, Volume 26, Issue 4, pp 282–289 | Cite as

The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells?

  • J. Rahier
  • K. Fält
  • H. Müntefering
  • K. Becker
  • W. Gepts
  • S. Falkmer


Pancreatic tissue obtained at subtotal pancreatectomy from 15 infants with persistent hypoglycaemia with hyperinsulinism, and autopsy specimens from 23 age-matched normoglycaemic controls, were studied with morphometric methods after immunocytochemical staining of the four main islet cell types (A, B, D and pancreatic polypeptide cells). In three cases, a focal lesion was detected by gross examination. Macroscopic or microscopic examination did not distinguish the 12 other cases from controls. As found previously, nesidioblastosis was not a specific feature of the pancreas in infantile hypoglycaemia, being observed in age-matched controls as well. In cases with hypoglycaemia the volume density of B cells was not significantly increased; that of the A cells was within normal range. The volume density of pancreatic polypeptide cells was markedly augmented and that of somatostatin cells was significantly decreased. The mean nuclear volume of the B cells was increased by 40% in cases with diffuse changes, but in cases with a focal lesion this increase was restricted to the abnormal area. This finding is of decisive importance for diagnosis and has therapeutic implications. The increase in B-cell nuclear size is thought to reflect an enhanced functional activity of these cells. On the other hand, the figures obtained for the volume density of B and D cells must be viewed with some reservation because degranulation may interfere with accurate detection of these cells.

Key words

Persistent hypoglycaemia nesidioblastosis islet cells islet adenoma immunocytochemistry 


  1. 1.
    McQuarrie I (1954) Idiopathic spontaneously occuring hypoglycemia in infants. Clinical significance of problem and treatment. Am J Dis Child 87: 399–428Google Scholar
  2. 2.
    Laidlaw GF (1938) Nesidioblastoma, the islet tumor of the pancreas. Am J Pathol 14: 125–134Google Scholar
  3. 3.
    Brown RE, Young RB (1970) A possible role for the exocrine pancreas in the pathogenesis of neonatal leucine-sensitive hypoglycemia. Am J Dig Dis 15: 65–72Google Scholar
  4. 4.
    Yakovac WC, Baker L, Hummeler K (1971) Beta cell nesidioblastosis in idiopathic hypoglycemia of infancy. J Pediatr 79: 226–231Google Scholar
  5. 5.
    Grampa G, Gargantini L, Grigolato PG, Chiumello G (1974) Hypoglycemia in infancy caused by beta cell nesidioblastosis. Am J Dis Child 128: 226–231Google Scholar
  6. 6.
    Woo D, Scopes JW, Polak JM (1976) Idiopathic hypoglycemia in sibs with morphological evidence of nesidioblastosis of the pancreas. Arch Dis Child 51: 528–531Google Scholar
  7. 7.
    Thomas CG, 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: 505–517Google Scholar
  8. 8.
    Heitz PU, Klöppel G, Häcki WH, Polak JM, Pearse AGE (1977) Nesidioblastosis; the pathologic basis of persistent hyperinsulinemic hypoglycemia in infants: morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy. Diabetes 26: 632–642Google Scholar
  9. 9.
    Becker K, Wendel U, Przyrembel H, Tsotsalas M, Müntefering H, Bremer HJ (1978) Beta cell nesidioblastosis. Eur J Pediatr 127: 75–89Google Scholar
  10. 10.
    Dahms BB, Landing BH, Blaskovics M, Roe TF (1980) Nesidioblastosis and other islet cell abnormalities in hyperinsulinemic hypoglycemia of childhood. Hum Pathol 11: 641–649Google Scholar
  11. 11.
    Aynsley-Green A (1981) Nesidioblastosis of the pancreas in infancy. In: Randle PJ, Steiner DF, Whelan WJ (eds). Carbohydrate metabolism and its disorders. Academic Press, London, pp 181–204Google Scholar
  12. 12.
    Liechty RD, Alsever RN, Burrington J (1974) Islet cell hyperinsulinism in adults and children. JAMA 230: 1538–1543Google Scholar
  13. 13.
    Jaffe R, Hashida Y, Yunis EJ (1980) Pancreatic pathology in hyperinsulinemic hypoglycemia of infancy. Lab Invest 42: 356–365Google Scholar
  14. 14.
    Rahier J, Wallon J, Henquin JC (1981) Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia 20: 540–546Google Scholar
  15. 15.
    Gould VE, Memoli VA, Dardi LE, Gould NS (1981) Nesidiodysplasia and nesidioblastosis of infancy. Scand J Gastroent 16: 129–142Google Scholar
  16. 16.
    Karnauchow PN (1982) Nesidioblastosis in adults without insular hyperfunction. Am J Clin Pathol 78: 511–513Google Scholar
  17. 17.
    Gould VE, Memoli VA, Dardi LE, Gould NS (1983) Nesidiodysplasia and nesidioblastosis of infancy: structural and functional correlations with the syndrome of hyperinsulinemic hypoglycemia. Pediatr Pathol 1: 7–31Google Scholar
  18. 18.
    Sovik O, Vidnes J, Falkmer S (1975) Persistent neonatal hypoglycemia. Acta Pathol Microbiol Scand [A] 83: 155–166Google Scholar
  19. 19.
    Heitz PU, Klöppel G, Polak JM (1980) Morphology of the endocrine pancreas in persistent hypoglycaemia in infants. In: Andreani D, Lefevre PJ, Marks V (eds). Current views on hypoglycaemia and glucagon. Proceedings of the Serono Symposia, 1979, vol 30. Academic Press, London, pp 355–365Google Scholar
  20. 20.
    Bishop AE, Polak JM, Chesa PG, Timson CM, Bryant MG, Bloom SR (1981) Decrease of pancreatic somatostatin in neonatal nesidioblastosis. Diabetes 30: 122–126Google Scholar
  21. 21.
    Falkmer S, Sovik O, Vidnes J (1981) Immunohistochemical, morphometric, and clinical studies of the pancreatic islets in infants with persistent neonatal hypoglycemia of familial type with hyperinsulinism and nesidioblastosis. Acta Biol Med Germ 40: 39–54Google Scholar
  22. 22.
    Falkmer S, Rahier J, Sovik O, Vidnes J (1981) Significance of argyrophil parenchymal cells in the pancreatic islets in persistent neonatal hypoglycemia with hyperinsulinism of familial type. Upsala J Med Sci 86: 111–117Google Scholar
  23. 23.
    Shermeta DW, Mendelsohn G, Haller JA (1980) Hyperinsulinemic hypoglycemia of the neonate associated with persistent fetal histology and function of the pancreas. Ann Surg 191: 182–186Google Scholar
  24. 24.
    Schwartz JF, Zwiren GT (1971) Islet cell adenomatosis and adenoma in an infant. J Pediatr 79: 232–238Google Scholar
  25. 25.
    Fonkalsrud EW, Trout HH, Lippe B, La Franchi S, Dakake C (1974). Idiopathic hypoglycemia in infancy. Arch Surg 108: 801–804Google Scholar
  26. 26.
    Gabbay KH (1978) Case records of the Massachusetts General Hospital. New Engl J Med 299: 241–248Google Scholar
  27. 27.
    Sternberger LA (1979) Immunocytochemistry. John Wiley & Sons. New York, p 104Google Scholar
  28. 28.
    Rahier J, Goebbels RM, Henquin JC (1983). Cellular composition of the human diabetic pancreas. Diabetologia 24: 366–371Google Scholar
  29. 29.
    Wicksell SD (1925) The corpuscule problem. A mathematical study of a biometric problem. Biometrika 17: 84–89Google Scholar
  30. 30.
    Wicksell SD (1926) The corpuscule problem. Second memoire. Case of ellipsoidal corpuscules. Biometrika 18: 151–172Google Scholar
  31. 31.
    Baudhuin P (1968) L'analyse morphométrique quantitative des fractions subcellulaires. Thésis. Université Catholique de LouvainGoogle Scholar
  32. 32.
    Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. The Iowa State University Press. Ames, Iowa, USAGoogle Scholar
  33. 33.
    Moazam F, Rodgers BM, Talbert JL, Rosenbloom AL (1982) Near-total pancreatectomy in persistent infantile hypoglycemia. Arch Surg 117: 1151–1154Google Scholar
  34. 34.
    Kramer JL, Bell MJ, De Schryver K, Bower RJ, Ternberg JL, White NH (1982) Clinical and histologic indications for extensive pancreatic resection in nesidioblastosis. Am J Surg 143: 116–119Google Scholar
  35. 35.
    Aynsley-Green A, Polak JM, Bloom SR, Gough MH, Keeling J, Ashcroft SJH, Turner RC, Baum JD (1981) Nesidioblastosis of the pancreas: definition of the syndrome and the management of the severe neonatal hyperinsulinaemic hypoglycaemia. Arch Dis Child 56: 496–508Google Scholar
  36. 36.
    Floyd JC, Fajans SS, Pek S (1976) Regulation in healthy subjects of the secretion of human pancreatic polypeptide, a newly recognised pancreatic islet polypeptide. Trans Assoc Am Physicians 89: 146–158Google Scholar
  37. 37.
    Ehrie MG, Swartz FJ (1974) Diploid, tetraploid and octaploid beta cells in the islets of Langerhans of the normal human pancreas. Diabetes 23: 583–588Google Scholar
  38. 38.
    Haddad HM, Roberts WC, Pronove P, Bartter FC (1962) Leucine-induced hypoglycemia. New Engl J Med 267: 1057–1060Google Scholar
  39. 39.
    Misugi K, Misugi N, Sotos J, Smith B (1970) The pancreatic islet of infants with severe hypoglycemia. Arch Pathol 89: 208–220Google Scholar
  40. 40.
    Klöppel G, Altenähr E, Reichel W, Willig R Freytag G (1974) Morphometric and ultrastructural studies in an infant with leucine-sensitive hypoglycemia, hyperinsulinism and islet hyperplasia. Diabetologia 10: 245–252Google Scholar
  41. 41.
    Kracht J (1958) Morphologische Kriterien zur Beurteilung der Inselaktivität. Endokrinologie 36: 146–158Google Scholar
  42. 42.
    Bowen RE, Swartz FJ (1976) The ultrastructure of polyploid B-cells in the islets of normal mice. Diabetologia 12: 171–180Google Scholar
  43. 43.
    Hellman B, Hellerström C (1959) Size differences of the B-cell nuclei in the islet tissue of normal and alloxan-treated rats. Acta Pathol Microbiol Scand 45: 113–122Google Scholar
  44. 44.
    Wagner D, Richart R (1968) Polyploidy in the human endometrium with the Arias-Stella reaction. Arch Pathol 85: 475–480Google Scholar
  45. 45.
    Klöppel G, Altenähr E, Menke B (1975) The ultrastructure of focal islet cell adenomatosis in the newborn with hypoglycemia and hyperinsulinism; contribution to the classification of neonatal insulinomas. Virchows Arch [Path Anat] 366: 223–236Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • J. Rahier
    • 1
  • K. Fält
    • 3
  • H. Müntefering
    • 4
  • K. Becker
    • 4
  • W. Gepts
    • 2
  • S. Falkmer
    • 3
  1. 1.Department of PathologyUniversity Hospital St. Luc, University of Louvain in BrusselsBelgium
  2. 2.Department of PathologyFree University of BrusselsBrusselsBelgium
  3. 3.Department of PathologyUniversity of Lund, Malmö General HospitalMalmöSweden
  4. 4.Department of Paediatric PathologyInstitute of Pathology, Johannes Gutenberg UniversityMainzFRG

Personalised recommendations