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Hypoglycemia

  • Katherine Lord
  • Diva D. De León
  • Charles A. Stanley
Chapter

Abstract

Hypoglycemia is a medical emergency that may result in seizures, permanent brain damage, or even sudden death. Because hypoglycemia can be the presenting sign of a large list of pathologies, it is necessary to have a comprehensive strategy for diagnosis. An approach based on the metabolic and endocrine systems involved in successful adaptation to fasting leads to timely diagnosis and treatment of hypoglycemia disorders. Suspected hypoglycemia should be evaluated through a closely monitored fasting test to obtain a critical sample when the plasma glucose is less than 50 mg/dL. To minimize the risk of neurologic damage, the therapeutic goal for children with hypoglycemic disorders is to maintain plasma glucoses above 70 mg/dL while encouraging normal feeding behavior.

Keywords

Hypoglycemia Hyperinsulinism Glycogen storage disease Neonate Hormones Glucose Insulin Glucagon Ketones Fasting 

References

  1. 1.
    Stanley CA, Rozance PJ, Thornton PS, De Leon DD, Harris D, Haymond MW, et al. Re-evaluating "transitional neonatal hypoglycemia": mechanism and implications for management. J Pediatr. 2015;166(6):1520–5.e1.CrossRefGoogle Scholar
  2. 2.
    Stanley CA, Baker L. Hypoglycemia. In: Kaye R, Oski FA, Barness LA, editors. Core textbook of pediatrics. Philadelphia: Lippincott; 1978. p. 280–305.Google Scholar
  3. 3.
    Finegold DN, Stanley CA, Baker L. Glycemic response to glucagon during fasting hypoglycemia: an aid in the diagnosis of hyperinsulinism. J Pediatr. 1980;96(2):257–9.CrossRefGoogle Scholar
  4. 4.
    Lord K, De Leon DD. Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. Int J Pediatr Endocrinol. 2013;2013(1):3.CrossRefGoogle Scholar
  5. 5.
    Stanley CA. Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders. J Clin Endocrinol Metab. 2016;101(3):815–26.CrossRefGoogle Scholar
  6. 6.
    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.CrossRefGoogle Scholar
  7. 7.
    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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 9.
    Pinney SE, MacMullen C, Becker S, Lin Y-W, 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.CrossRefGoogle Scholar
  10. 10.
    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.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    Lord K, Dzata E, Snider KE, Gallagher PR, De Leon DD. Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases. J Clin Endocrinol Metab. 2013;98(11):E1786–9.CrossRefGoogle Scholar
  13. 13.
    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(1):13–8.CrossRefGoogle Scholar
  14. 14.
    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.CrossRefGoogle Scholar
  15. 15.
    Weinzimer SA, Stanley CA, Berry GT, Yudkoff M, Tuchman M, Thornton PS. A syndrome of congenital hyperinsulinism and hyperammonemia. J Pediatr. 1997;130(4):661–4.CrossRefGoogle Scholar
  16. 16.
    Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998;338(19):1352–7.CrossRefGoogle Scholar
  17. 17.
    Kelly A, Ng D, Ferry RJ Jr, Grimberg A, Koo-McCoy S, Thornton PS, et al. Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. J Clin Endocrinol Metab. 2001;86(8):3724–8.CrossRefGoogle Scholar
  18. 18.
    Bahi-Buisson N, Roze E, Dionisi C, Escande F, Valayannopoulos V, Feillet F, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50(12):945–9.CrossRefGoogle Scholar
  19. 19.
    Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, et al. Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 1998;338(4):226–30.CrossRefGoogle Scholar
  20. 20.
    Li C, Chen P, Palladino A, Narayan S, Russell LK, Sayed S, et al. Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenase. J Biol Chem. 2010;285(41):31806–18.CrossRefGoogle Scholar
  21. 21.
    Clayton PT. Hyperinsulinism in short-chain l-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Investig. 2001;108(3):457–65.CrossRefGoogle Scholar
  22. 22.
    Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 2007;4(4):e118.CrossRefGoogle Scholar
  23. 23.
    Kapoor RR, Locke J, Colclough K, Wales J, Conn JJ, Hattersley AT, et al. Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes. 2008;57(6):1659–63.CrossRefGoogle Scholar
  24. 24.
    Stanescu DE, Hughes N, Kaplan B, Stanley CA, De Leon DD. Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab. 2012;97(10):E2026–30.CrossRefGoogle Scholar
  25. 25.
    Meissner T, Otonkoski T, Feneberg R, Beinbrech B, Apostolidou S, Sipila I, et al. Exercise induced hypoglycaemic hyperinsulinism. Arch Dis Child. 2001;84(3):254–7.CrossRefGoogle Scholar
  26. 26.
    Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, et al. Physical exercise–induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic β cells. Am J Hum Genet. 2007;81(3):467–74.CrossRefGoogle Scholar
  27. 27.
    González-Barroso MM, Giurgea I, Bouillaud F, Anedda A, Bellanné-Chantelot C, Hubert L, et al. Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion. PLoS One. 2008;3(12):e3850.CrossRefGoogle Scholar
  28. 28.
    Collins JE, Leonard JV. Hyperinsulinism in asphyxiated and small-for-dates infants with hypoglycaemia. Lancet (London, England). 1984;2(8398):311–3.CrossRefGoogle Scholar
  29. 29.
    Hoe FM, Thornton PS, Wanner LA, Steinkrauss L, Simmons RA, Stanley CA. Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism. J Pediatr. 2006;148(2):207–12.CrossRefGoogle Scholar
  30. 30.
    Kalish JM, Boodhansingh KE, Bhatti TR, Ganguly A, Conlin LK, Becker SA, et al. Congenital hyperinsulinism in children with paternal 11p uniparental isodisomy and Beckwith-Wiedemann syndrome. J Med Genet. 2016;53(1):53–61.CrossRefGoogle Scholar
  31. 31.
    Kelly A, Tang R, Becker S, Stanley CA. Poor specificity of low growth hormone and cortisol levels during fasting hypoglycemia for the diagnoses of growth hormone deficiency and adrenal insufficiency. Pediatrics. 2008;122(3):e522–e8.CrossRefGoogle Scholar
  32. 32.
    Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med: Official Journal of the American College of Medical Genetics. 2014;16(11):e1.CrossRefGoogle Scholar
  33. 33.
    Stanley CA, Bennett MJ. Disorders of mitochondrial fatty acid beta-oxidation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson textbook of pediatrics. 18th ed. Philadelphia: W.B. Saunders; 2007. p. 567–73.Google Scholar
  34. 34.
    Stanley CA. Dissecting the spectrum of fatty acid oxidation disorders. J Pediatr. 1998;132(3 Pt 1):384–6.CrossRefGoogle Scholar
  35. 35.
    Stanley CA, Coates PM. Inherited defects of fatty acid oxidation which resemble Reye's syndrome. In: Pollack JD, editor. Reye's syndrome IV. Bryan: NRSF; 1985.Google Scholar
  36. 36.
    Ziadeh R, Hoffman EP, Finegold DN, Hoop RC, Brackett JC, Strauss AW, et al. Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies. Pediatr Res. 1995;37(5):675–8.CrossRefGoogle Scholar
  37. 37.
    Weinstein DA, Correia CE, Saunders AC, Wolfsdorf JI. Hepatic glycogen synthase deficiency: an infrequently recognized cause of ketotic hypoglycemia. Mol Genet Metab. 2006;87(4):284–8.CrossRefGoogle Scholar
  38. 38.
    van Hasselt PM, Ferdinandusse S, Monroe GR, Ruiter JP, Turkenburg M, Geerlings MJ, et al. Monocarboxylate transporter 1 deficiency and ketone utilization. N Engl J Med. 2014;371(20):1900–7.CrossRefGoogle Scholar
  39. 39.
    Samuk I, Afriat R, Horne T, Bistritzer T, Barr J, Vinograd I. Dumping syndrome following Nissen fundoplication, diagnosis, and treatment. J Pediatr Gastroenterol Nutr. 1996;23(3):235–40.CrossRefGoogle Scholar
  40. 40.
    Palladino AA, Sayed S, Levitt Katz LE, Gallagher PR, De Leon DD. Increased glucagon-like peptide-1 secretion and postprandial hypoglycemia in children after Nissen fundoplication. J Clin Endocrinol Metab. 2009;94(1):39–44.CrossRefGoogle Scholar
  41. 41.
    Ng DD, Ferry RJ Jr, Kelly A, Weinzimer SA, Stanley CA, Katz LE. Acarbose treatment of postprandial hypoglycemia in children after Nissen fundoplication. J Pediatr. 2001;139(6):877–9.CrossRefGoogle Scholar
  42. 42.
    Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr. 2015;167:238.CrossRefGoogle Scholar
  43. 43.
    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(3):476–9.CrossRefGoogle Scholar
  44. 44.
    Steinkrauss L, Lipman TH, Hendell CD, Gerdes M, Thornton PS, Stanley CA. Effects of hypoglycemia on developmental outcome in children with congenital hyperinsulinism. J Pediatr Nurs. 2005;20(2):109–18.CrossRefGoogle Scholar
  45. 45.
    Ludwig A, Ziegenhorn K, Empting S, Meissner T, Marquard J, Holl R, et al. Glucose metabolism and neurological outcome in congenital hyperinsulinism. Semin Pediatr Surg. 2011;20(1):45–9.CrossRefGoogle Scholar
  46. 46.
    Lord K, Radcliffe J, Gallagher PR, Adzick NS, Stanley CA, De Leon DD. High Risk of Diabetes and Neurobehavioral Deficits in Individuals with Surgically Treated Hyperinsulinism. J Clin Endocrinol Metab. 2015;100(11):4133–9.CrossRefGoogle Scholar
  47. 47.
    Dayton PG, Pruitt AW, Faraj BA, Israili ZH. Metabolism and disposition of diazoxide. A mini-review. Drug Metab Dispos. 1975;3(3):226–9.PubMedGoogle Scholar
  48. 48.
    Laje P, Halaby L, Adzick NS, Stanley CA. Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism. Pediatr Diabetes. 2010;11(2):142–7.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Katherine Lord
    • 1
    • 2
    • 3
    • 4
  • Diva D. De León
    • 1
    • 2
    • 3
    • 4
  • Charles A. Stanley
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of PediatricsThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Congenital Hyperinsulinism CenterPhiladelphiaUSA
  4. 4.Division of EndocrinologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA

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