Skip to main content
SpringerLink
Log in

Hypoglycemia

  • Chapter
  • First Online:
Pediatric Endocrinology

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  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.

    Article  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  4. Lord K, De Leon DD. Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. Int J Pediatr Endocrinol. 2013;2013(1):3.

    Article  Google Scholar 

  5. Stanley CA. Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders. J Clin Endocrinol Metab. 2016;101(3):815–26.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  28. Collins JE, Leonard JV. Hyperinsulinism in asphyxiated and small-for-dates infants with hypoglycaemia. Lancet (London, England). 1984;2(8398):311–3.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. Stanley CA. Dissecting the spectrum of fatty acid oxidation disorders. J Pediatr. 1998;132(3 Pt 1):384–6.

    Article  CAS  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Katherine Lord MD, Diva D. De León MD, MSCE & Charles A. Stanley MD

  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Katherine Lord MD, Diva D. De León MD, MSCE & Charles A. Stanley MD

  3. Congenital Hyperinsulinism Center, Philadelphia, PA, USA

    Katherine Lord MD, Diva D. De León MD, MSCE & Charles A. Stanley MD

  4. Division of Endocrinology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Katherine Lord MD, Diva D. De León MD, MSCE & Charles A. Stanley MD

Authors
  1. Katherine Lord MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diva D. De León MD, MSCE
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charles A. Stanley MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katherine Lord MD .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

    Sally Radovick

  2. Pediatric Endocrinology, Massachusetts General Hospital for Children, Boston, Massachusetts, USA

    Madhusmita Misra

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lord, K., De León, D.D., Stanley, C.A. (2018). Hypoglycemia. In: Radovick, S., Misra, M. (eds) Pediatric Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-73782-9_30

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-73782-9_30

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-73781-2

  • Online ISBN: 978-3-319-73782-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation