• Kimberly Vanderveen
  • Clive Grant
Part of the Cancer Treatment and Research book series (CTAR, volume 153)


Insulinoma remains a very rare tumor, and the first challenge to making the diagnosis is to consider it. Although these tumors are typically benign, they can cause severe and often bizarre symptoms. The diagnosis is established with biochemical confirmation of hypoglycemia and endogenous hyperinsulinemia after fasting, and is distinguished from the postprandial hyperinsulinemic hypoglycemia of Noninsulinoma Pancreatogenous Hyperinsulinemia Syndrome (NIPHS). Operative removal of the tumor is the mainstay of treatment, but is predicated on precise preoperative localization. Multiple imaging options are available, including: transabdominal ultrasound, computed tomography, endoscopic ultrasound (EUS), angiography with intraarterial calcium stimulation testing, and intraoperative ultrasound (IOUS). Patients with MEN-1 syndrome virtually always have multiple pancreatic neuroendocrine tumors, and evaluation and treatment of these patients is different than for sporadic disease. Surgical excision of the disease is the only cure; in the rare case of malignant disease, an aggressive surgical and multimodal approach is recommended, even for palliation of hypoglycemia.


Distal Pancreatectomy Islet Cell Neoplasm Transabdominal Ultrasound Hyperinsulinemic Hypoglycemia Postprandial Hypoglycemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    van Heerden JA, Churchward MM (1999) Dr. Dickinson Ober Wheelock – a case of sporadic insulinoma or multiple endocrine neoplasia type 1? Mayo Clinic Proc 74:735–738Google Scholar
  2. 2.
    Wilder RM, Allan FN, Power MH et al (1927) Carcinoma of the islets of the pancreas: hyperinsulinism and hypoglycemia. JAMA 89:348Google Scholar
  3. 3.
    Morrison H (1937) Contributions to the microscopic anatomy of the pancreas by Paul Langerhans [Berlin, 1869]. [Translated from German]. Bull Hist Med 5:259–267Google Scholar
  4. 4.
    Banting FG (1937) Early work on insulin. Science 85:594–596CrossRefPubMedGoogle Scholar
  5. 5.
    Howland G, Campbell CW, Maltby EJ et al (1929) Dysinsulinism: convulsions and coma due to islet cell tumor of the pancreas with operation and cure. JAMA 93:674Google Scholar
  6. 6.
    Whipple AO, Frantz VK (1935) Adenoma of Islet cells with Hyperinsulinism: a review. Ann Surg 101:1299–1335CrossRefPubMedGoogle Scholar
  7. 7.
    Starr JI, Rubenstein AH (1974) Metabolism of endogenous proinsulin and insulin in man. J Clin Endocrinol Metab 38:305–308CrossRefPubMedGoogle Scholar
  8. 8.
    Service FJ (1995) Hypoglycemic disorders. N Engl J Med 332:1144–1152CrossRefPubMedGoogle Scholar
  9. 9.
    Service FJ, McMahon MM, O’Brien PC, Ballard DJ (1991) Functioning insulinoma–incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc 66:711–719PubMedGoogle Scholar
  10. 10.
    Doherty GM (2005) Multiple endocrine neoplasia type 1. J Surg Oncol 89:143–150CrossRefPubMedGoogle Scholar
  11. 11.
    Larsson C, Skogseid B, Oberg K et al (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85–87CrossRefPubMedGoogle Scholar
  12. 12.
    Doherty GM, Thompson NW (2003) Multiple endocrine neoplasia type 1: duodenopancreatic tumours. J Inst Med 253:590–598CrossRefGoogle Scholar
  13. 13.
    O’Brien T, O’Brien PC, Service FJ (1993) Insulin surrogates in insulinoma. J Clin Endocrinol Metab 77:448–451CrossRefPubMedGoogle Scholar
  14. 14.
    Pasieka JL, McLeod MK, Thompson NW, Burney RE (1992) Surgical approach to insulinomas. Assessing the need for preoperative localization. Arch Surg 127:442–447PubMedGoogle Scholar
  15. 15.
    Finlayson E, Clark OH (2004) Surgical treatment of insulinomas. Surg Clin North Am 84:775–785CrossRefPubMedGoogle Scholar
  16. 16.
    Service GJ, Thompson GB, Service FJ et al (2005) Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med 353:249–254CrossRefPubMedGoogle Scholar
  17. 17.
    Slooter GD, Mearadji A, Breeman WA et al (2001) Somatostatin receptor imaging, therapy and new strategies in patients with neuroendocrine tumours. Br J Surg 88:31–40CrossRefPubMedGoogle Scholar
  18. 18.
    Assalia A, Gagner M (2004) Laparoscopic pancreatic surgery for islet cell tumors of the pancreas. World J Surg 28:1239–1247CrossRefPubMedGoogle Scholar
  19. 19.
    Pierce RA, Spitler JA, Hawkins WG et al (2007) Outcomes analysis of laparoscopic resection of pancreatic neoplasms. Surg Endosc 21:579–586CrossRefPubMedGoogle Scholar
  20. 20.
    Menegaux F, Schmitt G, Mercadier M, Chigot JP (1993) Pancreatic insulinomas. Am J Surg 165:243–248CrossRefPubMedGoogle Scholar
  21. 21.
    Doherty GM, Doppman JL, Shawker TH et al (1991) Results of a prospective strategy to diagnose, localize, and resect insulinomas. Surgery 110:989–996PubMedGoogle Scholar
  22. 22.
    Phan GQ, Yeo CJ, Hruban RH et al (1998) Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients. J Gastrointest Surg 2:472–482CrossRefPubMedGoogle Scholar
  23. 23.
    Hirshberg B, Cochran C, Skarulis MC et al (2005) Malignant insulinoma: spectrum of unusual clinical features. Cancer 104:264–272CrossRefPubMedGoogle Scholar
  24. 24.
    Sarmiento JM, Que FG, Grand CS et al (2002) Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: outcomes of an aggressive approach. Surgery 132:976–982CrossRefPubMedGoogle Scholar
  25. 25.
    Siperstein AE, Berber E (2001) Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg 25:693–696CrossRefPubMedGoogle Scholar
  26. 26.
    Starke A, Saddig C, Mansfeld L et al (2005) Malignant metastatic insulinoma-postoperative treatment and follow-up. World J Surg 29:789–793CrossRefPubMedGoogle Scholar
  27. 27.
    Moertel CG, Lefkopoulo M, Lipsitz S et al (1992) Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 326:519–523CrossRefPubMedGoogle Scholar
  28. 28.
    Goode PN, Farndon JR, Anderson J et al (1986) Diazoxide in the management of patients with insulinoma. World J Surg 10:586–592CrossRefPubMedGoogle Scholar
  29. 29.
    Wicki A, Wild D, Storch D et al (2007) [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 is a highly efficient radiotherapeutic for glucagon-like peptide-1 receptor-targeted therapy for insulinoma. Clin Cancer Res 13:3696–3705CrossRefPubMedGoogle Scholar
  30. 30.
    Gagner M, Pomp A, Herrera MF (1996) Early experience with laparoscopic resections of islet cell tumors. Surgery 120:1051–1054CrossRefPubMedGoogle Scholar
  31. 31.
    Mabrut JY, Fernandez-Cruz L, Azagra JS et al (2005) Laparoscopic pancreatic resection: results of a multicenter European study of 127 patients. Surgery 137:597–605CrossRefPubMedGoogle Scholar
  32. 32.
    Kaczirek K, Asari R, Scheuba C, Niederle B (2005) Organic hyperinsulinism and endoscopic surgery. Wien Klin Wochenschrt 117:19–25CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of SurgeryMayo ClinicRochesterUSA

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