Abstract
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most important cause of hypoglycemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycemias, which require aggressive treatment to prevent severe and irreversible brain damage. A combination of glucose and glucagon is started as an emergency treatment as soon as a tentative diagnosis of PHHI is made. It is followed by treatment with diazoxide and other drugs and, finally, by pancreatectomy if the patient is drug resistant. PHHI is a heterogeneous disorder with two histopathological lesions, diffuse (DiPHHI) and focal (FoPHHI), which are clinically indistinguishable. FoPHHI is characterized by a somatic islet cell hyperplasia. DiPHHI corresponds to a functional abnormality of insulin secretion in the whole pancreas and involves several genes with different transmissions. The therapeutic outcome differs for both histological entities, as does genetic counseling.
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de Lonlay-Debeney P, Poggi-Travert F, Fournet JC et al. (1999) Clinical aspects and course of neonatal hype rinsulinism. N Engl J Med 340: 1169–1175
Stanley CA (1997) Hyperinsulinism in infants and children. Pediatr Clin North Am 44: 363–374
Bruining GJ (1990) Recent advances in hyperinsulinism and the pathogenesis of diabetes mellitus. Curr Opin Pediatr 2: 758–765
Thomas CG Jr, Underwood LE, Carney CN, Dolcourt JL, Whitt JJ (1977) Neonatal and infantile hypoglycemia due to insulin excess: new aspects of diagnosis and surgical management. Ann Surg 185: 505–517
Touati G, Poggi-Travert F, Ogier de Baulny H et al. (1998) Long-term treatment of persistent hyperinsulinaemic hypoglycaemia of infancy with diazoxide: a retrospective review of 77 cases and analysis of efficacy-predicting criteria. Eur J 26. Pediatr 157: 628–633
Stanley CA, Baker L (1976) Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia. Pediatrics 57: 702–711 27.
Chaussain JL, Georges P, Gendrel D, Donnadieu M, Job JC (1980) Serum branched-chain amino acids in the diagnosis of hyperinsulinism in infanncy. J Pediatr 97: 923–926 28.
Scarlett JA, Mako ME, Rubenstein AH et al. (1977) Factitious hypoglycemia. Diagnosis by measurement of serum C-peptide immunoreactivity and insulin-binding aantibodies. N Engl J Med 297: 1029–1032 29.
de Lonlay P, Cuer M, Barrot S et al. (1999) Hyperinsulinemic hypoglycemia as presenting symptom of Carbohydrate-Deficiency Glycoproteins. J Pediatr 135: 379–383
Thornton PS, Alter CA, Levitt Katz LE, Baker L, Stanley CA. (1993) Short-and long-term use of octreotide in the treatment of congenital hyperinsulinism. J Pediatr 123: 637–643
Stanley CA, Lieu Y, Hsu B et al. (1998) Hyperinsulinemia and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 338: 1352–1357
Shilyanski J, Fisher S, Cutz E, Perlman K, Filler RM (1997) Is pancreatectomy the procedure of choice for treatment of persistent hyperinsulinemic hypoglycemia of the neonate? J Pediatr Surg 32: 342–346
Spitz L, Bhargava RK, Grant DB, Leonard JV (1992) Surgical treatment of hyperinsulinaemic hypoglycaemia in infancy and childhood. Arch Dis Child 67: 201–205
de Lonlay P, Fournet JC, Rahier J et al. (1997) 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 100: 802–807
Verkarre V, Fournet JC, de Lonlay P et al. (1998) Maternal allele loss with somatic reduction to homozygosity of the paternally-inherited mutation of the SURI gene leads to congenital hyperinsulinism in focal islet cell adenomatous hyperplasia of the pancreas. J Clin Invest 102: 1286–1291
Sempoux C, Guiot Y, Lefevre A et al. (1998) Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis. J Clin Endocrinol Metab 83: 1455–1461
Klöppel G4 (1997) Nesidioblastosis. In: Soleia E, Capella C, Klöppel G (eds) Tumors of the pancreas. AFIP, Washington, PP 238–243
Goossens A, Gepts W, Saudubray JM et al. (1989) Diffuse and focal nesidioblastosis. A clinicopathological study of patients with persistent neonatal hyperinsulinemic hypoglycemia. Am J Surg Pathol 3: 766–775
Goudswaard WB, Houthoff HJ, Koudstaal J, Zwierstra RP (1986) Nesidioblastosis and endocrine hyperplasia of the pancreas: a secondary phenomenon. Hum Pathol 17: 46–53
Rahier J, Fält K, Müntefering H et al. (1984) The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells? Diabetologia 26: 282–289
Jaffé R, Hashida Y, Yunis EJ (1980) Pancreatic pathology in hyperinsulinemic hypoglycemia of infancy. Lab Invest 42: 356–365
R4ahier J, Sempoux C, Fournet JC et al. (1998) Partial or near-total pancreatectomy for persistent neonatal hyperinsulinaemic hypoglycaemia: the pathologist’s role. Histopathology 32: 15–19
Dubois J, Brunelle F, Touati G et al. (1995) Hyperinsulinism in children: diagnostic value of pancreatic venous sampling correlated with clinical, pathological and surgical outcome in 25 cases. Pediatr Radiol 25: 512–516
Kim H, Kerr A, Morehouse H (1995) The association between tuberous sclerosis and insulinoma. Am J Neuroradiol 16: 1543–1544
Cresto JC, Abdenur JP, Bergada I, Martino R (1998) Longterm follow up of persistent hyperinsulinaemic hypoglycaemia of infancy. Arch Dis Child 79: 440–444
Thornton PS, Sumner AE, Ruchelli ED et al. (1991) Familial and sporadic hyperinsulinism: histopathological findings and segregation analysis support a single autosomal recessive disorder. J Pediatr 119: 721–724
Thomas PM, Cote GJ, Wohllk N et al. (1995) Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 268: 426–429
Nestorowicz A, Wilson BA, Schoor KP et al. (1996) Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews. Hum Mol Genet 5: 1813–1822
Thomas P, Ye Y, Lightner E (1996) Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet 5: 1813–1822
Nestorowicz A, Inagaki N, Gonoi T et al. (1997) A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes 46: 1743–1748
Glaser B, Kesavan P, Heyman M et al. (1998) Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med 22: 226–230
Kukuvitis A, Deal C, Arbour L, Polychronakos C (1997) An autosomal dominant form of familial persistent hyperinsulinemic hypoglycemia of infancy, not linked to the sulfonylurea receptor. J Clin Endocrinol Metab 82: 1192–1194
Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332: 85–87
Demeure MJ, Klonoff DC, Karam JH, Duh QY, Clark OH (1991) Insulinomas associated with multiple endocrine neoplasia type 1: the need for a different surgical approach. Surgery 10: 998–1004
Bassett JH, Forbes SA, Pannett AA et al. (1998) Characterization of mutations in patients with multiple endocrine neoplasia type 1. Am J Hum Genet 62: 232–244
Agarwal SK, Kester MB, Debelenko LV et al. (1997) Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6: 1169–1175
Guru SC, Goldsmith PK, Burns AL et al. (1998) Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA 95: 1630–1634
Patel P, O’Rahilly S, Buckle V et al. (1990) Chromosome n allele loss in sporadic insulinoma. J Clin Pathol 43: 377–378
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de Lonlay, P., Saudubray, JM. (2000). Persistent Hyperinsulinemic Hypoglycemia. In: Fernandes, J., Saudubray, JM., Van den Berghe, G. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04285-4_9
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DOI: https://doi.org/10.1007/978-3-662-04285-4_9
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