Skip to main content

Advertisement

SpringerLink
Log in

Insulinoma After Bariatric Surgery: Diagnostic Dilemma and Therapeutic Approaches

  • Review Article
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Hypoglycemia is increasingly recognized as a complication of bariatric surgery. Typically, hypoglycemia does not appear immediately postoperatively, but rather more than 1 year later, and usually occurs 1–3 h after meals. While rare, insulinoma has been reported after bariatric surgery. Clinical factors which should raise suspicion for insulinoma and the need for comprehensive clinical and biochemical evaluation include hypoglycemia occurring in the fasting state, predating bariatric surgery, and/or worsening immediately postoperatively, and lack of response to conservative therapy. Localization and successful resection of insulinoma can be achieved using novel endoscopic ultrasound and surgical approaches. In summary, hypoglycemia presenting shortly after gastric bypass or with a dominant fasting pattern should be fully evaluated to exclude insulinoma. Additionally, evaluation prior to gastric bypass should include screening for history of hypoglycemia symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Patti ME, Goldfine AB. Hypoglycemia after gastric bypass: the dark side of GLP-1. Gastroenterology. 2014;146(3):605–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Papamargaritis D et al. Dumping symptoms and incidence of hypoglycaemia after provocation test at 6 and 12 months after laparoscopic sleeve gastrectomy. Obes Surg. 2012;22(10):1600–6.

    Article  PubMed  Google Scholar 

  3. Calabria AC et al. Postoperative surveillance and detection of postprandial hypoglycemia after fundoplasty in children. J Pediatr. 2011;159(4):597–601. e1.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goldfine AB et al. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab. 2007;92(12):4678–85.

    Article  CAS  PubMed  Google Scholar 

  5. Salehi M, Prigeon RL, D’Alessio DA. Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans. Diabetes. 2011;60(9):2308–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jorgensen NB et al. Exaggerated glucagon-like peptide 1 response is important for improved beta-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes. 2013;62(9):3044–52.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Patti ME, Li P, Goldfine AB. Insulin response to oral stimuli and glucose effectiveness increased in neuroglycopenia following gastric bypass. Obesity (Silver Spring). 2015;23(4):798–807.

    Article  CAS  Google Scholar 

  8. Patti, M.E., et al., Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver.Spring.), 2009.

  9. Laferrere B et al. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011;3(80):80re2.

    PubMed  PubMed Central  Google Scholar 

  10. Hansen CF et al. Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats. PLoS ONE. 2013;8(6):e65696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liou AP et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra41.

    PubMed  PubMed Central  Google Scholar 

  12. Korner J et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786–95.

    Article  CAS  Google Scholar 

  13. Abood GJ et al. Robotic-assisted minimally invasive central pancreatectomy: technique and outcomes. J Gastrointest Surg. 2013;17(5):1002–8.

    Article  PubMed  Google Scholar 

  14. Meier JJ et al. Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased {beta}-cell turnover. Diabetes Care. 2006;29(7):1554–9.

    Article  PubMed  Google Scholar 

  15. Placzkowski KA et al. Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987–2007. J Clin Endocrinol Metab. 2009;94(4):1069–73.

    Article  CAS  PubMed  Google Scholar 

  16. Birkmeyer NJ, Gu N. Race, socioeconomic status, and the use of bariatric surgery in Michigan. Obes Surg. 2012;22(2):259–65.

    Article  PubMed  Google Scholar 

  17. Cryer PE et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709–28.

    Article  CAS  PubMed  Google Scholar 

  18. Iglesias P et al. Insulinoma-induced hypoglycemia in a patient with nesidiodysplasia after vagomotomy and pyloroplasty for duodenal ulcer. Am J Med Sci. 2009;337(5):377–80.

    Article  PubMed  Google Scholar 

  19. Seshadri P et al. Rare case of insulinoma diagnosed after laparoscopic gastric banding. Surg Obes Relat Dis. 2009;5(1):123–7.

    Article  PubMed  Google Scholar 

  20. Edis AJ et al. Insulinoma—current diagnosis and surgical management. Curr Probl Surg. 1976;13(10):1–45.

    Article  CAS  PubMed  Google Scholar 

  21. Karmali S et al. Weight recidivism post-bariatric surgery: a systematic review. Obes Surg. 2013;23(11):1922–33.

    Article  PubMed  Google Scholar 

  22. Saeidi N et al. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science. 2013;341(6144):406–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Drucker DJ et al. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci U S A. 1996;93(15):7911–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Goh BK et al. Accurate preoperative localization of insulinomas avoids the need for blind resection and reoperation: analysis of a single institution experience with 17 surgically treated tumors over 19 years. J Gastrointest Surg. 2009;13(6):1071–7.

    Article  PubMed  Google Scholar 

  25. Nikfarjam M et al. Improved contemporary surgical management of insulinomas: a 25-year experience at the Massachusetts General Hospital. Ann Surg. 2008;247(1):165–72.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gouya H et al. CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol. 2003;181(4):987–92.

    Article  PubMed  Google Scholar 

  27. Vaidakis D et al. Pancreatic insulinoma: current issues and trends. Hepatobiliary Pancreat Dis Int. 2010;9(3):234–41.

    PubMed  Google Scholar 

  28. Liu Y et al. The value of multidetector-row CT in the preoperative detection of pancreatic insulinomas. Radiol Med. 2009;114(8):1232–8.

    Article  CAS  PubMed  Google Scholar 

  29. McAuley G et al. Multimodality preoperative imaging of pancreatic insulinomas. Clin Radiol. 2005;60(10):1039–50.

    Article  CAS  PubMed  Google Scholar 

  30. Hirshberg B et al. Blind distal pancreatectomy for occult insulinoma, an inadvisable procedure. J Am Coll Surg. 2002;194(6):761–4.

    Article  PubMed  Google Scholar 

  31. Wilson JA et al. EUS in patients with surgically altered upper GI anatomy. Gastrointest Endosc. 2010;72(5):947–53.

    Article  PubMed  Google Scholar 

  32. Saftoiu A, Dietrich CF, Vilmann P. Contrast-enhanced harmonic endoscopic ultrasound. Endoscopy. 2012;44(6):612–7.

    Article  CAS  PubMed  Google Scholar 

  33. Hu M et al. Laparoscopic versus open treatment for benign pancreatic insulinomas: an analysis of 89 cases. Surg Endosc. 2011;25(12):3831–7.

    Article  PubMed  Google Scholar 

  34. Daouadi M et al. Robot-assisted minimally invasive distal pancreatectomy is superior to the laparoscopic technique. Ann Surg. 2013;257(1):128–32.

    Article  PubMed  Google Scholar 

  35. Antonakis PT, Ashrafian H, Martinez-Isla A. Pancreatic insulinomas: laparoscopic management. World J Gastrointest Endosc. 2015;7(16):1197–207.

    PubMed  PubMed Central  Google Scholar 

  36. Newman NA et al. Preoperative endoscopic tattooing of pancreatic body and tail lesions decreases operative time for laparoscopic distal pancreatectomy. Surgery. 2010;148(2):371–7.

    Article  PubMed  Google Scholar 

  37. Ayav A et al. Laparoscopic approach for solitary insulinoma: a multicentre study. Langenbecks Arch Surg. 2005;390(2):134–40.

    Article  CAS  PubMed  Google Scholar 

  38. Roslin MS et al. Response to glucose tolerance testing and solid high carbohydrate challenge: comparison between Roux-en-Y gastric bypass, vertical sleeve gastrectomy, and duodenal switch. Surg Endosc. 2014;28(1):91–9.

    Article  PubMed  Google Scholar 

  39. Xu G et al. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes. 1999;48(12):2270–6.

    Article  CAS  PubMed  Google Scholar 

  40. Reubi JC et al. Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass. Diabetologia. 2010;53(12):2641–5.

    Article  CAS  PubMed  Google Scholar 

  41. Service FJ et al. Functioning insulinoma—incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc. 1991;66(7):711–9.

    Article  CAS  PubMed  Google Scholar 

  42. Ponce J et al. American Society for Metabolic and Bariatric Surgery estimation of bariatric surgery procedures in the United States, 2011–2014. Surg Obes Relat Dis. 2015;11(6):1199–200.

    Article  PubMed  Google Scholar 

  43. Zagury L et al. Insulinoma misdiagnosed as dumping syndrome after bariatric surgery. Obes Surg. 2004;14(1):120–3.

    Article  PubMed  Google Scholar 

  44. Service GJ et al. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med. 2005;353(3):249–54.

    Article  CAS  PubMed  Google Scholar 

  45. Abellan P et al. Severe hypoglycemia after gastric bypass surgery for morbid obesity. Diabetes Res Clin Pract. 2008;79(1):e7–9.

    Article  PubMed  Google Scholar 

  46. Sato T et al. A case of insulinoma following total gastrectomy—effects of an alpha-glucosidase inhibitor on suppressing GIP and GLP-1 elevations. Diabetes Res Clin Pract. 2010;88(1):e4–6.

    Article  PubMed  Google Scholar 

  47. Guimaraes M et al. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass. Endocrinol Diabetes Metab Case Rep. 2015;2015:150049.

    PubMed  PubMed Central  Google Scholar 

  48. Koca YS et al. Insulinoma-induced hypoglycemia in a patient with insulinoma after gastrojejunostomy for prepyloric ulcer. Case Rep Surg. 2015;2015:127914.

    PubMed  PubMed Central  Google Scholar 

  49. Otonkoski T et al. Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes. 2003;52(1):199–204.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge grant support from NIH T32 DK007260 (to CMM) and NIH P30 DK036836 (Diabetes Research Center, Joslin).

Author information

Author notes

    Authors and Affiliations

    1. Research Division, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA

      Christopher M. Mulla & Mary-Elizabeth Patti

    2. Clinic Division, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA

      Christopher M. Mulla & Mary-Elizabeth Patti

    3. Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

      Christopher M. Mulla & Mary-Elizabeth Patti

    4. Harvard Medical School, Boston, MA, USA

      Christopher M. Mulla, Alessandra Storino, Eric U. Yee, David Lautz, Mandeep S. Sawnhey, A. James Moser & Mary-Elizabeth Patti

    5. Pancreas and Liver Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA

      Alessandra Storino & A. James Moser

    6. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

      Alessandra Storino & A. James Moser

    7. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA

      Eric U. Yee

    8. Department of Surgery, Emerson Hospital and Massachusetts General Hospital, Concord, MA, USA

      David Lautz

    9. Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

      Mandeep S. Sawnhey

    Authors
    1. Christopher M. Mulla
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Alessandra Storino
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Eric U. Yee
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. David Lautz
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Mandeep S. Sawnhey
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. A. James Moser
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Mary-Elizabeth Patti
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Mary-Elizabeth Patti.

    Ethics declarations

    Conflict of Interest

    Authors CMM, AS, EUY, DL, MSS, and AJM declare no conflict of interest. MEP reports grants from American Society for Metabolic and Bariatric Surgery, Medimmune, Nuclea Biosciences, Bristol-Myers Squibb, Astra-Zeneca, Novo-Nordisk Foundation, and Sanofi outside the submitted work. In addition, Dr. Patti has a submitted patent “Methods and Compositions for Treating Hypoglycemia.”

    Ethical Approval

    This review article does not contain any studies with human participants or animals performed by any of the authors.

    Informed Consent

    Does not apply to this review article.

    Additional information

    Christopher M. Mulla and Alessandra Storino contributed equally to this work.

    Electronic Supplementary Material

    Below is the link to the electronic supplementary material.

    ESM 1

    (DOCX 28 kb)

    ESM 2

    (DOCX 28 kb)

    ESM 3

    (DOCX 22 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Mulla, C.M., Storino, A., Yee, E.U. et al. Insulinoma After Bariatric Surgery: Diagnostic Dilemma and Therapeutic Approaches. OBES SURG 26, 874–881 (2016). https://doi.org/10.1007/s11695-016-2092-5

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11695-016-2092-5

    Keywords

    Search

    Navigation