World Journal of Surgery

, Volume 28, Issue 12, pp 1227–1230 | Cite as

Nesidioblastosis: An Old Term and a New Understanding



Nesidioblastosis is a clinically, pathologically, and genetically heterogeneous disease. Differences between well described forms in neonates with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and rare forms in adults are described. Histopathologic criteria include hypertrophic islets occasionally showing beta cells with pleomorphic nuclei, ductuloinsular complexes, and neoformation of islets from ducts. These changes can be found as diffuse or focal forms of nesidioblastosis. Although most cases occur sporadically, several genetic defects (SUR1, Kir6.2, GCK, and GLUD1 genes) have been described in neonates. In adults a higher rate of nesidioblastosis is observed in conjunction with multiple endocrine neoplasia type 1. The disease is diagnosed biochemically by a supervised fasting test in adults and in neonates by determining the glucose requirements to maintain normoglycemia, inappropriately high insulin and c-peptide levels, low free fatty acid and ketone body concentrations, glycemic response to glucagons, and the absence of ketonuria. If all highly selective noninvasive imaging techniques fail to identify a tumor, selective arterial calcium stimulation testing for gradient-guided surgery in adults and percutaneous transhepatic pancreatic venous sampling in neonates should be performed. a 95% pancreatectomy is necessary in neonates with a diffuse form of nesidioblastosis, whereas focal forms can be treated by partial pancreatectomy.


  1. 1.
    Laidlaw, GF 1938Nesidioblastoma, the islet cell tumor of the pancreasAm. J. Pathol.14125134Google Scholar
  2. 2.
    Service, FJ, Natt, N, Thompson, GB,  et al. 1999Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genesJ. Clin. Endocrinol. Metab.8415821589CrossRefPubMedGoogle Scholar
  3. 3.
    Thompson, GB, Service, FJ, Andrews, JC,  et al. 2000Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patientsSurgery128937945CrossRefPubMedGoogle Scholar
  4. 4.
    Kaczirek, K, Soleiman, A, Schindl, M,  et al. 2003Nesidioblastosis in adults: a challenging cause of organic hyperinsulinismEur. J. Clin. Invest.33488492CrossRefPubMedGoogle Scholar
  5. 5.
    Aynsley-Green, A, Hussain, K, Hall, J,  et al. 2000Practical management of hyperinsulinism in infancyArch. Dis. Child. Fetal Neonatal Ed.82F98F107Google Scholar
  6. 6.
    Goudswaard, WB, Houthoff, HJ, Koudstaal, J,  et al. 1986Nesidioblastosis and endocrine hyperplasia of the pancreas: a secondary phenomenonHum. Pathol.174654PubMedGoogle Scholar
  7. 7.
    Walmsley, D, Matheson, NA, Ewen, S,  et al. 1995Nesidioblastosis in an elderly patientDiabet. Med.12542545PubMedGoogle Scholar
  8. 8.
    Harrison, TS, Fajans, SS, Floyd, JC,Jr,  et al. 1984Prevalence of diffuse pancreatic beta islet cell disease with hyperinsulinism: problems in recognition and managementWorld J. Surg.8583589PubMedGoogle Scholar
  9. 9.
    Lee, WL, Won, JG, Chiang, JH,  et al. 1997Selective intra-arterial calcium injection in the investigation of adult nesidioblastosis: a case reportDiabet. Med.14985988CrossRefPubMedGoogle Scholar
  10. 10.
    Weinstock, G, Margulies, P, Kahn, E,  et al. 1986Islet cell hyperplasia: an unusual cause of hypoglycemia in an adultMetabolism35110117CrossRefPubMedGoogle Scholar
  11. 11.
    Reineckelüthge, AKF, Klöppel, G 2000The molecular basis of persistent hyperinsulinemic hypoglycemia of infancy and its pathologic substratesVirchows Arch.43615Google Scholar
  12. 12.
    Lloyd RV, Douglas BR, William F, et al. (2002) Diffuse neuroendocrine system/nesidioblastosis in adults. In Atlas of Nontumor Pathology, Washington, DC, American Registry of Pathology and the Armed Forces Institute of Pathology, pp 287–291Google Scholar
  13. 13.
    Glaser, B, Chiu, KC, Anker, R,  et al. 1994Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin geneNat. Genet.7185188CrossRefPubMedGoogle Scholar
  14. 14.
    Stanley, CA, Lieu, YK, Hsu, BY,  et al. 1998Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase geneN. Engl. J. Med.33813521357CrossRefPubMedGoogle Scholar
  15. 15.
    Glaser, B, Kesavan, P, Heyman, M,  et al. 1998Familial hyperinsulinism caused by an activating glucokinase mutationN. Engl. J. Med.338226230CrossRefPubMedGoogle Scholar
  16. 16.
    Lonlay, P, Fournet, JC, Rahier, J,  et al. 1997Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomyJ. Clin. Invest.100802807PubMedGoogle Scholar
  17. 17.
    Servicet, FJ 1995Hypoglycemic disordersN. Engl. J. Med.33211441152CrossRefPubMedGoogle Scholar
  18. 18.
    Lonlay-Debeney, P, Poggi-Travert, F, Fournet, JC,  et al. 1999Clinical features of 52 neonates with hyperinsulinismN. Engl. J. Med.34011691175CrossRefPubMedGoogle Scholar
  19. 19.
    Abernethy, LJ, Davidson, DC, Lamont, GL,  et al. 1998Intra-arterial calcium stimulation test in the investigation of hyperinsulinaemic hypoglycaemiaArch. Dis. Child.78359363PubMedGoogle Scholar
  20. 20.
    Doppman, JL, Chang, R, Fraker, DL,  et al. 1995Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calciumAnn. Intern. Med.12326927321PubMedGoogle Scholar
  21. 21.
    Harness, JK, Geelhoed, GW, Thompson, NW,  et al. 1981Nesidioblastosis in adults: a surgical dilemmaArch. Surg.116575580PubMedGoogle Scholar
  22. 22.
    Fong, TL, Warner, NE, Kumar, D 1989Pancreatic nesidioblastosis in adultsDiabetes Care12108114PubMedGoogle Scholar
  23. 23.
    McHenry, C, Newell, K, Chejfec, G,  et al. 1989Adult nesidioblastosis: an unusual cause of fasting hypoglycemiaAm. Surg.55366369PubMedGoogle Scholar
  24. 24.
    Witteles, RM, Straus, IF, Sugg, SL,  et al. 2001Adult-onset nesidioblastosis causing hypoglycemia: an important clinical entity and continuing treatment dilemmaArch. Surg.136656663CrossRefPubMedGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2004

Authors and Affiliations

  1. 1.Department of Surgery, Division of General Surgery, Section of Endocrine SurgeryUniversity of Vienna Medical SchoolViennaAustria

Personalised recommendations