Abstract
Congenital hyperinsulinism is a leading cause of severe hypoglycaemia in the newborn period. There are two (diffuse and focal) histological subtypes of congenital hyperinsulinism. The diffuse form affects the entire pancreas and if medically unresponsive will require a near total (95%–98%) pancreatectomy. The focal form affects only a small region of the pancreas (with the rest of the pancreas being normal in endocrine and exocrine function) and only requires a limited pancreatectomy. This limited section of the focal lesion has the potential for curing the patient. Thus the pre-operative differentiation of these two subgroups is extremely important. Recent advances in Fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-DOPA PET/CT) have radically changed the clinical approach to patient with congenital hyperinsulinism. In most patients this novel imaging technique is able to offer precise pre-operative localisation of the focal lesion, thus guiding the extent of surgical resection.



References
Aynsley-Green A, Hussain K, Hall J, Saudubray JM, Nihoul-Fékété C, De Lonlay-Debeney P, et al. The Practical Management of Hyperinsulinism in Infancy. Arch Dis Child Fetal Neonatal Ed. 2000;82:F98–F107.
Kapoor RR, Flanagan SE, James C, Shield J, Ellard S, Hussain K. Hyperinsulinaemic hypoglycaemia. Arch Dis Child. 2009;94(6):450–7.
Hussain K, Aynsley-Green A, Stanley CA. Medications used in the treatment of hypoglycemia due to congenital hyperinsulinism of infancy (HI). Pediatr Endocrinol Rev. 2004;2 Suppl 1:163–7.
Mohnike K, Blankenstein O, Christesen HT, De Lonlay J, Hussain K, Koopmans KP, et al. Proposal for a standardized protocol for 18F-DOPA-PET (PET/CT) in congenital hyperinsulinism. Horm Res. 2006;66(1):40–2.
Rahier J, Guiot Y, Sempoux C. Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed. 2002;82(2):F108–12.
Thomas P, Ye Y, Lightner E. Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet. 1996;5(11):1809–12.
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(5209):426–9.
Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, et al. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes. 1997;46(11):1743–8.
Huopio H, Reimann F, Ashfield R, Komulainen J, Lenko HL, Rahier J, et al. Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1. J Clin Invest. 2000;106(7):897–906.
Pinney SE, MacMullen C, Becker S, Lin Y, Hanna C, Thornton P, et al. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. J Clin Invest. 2008;118(8):2877–86.
Flanagan SE, Kapoor RR, Banerjee I, Hall C, Smith VV, Hussain K, et al. Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia. Clin Genet. 2010 May 22.
Fékété CN, de Lonlay P, Jaubert F, Rahier J, Brunelle F, Saudubray JM. The surgical management of congenital hyperinsulinemic hypoglycemia in infancy. J Pediatr Surg. 2004;39(3):267–9.
Leibowitz G, Glaser B, Higazi AA, Salameh M, Cerasi E, Landau H. Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remission: high incidence of diabetes mellitus and persistent beta-cell dysfunction at long-term follow-up. J Clin Endocrinol Metab. 1995;80(2):386–92.
Sempoux C, Guiot Y, Jaubert F, Rahier J. Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis. Endocr Pathol. 2004;15(3):241–6.
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(7):1286–91.
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(6):2177–84.
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(4):802–7.
Damaj L, le Lorch M, Verkarre V, Werl C, Hubert L, Nihoul-Fékété C, et al. Chromosome 11p15 paternal isodisomy in focal forms of neonatal hyperinsulinism. J Clin Endocrinol Metab. 2008;93(12):4941–7.
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(1):288–96.
Ferry Jr RJ, Kelly A, Grimberg A, Koo-McCoy S, Shapiro MJ, Fellows KE, et al. Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism. J Pediatr. 2000;137(2):239–46.
Giurgea I, Laborde K, Touati G, Bellanné-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(2):925–9.
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(15):1169–75.
Otonkoski T, Näntö-Salonen K, Seppänen 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(1):13–8.
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(4):560–6.
Jager PL, Chirakal R, Marriott CJ, Brouwers AH, Koopmans KP, Gulenchyn KY. 6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications. J Nucl Med. 2008;49(4):573–86.
de Lonlay P, Simon-Carre A, Ribeiro MJ, Boddaert N, Giurgea I, Laborde K, et al. Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metab. 2006;91(3):933–40.
Koopmans KP, Neels ON, Kema IP, Elsinga PH, Links TP, de Vries EG, et al. Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results. Crit Rev Oncol Hematol. 2009;71(3):199–213.
Rodríguez MJ, Saura J, Finch CC, Mahy N, Billett EE. Localization of monoamine oxidase A and B in human pancreas, thyroid, and adrenal glands. J Histochem Cytochem. 2000;48(1):147–51.
Orlefors H, Sundin A, Fasth KJ, Oberg K, Långström B, Eriksson B. Bergström M 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(6):669–79.
Ericson LE, Håkanson R, Lundquist I. Accumulation of dopamine in mouse pancreatic B-cells following injection of L-DOPA. Localization to secretory granules and inhibition of insulin secretion. Diabetologia. 1977;13(2):117–24.
Ahrén B, Lundquist I. Effects of L-dopa-induced dopamine accumulation on 45Ca2+ efflux and insulin secretion in isolated rat islets. Pharmacology. 1985;30(2):71–82.
Barthlen W, Blankenstein O, Mau H, Koch M, Höhne C, Mohnike W, et al. Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography for surgery in focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2008;93(3):869–75. Epub 2007 Dec 11.
Cherubini V, Bagalini LS, Ianilli A, Marigliano M, Biagioni M, Carnielli V, et al. Rapid genetic analysis, imaging with 18F-DOPA-PET/CT scan and laparoscopic surgery in congenital hyperinsulinism. J Pediatr Endocrinol Metab. 2010;23(1–2):171–7.
Subramaniam RM, Karantanis D, Peller PJ. [18F]Fluoro-L-dopa PET/CT in congenital hyperinsulinism. J Comput Assist Tomogr. 2007;31(5):770–2.
Ribeiro MJ, Boddaert N, Bellanné-Chantelot C, Bourgeois S, Valayannopoulos V, Delzescaux T, et al. The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children. Eur J Nucl Med Mol Imaging. 2007;34(12):2120–8. Epub 2007 Jul 28.
Mohnike K, Blankenstein O, Minn H, Mohnike W, Fuchtner F, Otonkoski T. [18F]-DOPA positron emission tomography for preoperative localization in congenital hyperinsulinism. Horm Res. 2008;70(2):65–72.
Capito C, Khen-Dunlop N, Ribeiro MJ, Brunelle F, Aigrain Y, Crétolle C, et al. Value of 18F-fluoro-L-dopa PET in the preoperative localization of focal lesions in congenital hyperinsulinism. Radiology. 2009;253(1):216–22.
Arbizu Lostao J, Fernández-Marmiesse A, Garrastachu Zumarrán P, Martino Casado E, Azcona San Julián C, Carracedo A, et al. 18F-fluoro-L-DOPA PET-CT imaging combined with genetic analysis for optimal classification and treatment in a child with severe congenital hyperinsulinism. An Pediatr (Barc). 2008;68(5):481–5.
Hardy OT, Hernandez-Pampaloni M, Saffer JR, Suchi M, Ruchelli E, Zhuang H, et al. Diagnosis and localization of focal congenital hyperinsulinism by (18)F-Fluorodopa PET scan. J Pediatr. 2007;150(2):140–5.
Hardy OT, Hernandez-Pampaloni M, Saffer JR, Scheuermann JS, Ernst LM, Freifelder R, et al. Accuracy of [18F] fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2007;92(12):4706–11. Epub 2007 Sep 25.
Zani A, Nah SA, Ron O, Totonelli G, Ismail D, Smith VV, Ashworth M, et al. The Predictive Value of Preoperative 18Fluoro-L-DOPA-PET-CT Scans in Children with Congenital Hyperinsulinism of Infancy. J Pediatr Surg (2010) (in press).
Hussain K, Seppänen M, Näntö-Salonen K, Adzick NS, Stanley CA, Thornton P, et al. The diagnosis of ectopic focal hyperinsulinism of infancy with [18F]-dopa positron emission tomography. J Clin Endocrinol Metab. 2006;91(8):2839–42.
Peranteau WH, Bathaii SM, Pawel B, Hardy O, Alavi A, Stanley CA, et al. Multiple ectopic lesions of focal islet adenomatosis identified by positron emission tomography scan in an infant with congenital hyperinsulinism. J Pediatr Surg. 2007;42(1):188–92.
Kapoor RR, James C, Hussain K. Advances in the diagnosis and management of hyperinsulinemic hypoglycemia. Nat Clin Pract Endocrinol Metab. 2009;5(2):101–12.
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Ismail, D., Hussain, K. Role of 18F-DOPA PET/CT imaging in congenital hyperinsulinism. Rev Endocr Metab Disord 11, 165–169 (2010). https://doi.org/10.1007/s11154-010-9145-1
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DOI: https://doi.org/10.1007/s11154-010-9145-1