic arterial calcium stimulation in the diagnosis and localisation of persistent hyperinsulinemic hypoglycaemia of infancy. Pediatr Radiol 2001;31:650–5.PubMedCrossRef
25.
Giurgea I, Laborde K, Touati G, Bellanne-Chantelot C, Nassogne MC, Sempoux C, et al. Acute insulin responses to calcium and tolbutamide do not differentiate focal from diffuse congenital hyperinsulinism. J Clin Endocrinol Metab 2004;89:925–9.PubMedCrossRef
26.
Stanley CA, Thornton PS, Ganguly A, MacMullen C, Underwood P, Bhatia P, et al. Preoperative evaluation of infants with focal or diffuse congenital hyperinsulinism by intravenous acute insulin response tests and selective pancreatic arterial calcium stimulation. J Clin Endocrinol Metab 2004;89:288–96.PubMedCrossRef
27.
Rodriguez MJ, Saura J, Finch CC, Mahy N, Billet EE. Localization of monoamine oxidase A and B in human pancreas, thyroid and adrenal glands. J Histochem Cytochem 2000;48:147–51.PubMed
28.
Orlefors H, Sundin A, Fasth KJ, Oberg K, Langstrom B, Eriksson B, et al. Demonstration of high monoaminoxidase-A levels in neuroendocrine gastroenteropancreatic tumors in vitro and in vivo—tumor visualization using positron emission tomography with 11C-harmine. Nucl Med Biol 2003;30:669–79.PubMedCrossRef
29.
Oei HK, Gazdar AF, Minna JD, Weir GC, Baylin SB. Clonal analysis of insulin and somatostatin secretion and L-dopa decarboxylase expression by a rat islet cell tumor. Endocrinology 1983;112:1070–5.CrossRef
30.
Lindstrom P. Aromatic-L-amino-acid decarboxylase activity in mouse pancreatic islets. Biochim Biophys Acta 1986;884:276–81.PubMed
31.
Borelli MI, Villar MJ, Orezzoli A, Gagliardino JJ. Presence of DOPA decarboxylase and its localisation in adult rat pancreatic islet cells. Diabetes Metab 1997;23:161–3.PubMed
32.
Ribeiro MJ, De Lonlay P, Delzescaux T, Boddaert N, Jaubert F, Bourgeois S, et al. Characterization of hyperinsulinism in infancy assessed with PET and 18F-fluoro-L-DOPA. J Nucl Med 2005;46:560–6.PubMed
33.
De Lonlay P, Simon-Carre A, Ribeiro MJ, Boddaert N, Giurgea I, Laborde K, et al. Congenital hyperinsulinism: pancreatic [18F]fluoro-L-DOPA positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metab 2006;291:933–40.
34.
Lemke AJ, Niehues SM, Hosten N, Amthauer H, Boehmig M, Stroszczynski C, et al. Retrospective digital image fusion of multidetector CT and 18F-FDG PET/ clinical value in pancreatic lesions—a prospective study with 104 patients. J Nucl Med 2004;45:1279–86.PubMed
35.
Hardy OT, Hernandez-Pampaloni M, Saffer JR, Suchi M, Ruchelli E, Zhuang H, et al. Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluodopa PET Scan. J Pediatr 2007;150:140–5.PubMedCrossRef
36.
Otonkoski T, Nanto-Salonen K, Seppanen M, Veijola R, Huopio H, Hussain K, et al. Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes 2006;55:13–8.PubMedCrossRef
37.
Gilbert JA, Frederick LM, Ames MM. The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin Cancer Res 2000;6:4365–72.PubMed
38.
Gilbert JA, Frederick LM, Pobst LJ, Ames MM. Hydrogen peroxide degradation and selective carbidopa-induced cytotoxicity against human tumor lines. Biochem Pharmacol 2005;69:1159–66.PubMedCrossRef
39.
Asplin CM, Paquette TL, Palmer JP. In vivo inhibition of glucagon secretion by paracrine beta cell activity in man. J Clin Invest 1981;68:314–8.PubMed
40.
Moens K, Berger V, Ahn JM, Van Schravendijk C, Hruby VJ, Pipeleers D, et al. Assessment of the role of interstitial glucagon in the acute glucose secretory responsiveness of in situ pancreatic beta-cells. Diabetes 2002;51:669–75.PubMedCrossRef
41.
Hussain K, Bryan J, Christesen HT, Brusgaard K, Aguilar-Bryan L. Serum glucagon counterregulatory hormonal response to hypoglycemia is blunted in congenital hyperinsulinism. Diabetes 2005;54:2946–51.PubMedCrossRef
Metadata
Title
The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children
Authors
Maria-João Ribeiro
Nathalie Boddaert
Christine Bellanné-Chantelot
Sandrine Bourgeois
Vassili Valayannopoulos
Thierry Delzescaux
Francis Jaubert
Claire Nihoul-Fékété
Francis Brunelle
Pascale De Lonlay
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0498-y

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