Advertisement

Endocrine Pathology

, Volume 29, Issue 1, pp 15–20 | Cite as

Pancreatic Neuroendocrine Tumor Producing Insulin and Vasopressin

  • Omalkhaire M. Alshaikh
  • Ju-Yoon Yoon
  • Bryan A. Chan
  • Monika K. Krzyzanowska
  • Jagdish Butany
  • Sylvia L. Asa
  • Shereen Ezzat
Article

Abstract

The objective of the study is to report a rare case of pancreatic neuroendocrine tumor (pNET) producing insulin and vasopressin. We describe the clinical presentation and management of a metastatic pNET with refractory hypoglycemia and progressive severe hyponatremia. A 52-year-old patient had abdominal pain leading to the diagnosis of a tumor that was initially presumed to be splenic in origin. Investigations ultimately identified a pancreatic mass that on biopsy proved to be a pNET. Eventually, he developed extensive liver metastases, and with tumor progression, he manifested hypoglycemia and severe hyponatremia. He was managed with multiple therapies including somatostatin analogue, peptide-receptor-radionuclide-therapy (PRRT), diazoxide, and everolimus; none of these therapeutic modalities was successful in controlling functional and structural progression of the tumor. Ultimately, the pNET proved fatal and autopsy confirmed widely metastatic disease that stained strongly and diffusely for vasopressin, a feature not seen in the previous liver biopsy. This case illustrates the challenges of diagnosis and management of aggressive insulin-producing pNETs and highlights the potential concomitant ectopic production of vasopressin leading to refractory hyponatremia.

Keywords

Pancreatic neuroendocrine tumors Neuroendocrine tumors Insulin Vasopressin 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    de Herder WW, Niederle B, Scoazec JY, Pauwels S, Kloppel G, Falconi M, et al. Well-differentiated pancreatic tumor/carcinoma: insulinoma. Neuroendocrinology. 2006;84(3):183–188.CrossRefPubMedGoogle Scholar
  2. 2.
    Castillo JJ, Vincent M, Justice E. Diagnosis and management of hyponatremia in cancer patients. Oncologist. 2012;17(6):756–765.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kunc M, Gabrych A, Czapiewski P, Sworczak K. Paraneoplastic syndromes in olfactory neuroblastoma. Contemp Oncol (Pozn). 2015;19(1):6–16.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Hwang K, Jeon D-H, Jang HN, Bae EJ, Lee JS, Cho HS, et al. Inappropriate antidiuretic hormone syndrome presenting as ectopic antidiuretic hormone-secreting gastric adenocarcinoma: a case report. Journal of Medical Case Reports. 2014;8:185.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yarmohammadi H, Erinjeri JP, Brown KT. Embolization of metastatic neuroendocrine tumor resulting in clinical manifestations of syndrome of inappropriate secretion of antidiuretic hormone. J Vasc Interv Radiol. 2015;26(4):533–537.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ezzat S. PANCREATIC INCIDENTALOMAS: IS IT NET OR NOT? Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2016;22(7):895–896.CrossRefGoogle Scholar
  7. 7.
    Shreenivas AV, Leung V. A Rare Case of Insulinoma Presenting with Postprandial Hypoglycemia. The American Journal of Case Reports. 2014;15:488–491.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Fadini GP, Maran A, Valerio A, Meduri F, Pelizzo M, Miotto D, et al. Hypoglycemic Syndrome in a Patient with Proinsulin-Only Secreting Pancreatic Adenoma (Proinsulinoma). Case Reports in Medicine. 2011;2011:1–5.CrossRefGoogle Scholar
  9. 9.
    Gomez-Perez FJ, Cuevas-Ramos D, Valdes PA, Aguilar-Salinas CA, Mehta R, Rull JA. Beta-cell adenomas without hyperinsulinemia with use of highly specific insulin radioimmunoassays: case report and review of literature. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2010;16(4):660–663.CrossRefGoogle Scholar
  10. 10.
    Carneiro DM, Levi JU, Irvin GL, 3rd Rapid insulin assay for intraoperative confirmation of complete resection of insulinomas. Surgery. 2002;132(6):937–942; discussion 42-3.CrossRefPubMedGoogle Scholar
  11. 11.
    Kamocki ZK, Wodynska NA, Pryczynicz A. Co-existence of insulinoma and diabetes: A case report. Oncol Lett 2014;8(4):1697–1700.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Melloul D, Marshak S, Cerasi E. Regulation of insulin gene transcription. Diabetologia 2002;45(3):309–326.CrossRefPubMedGoogle Scholar
  13. 13.
    Biondi CA, Gartside MG, Waring P, Loffler KA, Stark MS, Magnuson MA, et al. Conditional Inactivation of the Men1 Gene Leads to Pancreatic and Pituitary Tumorigenesis but Does Not Affect Normal Development of These Tissues. Molecular and Cellular Biology. 2004;24(8):3125–3131.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Balogh K, Rácz K, Patócs A, Hunyady L. Menin and its interacting proteins: elucidation of menin function. Trends in Endocrinology & Metabolism. 2006;17(9):357–364.CrossRefGoogle Scholar
  15. 15.
    Cao Y, Gao Z, Li L, Jiang X, Shan A, Cai J, et al. Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1. Nat Commun. 2013;4:2810.PubMedGoogle Scholar
  16. 16.
    Zhan HX, Cong L, Zhao YP, Zhang TP, Chen G, Zhou L, et al. Activated mTOR/P70S6K signaling pathway is involved in insulinoma tumorigenesis. J Surg Oncol. 2012;106(8):972–980.CrossRefPubMedGoogle Scholar
  17. 17.
    Taskin M, Barker B, Calanog A, Jormark S. Syndrome of inappropriate antidiuresis in ovarian serous carcinoma with neuroendocrine differentiation. Gynecologic Oncology. 1996;62(3):400–404.CrossRefPubMedGoogle Scholar
  18. 18.
    Pifano M, Garona J, Capobianco CS, Gonzalez N, Alonso DF, Ripoll GV. Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells. Front Oncol. 2017;7:11.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Louiset E, Contesse V, Groussin L, Cartier D, Duparc C, Perraudin V, et al. Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: molecular, immunohistochemical and pharmacological correlates. J Endocrinol. 2008;196(1):1–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Eliasson L, Esguerra J. Role of non-coding RNAs in pancreatic beta-cell development and physiology. Acta Physiologica. 2014;211(2):273–284.CrossRefPubMedGoogle Scholar
  21. 21.
    Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, et al. DAXX/ATRX/MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors. Science. 2011;331(6021):1199–1203.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med. 2006;119(7 Suppl 1):S36–S42.CrossRefPubMedGoogle Scholar
  23. 23.
    Sterns RH, Silver SM. Brain volume regulation in response to hypo-osmolality and its correction. Am J Med. 2006;119(7 Suppl 1):S12–S16.CrossRefPubMedGoogle Scholar
  24. 24.
    Cardenas A, Gines P, Marotta P, Czerwiec F, Oyuang J, Guevara M, et al. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. Journal of hepatology. 2012;56(3):571–578.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Omalkhaire M. Alshaikh
    • 1
    • 2
  • Ju-Yoon Yoon
    • 3
  • Bryan A. Chan
    • 2
  • Monika K. Krzyzanowska
    • 2
  • Jagdish Butany
    • 3
  • Sylvia L. Asa
    • 3
  • Shereen Ezzat
    • 2
  1. 1.Department of Internal MedicineAl Imam Mohammad Ibn Saud Islamic University (IMSIU)RiyadhSaudi Arabia
  2. 2.Department of Medicine, Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  3. 3.Department of Pathology, University Health NetworkUniversity of TorontoTorontoCanada

Personalised recommendations