Journal of General Internal Medicine

, Volume 28, Issue 11, pp 1525–1529

Putting the Pieces Together: Necrolytic Migratory Erythema and the Glucagonoma Syndrome

  • Stephanie A. C. Halvorson
  • Erin Gilbert
  • R. Samuel Hopkins
  • Helen Liu
  • Charles Lopez
  • Michael Chu
  • Marie Martin
  • Brett Sheppard
Clinical Practice: Clinical Vignettes


Glucagonomas are slow-growing, rare pancreatic neuroendocrine tumors. They may present with paraneoplastic phenomena known together as the “glucagonoma syndrome.” A hallmark sign of this syndrome is a rash known as necrolytic migratory erythema (NME). In this paper, the authors describe a patient with NME and other features of the glucagonoma syndrome. The diagnosis of this rare tumor requires an elevated serum glucagon level and imaging confirming a pancreatic tumor. Surgical and medical treatment options are reviewed. When detected early, a glucagonoma is surgically curable. It is therefore imperative that clinicians recognize the glucagonoma syndrome in order to make an accurate diagnosis and refer for treatment.


glucagonoma neuroendocrine tumors necrolytic migratory erythema 


  1. 1.
    Batcher E, Madaj P, Gianoukakis AG. Pancreatic neuroendocrine tumors. Endocr Res. 2011;36(1):35–43.PubMedCrossRefGoogle Scholar
  2. 2.
    Yao J, Eisner M, Leary C, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol. 2007;14(12):3492–500.PubMedCrossRefGoogle Scholar
  3. 3.
    Eldor R, Glaser B, Fraenkel M, Doviner V, Salmon A, Gross DJ. Glucagonoma and the glucagonoma syndrome – cumulative experience with an elusive endocrine tumour. Clin Endocrinol. 2011;74(5):593–8.CrossRefGoogle Scholar
  4. 4.
    Seregni E, Ferrari L, Bajetta E, Martinetti A, Bombardieri E. Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Oncol. 2001;12(suppl 2):S69–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Kindmark H, Sundin A, Granberg D, et al. Endocrine pancreatic tumors with glucagon hypersecretion: a retrospective study of 23 cases during 20 years. Med Oncol. 2007;24(3):330.PubMedCrossRefGoogle Scholar
  6. 6.
    Wermers R, Fatourechi V, Wynne A, Kvols L, Lloyd R. The glucagonoma syndrome. Clinical and pathologic features in 21 patients. Medicine. 1996;75:53–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Stacpoole PW. The glucagonoma syndrome: clinical features, diagnosis, and treatment. Endocr Rev. 1981;2(3):347–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Alexander EK, Robinson M, Staniec M, Dluhy RG. Peripheral amino acid and fatty acid infusion for the treatment of necrolytic migratory erythema in the glucagonoma syndrome. Clin Endocrinol. 2002;57(6):827–31.CrossRefGoogle Scholar
  9. 9.
    Chastain MA. The glucagonoma syndrome: a review of its features and discussion of new perspectives. Am J Med Sci. 2001;321(5):306–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Mullans EA, Cohen PR. Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. J Am Acad Dermatol. 1998;38(5, Supplement):866–73.PubMedCrossRefGoogle Scholar
  11. 11.
    van Beek AP, de Haas ERM, van Vloten WA, Lips CJM, Roijers JFM, Canninga-van Dijk MR. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Eur J Endocrinol. 2004;151:531–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Perry RR, Vinik AI. Clinical review 72: diagnosis and management of functioning islet cell tumors. J Clin Endocrinol Metab. 1995;80(8):2273–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lobo I, Carvalho A, Amaral C, Machado S, Carvalho R. Glucagonoma syndrome and necrolytic migratory erythema. Int J Dermatol. 2010;49(1):24–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Tierney EP, Badger J. Etiology and pathogenesis of necrolytic migratory erythema: review of the literature. Medscape General Medicine. September 10, 2004 ed. Volume 6, 2004.Google Scholar
  15. 15.
    Khandekar J, Oyer D, Miller H, Vick N. Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin. Cancer. 1979;44(6):2014–6.PubMedCrossRefGoogle Scholar
  16. 16.
    McGevna L, McFadden D, Ritvo J, Rabinowitz T. Glucagonoma-associated neuropsychiatric and affective symptoms: diagnostic dilemmas raised by paraneoplastic phenomena. Psychosomatics. 2009;50(5):548–9.PubMedGoogle Scholar
  17. 17.
    Holmes A, Kilpatrick C, Proietto J, Green MD. Reversal of a neurologic paraneoplastic syndrome with octreotide (sandostatin) in a patient with glucagonoma. Am J Med. 1991;91(4):434–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Akerstrom G, Hellman P. Surgical aspects of neuroendocrine tumours. Eur J Cancer. 2009;45(Suppl 1):237–50.PubMedCrossRefGoogle Scholar
  20. 20.
    Hill JS, McPhee JT, McDade TP, et al. Pancreatic neuroendocrine tumors. Cancer. 2009;115(4):741–51.PubMedCrossRefGoogle Scholar
  21. 21.
    FtAF F, Giovannini M, Monges G, et al. EUS-FNA predicts 5-year survival in pancreatic endocrine tumors. Gastrointest Endosc. 2009;70(5):907–14.CrossRefGoogle Scholar
  22. 22.
    Mansour JC, Chen H. Pancreatic endocrine tumors. J Surg Res. 2004;120(1):139–61.PubMedCrossRefGoogle Scholar
  23. 23.
    Sundin A, Garske U, Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract Res, Clin Endocrinol Metab. 2007;21(1):69–85.CrossRefGoogle Scholar
  24. 24.
    National Comprehensive Cancer Network (NCCN) guidelines. <>. Accessed March 14, 2013.
  25. 25.
    Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol. 1999;17(2):600.PubMedGoogle Scholar
  26. 26.
    Rinke A, Muller H-H, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol. 2009;27(28):4656–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Norton J, Kivlen M, Li M, Schneider D, Chuter T, Jensen RT. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg. 2003;138(8):859–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Kunz PL, Fisher GA. Advances in the treatment of gastroenteropancreatic neuroendocrine tumors. Clin Exp Gastroenterol. 2010;3:79–86.PubMedGoogle Scholar
  29. 29.
    Schmidt C, Bloomston M, Shah MH. Well-differentiated neuroendocrine tumors: a review covering basic principles to loco-regional and targeted therapies. Oncogene. 2011;30:1497–505.PubMedCrossRefGoogle Scholar
  30. 30.
    Raymond E, Dahan L, Raoul J-L, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501–13.PubMedCrossRefGoogle Scholar

Copyright information

© Society of General Internal Medicine 2013

Authors and Affiliations

  • Stephanie A. C. Halvorson
    • 1
  • Erin Gilbert
    • 2
  • R. Samuel Hopkins
    • 3
  • Helen Liu
    • 3
  • Charles Lopez
    • 4
  • Michael Chu
    • 5
  • Marie Martin
    • 6
  • Brett Sheppard
    • 2
  1. 1.Division of Hospital Medicine, Department of MedicineOregon Health & Science UniversityPortlandUSA
  2. 2.Department of SurgeryOregon Health & Science UniversityPortlandUSA
  3. 3.Department of DermatologyOregon Health & Science UniversityPortlandUSA
  4. 4.Knight Cancer InstituteOregon Health & Science UniversityPortlandUSA
  5. 5.Division of Endocrinology, Diabetes and Clinical Nutrition, Department of MedicineOregon Health & Science UniversityPortlandUSA
  6. 6.Oregon Health & Science UniversityPortlandUSA

Personalised recommendations