Hyperinsulinism Treatment & Management
- Author: Sunil Sinha, MD; Chief Editor: Stephen Kemp, MD, PhD more...
Maintaining normoglycemia is essential to prevent neurologic sequelae. Infants with hyperinsulinism are at higher risk of neurologic sequelae than infants with hypoglycemia from other causes. Because insulin inhibits lipolysis and ketogenesis, hyperinsulinism results in the paucity of alternative fuel used by the brain.
The glucose output from the liver is 2-3 mg/kg/min in adults. Infants and children have a greater need for glucose and have a maximal output estimated at 5-7 mg/kg/min. Patients with hyperinsulinism may require very high glucose infusion rates (20-30 mg/kg/min) to maintain normoglycemia. Attempts should be made to keep blood glucose levels at 60 mg/dL or higher at all times.
Healthy neonates and infants can fast for 6 hours without experiencing hypoglycemia. This equates to skipping one feeding in the infant who is fed ad libitum.
Medications should be administered to suppress insulin secretion or stimulate glucose release.
Gastrostomy tube placement may be indicated in extreme cases to administer food if the infant is unable to handle the increased glucose requirements.
Partial or near-total pancreatectomy
Pancreatectomy is reserved for infants who fail to establish adequate control on medical therapy.
Although most surgeons initially remove 95% of the pancreas, a near-total (98%) pancreatectomy appears to be most effective in preventing hypoglycemia in the newborn period for those with diffuse potassium channel disease (SUR1 or Kir6.2 mutations). Remarkably, the elevated lifelong risk of diabetes mellitus is more closely related to the intrinsic error in regulated insulin release, rather than to the extent of pancreatectomy. One recent study showed almost 94% of focal hyperinsulinism cases required no further treatment, versus 41% with diffuse hyperinsulinism that showed continued hypoglycemia postoperatively.
Close monitoring of blood glucose levels is indicated to ensure glycemic control and to minimize hypoglycemia. If hypoglycemia persists, medical therapy should be reattempted. If medical therapy is unsuccessful, a second pancreatectomy may be indicated. The authors' experience indicates that clinically significant pancreatic regrowth can occur in infants after near-total pancreatectomy. A Whipple procedure is unwarranted because it cannot guarantee remission of diffuse disease.
Limited pancreatectomy is indicated for patients with focal disease.
Complications include pancreatic exocrine insufficiency, diabetes mellitus, and injury to the common bile duct.
See the list below:
- Pediatric endocrinologist
- Pediatric surgeon
- Geneticist (if family history is present or suspected)
- Closest tertiary referral center (academic children's hospital) for possible enrollment in clinical research protocols
Frequent feedings by gastrostomy help maintain euglycemia but do not prevent the need for intravenous dextrose administration before surgery.
Yorifuji T. Congenital hyperinsulinism: current status and future perspectives. Ann Pediatr Endocrinol Metab. 2014 Jun. 19 (2):57-68. [Medline].
Abdulhadi-Atwan M, Bushmann J, et al. Novel de novo mutation in sulfonylurea receptor 1 presenting as hyperinsulinism in infancy followed by overt diabetes in early adolescence. Diabetes. 2008 Jul. 57(7):1935-40. [Medline].
Arbizu Lostao J, Fernandez-Marmiesse A, Garrastachu Zumarran P, 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 May. 68(5):481-5. [Medline].
Glaser B, Kesavan P, Heyman M, et al. Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 1998. 338:226-30. [Medline].
Grimberg A, Ferry RJ Jr, Kelly A, et al. Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. Diabetes. 2001. 50:322-8. [Medline].
Shah JH, Maguire DJ, Munce TB, Cotterill A. Alanine in HI: a silent mutation cries out!. Adv Exp Med Biol. 2008. 614:145-50. [Medline].
Stanley CA, Baker L. The causes of neonatal hypoglycemia. N Engl J Med. 1999 Apr 15. 340(15):1200-1. [Medline].
Stanley CA, Lieu YK, Hsu BY, et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998. 338:1352-7. [Medline].
Suchi M, MacMullen CM, Thornton PS. Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism. Mod Pathol. 2006. 19:122-9. [Medline].
Thomas PM, Cote GJ, Wohllk N, et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995. 268:426-9. [Medline].
Hardy OT, Hernandez-Pampaloni M, Saffer JR, et al. Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2007. 92:4706-11. [Medline].
Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, et al. Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab. 2013 Feb. 98(2):E355-63. [Medline]. [Full Text].
Kapoor RR, Flanagan SE, Arya VB, Shield JP, Ellard S, Hussain K. Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. Eur J Endocrinol. 2013 Apr. 168(4):557-64. [Medline]. [Full Text].
Lord K, Radcliffe J, Gallagher PR, Adzick NS, Stanley CA, De León DD. High risk of diabetes and neurobehavioral deficits in individuals with surgically treated hyperinsulinism. J Clin Endocrinol Metab. 2015 Sep 1. jc20152539. [Medline].
Lord K, Dzata E, Snider KE, Gallagher PR, De León DD. Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases. J Clin Endocrinol Metab. 2013 Nov. 98(11):E1786-9. [Medline]. [Full Text].
Khawash P, Hussain K, Flanagan SE, Chatterjee S, Basak D. Nifedipine in Congenital Hyperinsulinism-A Case Report. J Clin Res Pediatr Endocrinol. 2015 Jun 5. 7 (2):151-4. [Medline].
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. 23:171-7. [Medline].
Craver RD, Hill CB. Cure of hypoglycemic hyperinsulinism by enucleation of a focal islet cell adenomatous hyperplasia. J Pediatr Surg. 1997. 32:1526-7. [Medline].
Cucchiaro G, Markowitz SD, Kaye R, et al. Blood glucose control during selective arterial stimulation and venous sampling for localization of focal hyperinsulinism lesions in anesthetized children. Anesth Analg. 2004. 99:1044-8, table of contents. [Medline].
[Guideline] De Leon DD, Stanley CA. Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2007. 3:57-68. [Medline].
de Lonlay-Debeney P, Poggi-Travert F, Fournet JC. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med. 1999. 340:1169-75. [Medline].
Ferry RJ Jr, Franklin SL, Geffner ME. Hypoglycemia. Kappy MS, Allen DB, Geffner ME, eds. Principles and Practice of Pediatric Endocrinology. Springfield, Ill: Charles C Thomas Publisher, Ltd; 2005. 607-34.
Ferry RJ Jr, Kelly A, Grimberg A, et al. Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism. J Pediatr. 2000. 137:239-46. [Medline].
Hoe FM, Thornton PS, Wanner LA. Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism. J Pediatr. 2006 Feb. 148(2):207-12. [Medline].
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 Nov. 2 Suppl 1:163-7. [Medline].
Kane C, Shepherd RM, Squires PE, et al. Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy. Nat Med. 1996. 2:1344-7. [Medline].
Levitt Katz LE, Satin-Smith MS, Collett-Solberg P, et al. Insulin-like growth factor binding protein-1 levels in the diagnosis of hypoglycemia caused by hyperinsulinism. J Pediatr. 1997 Aug. 131(2):193-9. [Medline].
Lovvorn HN III, Nance ML, Ferry RJ Jr. Congenital hyperinsulinism and the surgeon: lessons learned over 35 years. J Pediatr Surg. 1999. 34:786-92; discussion 792-3. [Medline].
Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin Chem. 2008. 54:256-63. [Medline].
Stanley CA. Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. Mol Genet Metab. 2004 Apr. 81 Suppl 1:S45-51. [Medline].
Steinkrauss L, Lipman TH, Hendell CD. Effects of hypoglycemia on developmental outcome in children with congenital hyperinsulinism. J Pediatr Nurs. 2005 Apr. 20(2):109-18. [Medline].
Suchi M, Thornton PS, Adzick NS, et al. Congenital hyperinsulinism: intraoperative biopsy interpretation can direct the extent of pancreatectomy. Am J Surg Pathol. 2004 Oct. 28(10):1326-35. [Medline].