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Hypercalcemia and pancreatic endocrine neoplasia with elevated PTH-rP: Report of two new cases and subject review

Journal of Gastrointestinal Surgery volume 9, pages 270–279 (2005)Cite this article

Abstract

Humoral hypercalcemia of malignancy is widely associated with tumor production of parathyroid hormone related protein (PTH-rP). This peptide functions in endocrine, autocrine and paracrine mechanisms in a manner similar to PTH; increasing renal uptake of calcium, decreasing retention of phosphorous, and stimulating adenylate cyclase and phospholipase C. Although PTH-rP production has been well documented in neoplasms of the exocrine pancreas, we present here two cases of endocrine pancreatic neoplasms elaborating PTH-rP. We then review the literature of previous cases and delve into the pathophysiology of this peptide.

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References

  1. Clemens TL, Cormier S, Eichinger A, et al. Parathyroid hormone-related protein and its receptors: Nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets. Br J Pharmacol 2001; 134:113–116.

    Article  Google Scholar 

  2. Asa SL, Henderson J, Goltzman D, Drucker DJ. Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues. J Clin Endocrinol Metab 1990;71:1112–1118.

    PubMed  CAS  Google Scholar 

  3. Juppner H, Abou-Samra AD, et al. The parathyroid hormonelike peptide associated with humoral hypercalcemia of malignancy and parathyroid hormone bind to the same receptor of the plasma membrane of ROS 17/2.8 cells. J Biol Chem 1988;263:8557–8560.

    PubMed  CAS  Google Scholar 

  4. Abou-Samra AB, Juppner H, Force T, et al. Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: A single receptor stimulates intracellular accumulation of both camp and inositol triphosphates and increases intracellular free calcium. Proc Natl Acad SciUSA 1992;9:2732–2736.

    Article  Google Scholar 

  5. Mao D, Carter P, Schaefer P, et al. Malignant islet cell tumor associated with hypercalcemia. Surgery 1995;117:37–40.

    PubMed  Article  CAS  Google Scholar 

  6. Ratcliffe WA, Bowden SJ, Dunne FP, et al. Expression and processing of parathyroid hormone-related protein in a pancreatic endocrine cell tumour associated with hypercalcemia. Clin Endocrinol 1994;40:679–686.

    CAS  Google Scholar 

  7. Miraliakbari BA, Asa SL, Boudreau SF. Parathyroid hormonelike peptide in pancreatic endocrine carcinoma and adenocarcinoma associated with hypercalcemia. Hum Pathol 1992; 23:884–887.

    PubMed  Article  CAS  Google Scholar 

  8. Drucker DJ, Asa SL, Henderson J, Goltzman D. The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas. Mol Endocrinol 1989;3:1589–1595.

    PubMed  CAS  Google Scholar 

  9. Karaplis AC, et al. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 1994;8:277–289.

    PubMed  Article  CAS  Google Scholar 

  10. Lanske B, Karapalis AC, Lee K, et al. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science 1996;273:663–666.

    PubMed  Article  CAS  Google Scholar 

  11. Vasavada RC, Garcia-Ocana A, Massfelder T, Dann P, Stewart AF. Parathyroid hormone-related protein in the pancreatic islet and the cardiovascular system. Recent Prog Horm Res 1998;53:305–338.

    PubMed  CAS  Google Scholar 

  12. Deftos IJ, Gazdar AF, Ikeda K, Broadnus AE. The parathyroid hormone-related protein associated with malignancy is secreted by neuroendocrine tumors. Mol Endocrinol 1989;3:503–508.

    PubMed  CAS  Google Scholar 

  13. Villanueva-Penacarrillo ML, Cancelas J, et al. Parathyroid hormone-related peptide stimulates DNA synthesis and insulin secretion in pancreatic islets. J Endocrinol 1999;163:403–408.

    PubMed  Article  CAS  Google Scholar 

  14. Nichols GA, Nana AD, Nichols MA, DiPette DJ, Asimakis GK. Hypotension and cardiac stimulation due to parathyroic hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology 1989;125:834–841.

    Google Scholar 

  15. Centrella M, Canalis E, McCarthy TL, et al. Parathyroid hormone-related protein modulates the effect of transforming growth factor-beta on deoxyribonucleic acid and collagen synthesis in fetal rat bone cells. Endocrinology 1989;125:199–208.

    PubMed  CAS  Article  Google Scholar 

  16. Ratcliffe WA. Parathyroid hormone-related protein: A polyhormonal enigma. Equine Vet J 1997;29:174–176.

    PubMed  CAS  Article  Google Scholar 

  17. Nagata N, Kugai N, Maemura M, et al. Enhancement of cyclic adenosine monophosphate content in bone cells by the factor extracted from a pancreatic cancer associated with hypercalcemia. Metabolism 1986;35:529–534.

    PubMed  Article  CAS  Google Scholar 

  18. Bandyopadhyay P,Baksi S, BandyopadhyayD,PatelCU.Parathyroid hormone-related protein in pancreatic exocrine cancer associated with hypercalcemia. Int J Clin Pract 2003;57:140–142.

    PubMed  CAS  Google Scholar 

  19. Vair DB, Boudreau SF, Reid SL. Pancreatic islet-cell neoplasia, with secretion of a parathormone-like substance and hypercalcemia. Can J Surg 1987;30:108–110.

    PubMed  CAS  Google Scholar 

  20. Wynick D, Ratcliffe WA, Health DA, et al. Treatment of a malignant pancreatic endocrine tumour secreting parathyroid hormone related protein. BMJ 1990;300:1314–1316.

    PubMed  CAS  Article  Google Scholar 

  21. Mitlak BH, Hutchison JS, Kaufman SD, Nussbaum SR. Parathyroid hormone-related peptide mediates hypercalcemia in an islet cell tumor of the pancreas. Horm Metab Res 1991; 23:344–346.

    PubMed  CAS  Google Scholar 

  22. Williams EJ, Ratcliffe WA, Stavri GT, Stamatakis JD. Hypercalcemia secondary to secretion of parathyroid hormone related protein from a somatostatinoma of the pancreas. Ann Clin Biochem 1992;29:354–357.

    PubMed  Google Scholar 

  23. Abraham P, Ralston SH, Hewison M, Fraser WD, Bevan JS. Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour, with hypercalaemic crisis, pre-eclampsia, and renal failure. Postgrad Med J 2002;78:752–753.

    PubMed  Article  CAS  Google Scholar 

  24. Walls J, Ratcliffe WA, Howell A, Bundred NJ. Parathyroid hormone and parathyroid hormone-related protein in the investigation of hypercalcemia in two hospital populations. Clin Endocrinol 1994;41:407–413.

    CAS  Google Scholar 

  25. Kakizaki S, Ohya N, Yoshinaga T, et al. Undifferentiated pancreatic cancer associated with humoral hypercalcemia of malignancy. Jpn J Clin Oncol 1998;28:563–566.

    PubMed  Article  CAS  Google Scholar 

  26. Birkeland KI, Gallefoss F, Olsson S, Haug E. Primary hyperparathyroidism or hypercalcemia of malignancy? Scand J Clin Lab Invest 1992;52:347–349.

    PubMed  CAS  Google Scholar 

  27. Tachibana I, Nakano S, Akiyama T, et al. Parathyroid hormone-related protein mediates hypercalcemia in an exocrine pancreatic cancer. Am J Gastroenterol 1994;89:1580–1581.

    PubMed  CAS  Google Scholar 

  28. YamamotoM, Nakano S, MugikuraM, et al. Pancreatic cancer and hypercalcemia associated with von Recklinghausen’s disease. J Gastroenterol 1996;1:728–731.

    Article  Google Scholar 

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Authors and Affiliations

  1. Departments of Surgery, Johns Hopkins Hospital, Halsted 610, 600 North Wolfe Street, 21287, Baltimore, Maryland

    Susanna L. Matsen M.D., Charles J. Yeo M.D. & Michael A. Choti M.D.

  2. Departments of Pathology, Johns Hopkins Hospital, Baltimore, Maryland

    Ralph H. Hruban M.D.

Authors
  1. Susanna L. Matsen M.D.
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  2. Charles J. Yeo M.D.
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  3. Ralph H. Hruban M.D.
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  4. Michael A. Choti M.D.
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Matsen, S.L., Yeo, C.J., Hruban, R.H. et al. Hypercalcemia and pancreatic endocrine neoplasia with elevated PTH-rP: Report of two new cases and subject review. J Gastrointest Surg 9, 270–279 (2005). https://doi.org/10.1016/j.gassur.2004.06.012

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Key Words

  • PTH-rP
  • pancreatic endocrine neoplasm
  • hypercalcemia