Is Octreotide Safe for the Management of Persistent Hyperinsulinemic Hypoglycemia of Infancy?

Introduction

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a glucose metabolic disorder characterized by profound hypoglycemia and inappropriate insulin secretion. It is also known as nesidioblastosis [1].

Neonates with PHHI run a high risk of severe neurological damage secondary to severe hypoglycemia unless immediate steps are taken to provide adequate management [2]. Management should include high glucose infusion and medical treatment with diazoxide and octreotide (somatostatin analogue). Pancreatectomy or resection of the focal lesion has to be performed as soon as possible, particularly in cases where medical treatment is not successful [3].

Octreotide is a synthetic analog of the hypothalamic release-inhibiting hormone Somatostatin [4]. The drug is licensed to treat bleeding from esophageal varices, to provide relief of symptoms in patients with neuroendocrine tumors, a reduction of complications following pancreatic surgery, and a reduction of vomiting in palliative care. It has been reported to be effective in treating chyle-rich effusions in children following cardiac surgery [5] [6]. Its beneficial effects in PHHI have been attributed to the inhibition of insulin release mediated through calcium channel inhibition [7].

Use of somatostatin and its analogs has recently been introduced into the management of PHHI. However, this relatively new treatment may have side effects and contraindications. We describe an association in a neonate treated with a somatostatin analog (octreotide) with subsequent necrotizing enterocolitis.

References

• 1 Aynsley-Green A. Nesidioblastosis of the pancreas in infancy.  Dev Med Child Neurol. 1981;  23 (3) 372-379
• 2 Schwitzgebel VM, Gitelman SE. Neonatal hyperinsulinism.  Clin Perinatol. 1998;  25 (4) 1015-1038 viii
• 3 Shilyansky J, Fisher S, Cutz E. et al . Is 95% pancreatectomy the procedure of choice for treatment of persistent hyperinsulinemic hypoglycemia of the neonate?.  J Pediatr Surg. 1997;  32 (2) 342-346
• 4 Lamberts SW, van der Lely AJ, de Herder WW. et al . Octreotide.  N Engl J Med. 1996;  334 (4) 246-254
• 5 Bhatia C, Pratap U, Slavik Z. Octreotide therapy: a new horizon in treatment of iatrogenic chyloperitoneum.  Arch Dis Child. 2001;  85 (3) 234-235
• 6 Pratap U, Slavik Z, Ofoe VD. et al . Octreotide to treat postoperative chylothorax after cardiac operations in children.  Ann Thorac Surg. 2001;  72 (5) 1740-1742
• 7 Bas F, Darendeliler F, Demirkol D. et al . Successful therapy with calcium channel blocker (nifedipine) in persistent neonatal hyperinsulinemic hypoglycemia of infancy.  J Pediatr Endocrinol Metab. 1999;  12 (6) 873-878
• 8 Glaser B, Landau H, Permutt MA. Neonatal hyperinsulinism.  Trends Endocrinol Metab. 1999;  10 (2) 55-61
• 9 Barrons RW. Octreotide in hyperinsulinism.  Ann Pharmacother. 1997;  31 (2) 239-241
• 10 Thornton PS, Alter CA, Katz LE. et al . Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism.  J Pediatr. 1993;  123 (4) 637-643
• 11 Stanley CA. Hyperinsulinism in infants and children.  Pediatr Clin North Am. 1997;  44 (2) 363-374
• 12 Simmons PS, Telander RL, Carney JA. et al . Surgical management of hyperinsulinemic hypoglycemia in children.  Arch Surg. 1984;  119 (5) 520-525
• 13 Christensen RD, Gordon PV, Besner GE. Can we cut the incidence of necrotizing enterocolitis in half – today?.  Fetal Pediatr Pathol. 2010;  29 (4) 185-198
• 14 Fitzgibbons SC, Ching Y, Yu D. et al . Mortality of necrotizing enterocolitis expressed by birth weight categories.  J Pediatr Surg. 2009;  44 (6) 1072-1075 discussion 5–6
• 15 Wiswell TE, Robertson CF, Jones TA. et al . Necrotizing enterocolitis in full-term infants. A case-control study.  Am J Dis Child. 1988;  142 (5) 532-535
• 16 Claud EC. Neonatal necrotizing enterocolitis – inflammation and intestinal immaturity.  Antiinflamm Antiallergy Agents Med Chem. 2009;  8 (3) 248-259
• 17 McElhinney DB, Hedrick HL, Bush DM. et al . Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes.  Pediatrics. 2000;  106 (5) 1080-1087
• 18 Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants.  Pediatrics. 2002;  109 (3) 423-428
• 19 Tyden G, Samnegard H, Thulin L. et al . Circulatory effects of somatostatin in anesthetized man.  Acta Chir Scand. 1979;  145 (7) 443-446
• 20 Laje P, Halaby L, Adzick NS. et al . Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism.  Pediatr Diabetes. 2010;  11 (2) 142-147

Correspondence