Skip to main content
Log in

Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay

  • Original Articles
  • Published:
The clinical investigator Aims and scope Submit manuscript

Summary

Overproduction of parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia of malignancy in patients with solid tumors. We measured plasma levels of the protein by a radioimmunoassay (RIA) against PTHrP(5384) and by an immunoradiometric assay (IRMA) against PTHrP(1–86). Of 16 affected patients 7 had elevated PTHrP levels in both assays and 4 had elevated levels in the RIA only. Median levels were about tenfold higher in these patients when measured by RIA (median of 34 versus 2.2 pmol/1). Measurements from both assays were, however, highly correlated with each other in this patient group (P<0.01). PTHrP was not elevated in 10 normocalcemic patients with lung carcinoma. During long-term follow-up of a patient with a mesothelioma of the pleura, PTHrP levels measured with both assays decreased during chemotherapy in parallel with a normalization of serum calcium. In another hypercalcemic patient suffering from renal carcinoma, PTHrP measured by IRMA decreased by 40% within 12 h after nephrectomy, whereas PTHrP measured by RIA did not show a significant decline. Direct comparison of the assay results thus pointed to the existence of heterogeneity of circulating forms of PTHrP in plasma. In conclusion, both immunoassays detected elevated levels of PTHrP in a fraction of patients with hypercalcemia of malignancy and thus may be a tumor marker during treatment of malignancies.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

PTHrP:

parathyroid hormone-related protein

PTH:

parathyroid hormone

RIA:

radioimmunoassay

IRMA:

immunoradiometric assay

References

  1. Bilezikian JP (1990) Parathyroid hormone-related peptide in sickness and in health (editorial). N Engl J Med 322:1151–1153

    Google Scholar 

  2. Bilezikian JP (1991) Measurement of parathyroid hormone-related peptide in the circulation. Trends Endocrinol Metab 2:1–3

    Google Scholar 

  3. Blind E (1991) Immunoassays für Parathyroid Hormone-Related Protein (PTHrP). Klin Lab 37:297–298

    Google Scholar 

  4. Blind E, Raue F, Götzmann J, Schmidt-Gayk H, Kohl B, Ziegler R (1992) Circulating levels of parathyroid hormone-related protein in hypercalcemia of malignancy. Clin Endocrinol 37:290–297

    Google Scholar 

  5. Blind E, Raue F, Meinel T, Wüster C, Ziegler R (1993) Levels of parathyroid hormone-related protein (PTHrP) in hypercalcemia of malignancy are not lowered by treatment with the bisphosphonate BM 21.0955. Horm Metab Res (in press)

  6. Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF (1988) Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med 319:556–563

    Google Scholar 

  7. Budayr AA, Nissenson RA, Klein RF, Pun KK, Clark OH, Diep D, Arnaud CD, Strewler GJ (1989) Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcemia. Ann Int Med 111: 807–812

    Google Scholar 

  8. Burtis WJ, Wu T, Bunch C, Wysolmerski JJ, Insogna KL, Weir EC, Broadus AE, Stewart AF (1987) Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem 262:7151–7156

    Google Scholar 

  9. Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RJ, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF (1990) Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med 322:1106–1112

    Google Scholar 

  10. Dodwell DJ, Abbas SK, Morton AR, Howell A (1991) Parathyroid hormone-related protein(50–69) and response to pamidronate therapy for tumour-induced hypercalcemia. Eur J Cancer 27:1629–1633

    Google Scholar 

  11. Grill V, Ho P, Body JJ, Johanson N, Lee SC, Kukreja SC, Moseley J, Martin TJ (1991) Parathyroid hormone related protein: elevated levels in both Immoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab 73:1309–1315

    Google Scholar 

  12. Henderson JE, Shustik C, Kremer R, Rabbani SA, Hendy GN, Goltzman D (1990) Circulating concentrations of parathyroid hormone-like peptide in malignancy and in hyper-parathyroidism. J Bone Miner Res 5:105–113

    Google Scholar 

  13. Jüppner H, Abou SA, Uneno S, Gu WX, Potts JT Jr, Segre GV (1988) The parathyroid hormone-like peptide associated with humoral hypercalcemia of malignancy and parathyroid hormone bind to the same receptor on the plasma membrane of ROS 17/2.8 cells. J Biol Chem 263:8557–8560

    Google Scholar 

  14. Kao PC, Klee GG, Taylor RL, Heath H III (1990) Parathyroid hormone-related peptide in plasma of patients with hypercalcemia and malignant lesions. Mayo Clin Proc 65:1399–1407

    Google Scholar 

  15. Mangin M, Webb AC, Dreyer BE, Posillico JT, Ikeda K, Weir EC, Stewart AF, Bander NH, Milstone L, Barton DE, Franke U, Broadus AE (1988) Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with Immoral hypercalcemia of malignancy. Proc Natl Acad Sci USA 85:597–601

    Google Scholar 

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

    Google Scholar 

  17. Moseley JM, Kubota M, Diefenbach JH, Wettenhall RE, Kemp BE, Suva LJ, Rodda CP, Ebeling PR, Hudson PJ, Zajac JD, Martin TJ (1987) Parathyroid hormone-related protein purified from a human lung cancer cell line. Proc Natl Acad Sci USA 84:5048–5052

    Google Scholar 

  18. Pandian MR, Morgan CH, Carlton E, Segre GV (1992) Modified immunoradiometric assay of parathyroid hormone-related protein: clinical application in the differential diagnosis of hypercalcemia. Clin Chem 38:282–288

    Google Scholar 

  19. Ratcliffe WA, Ratcliffe JG (1990) Parathyroid hormone-related protein. In: Schmidt-Gayk H, Armbruster FP, Bouillon R (eds) Calcium regulating hormones, vitamin D metabolites, and cyclic AMP assays and their clinical application. Springer, Berlin Heidelberg New York, pp 213–227

    Google Scholar 

  20. Ratcliffe WA, Norbury S, Heath DA, Ratcliffe JG (1991) Development and validation of an immunoradiometric assay of parathyrin-related protein in unextracted plasma. Clin Chem 37:678–685

    Google Scholar 

  21. Ratcliffe WA, Norbury S, Stott RA, Heath DA, Ratcliffe JG (1991) Immunoreactivity of plasma parathyrin-related peptide: three region-specific radioimmunoassays and a two-site immunoradiometric assay compared. Clin Chem 37:1781–1787

    Google Scholar 

  22. Ratcliffe WA, Hutchesson ACJ, Bundred NJ, Ratcliffe JG (1992) Role of assays for parathyroid-hormone-related protein in investigation of hypercalcemia. Lancet 339:164–167

    Google Scholar 

  23. Soifer NE, Stewart AF (1992) Measurement of PTH-related protein and the role of PTH-related protein in malignancy-associated hypercalcemia. In: Halloran BP, Nissenson RA (eds) Parathyroid hormone-related protein: normal physiology and its role in cancer. CRC press, Boca Raton, pp 93–143

    Google Scholar 

  24. Stewart AF, Broadus AE (1990) Clinical review 16: parathyroid hormone-related proteins: coming of age in the 1990s. J Clin Endocrinol Metab 71:1410–1414

    Google Scholar 

  25. Thiede MA, Strewler GJ, Nissenson RA, Rosenblatt M, Rodan GA (1988) Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene. Proc Natl Acad Sci USA 85:4605–4609

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blind, E., Raue, F., Meinel, T. et al. Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay. Clin Investig 71, 31–36 (1993). https://doi.org/10.1007/BF00210960

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00210960

Key words

Navigation