Epidemiological Aspects of Hypercalcemia of Malignancy

Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 137)


Hypercalcemia can be caused by many disorders, but is most commonly due to primary hyperparathyroidism and to malignant disease. Together, these account for more than 90% of all cases. Many patients with primary hyperparathyroidism are asymptomatic and ambulant when hypercalcemia is first recognized by routine measurement of serum calcium levels. However, the incidence of hypercalcemia of cancer, which has been estimated to be about 150 new cases per million persons per year, is not as high as the annual incidence rate of primary hyperparathyroidism (approximately 250 new cases per year) (Burkhardt and Kistler 1981; Heath et al. 1980; Mundy et al. 1980, 1984).


Multiple Myeloma Bone Metastasis Primary Hyperparathyroidism Epidemiological Aspect Humoral Hypercalcemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bender RA, Hansen H (1974) Hypercalcemia in bronchogenic carcinoma: a prospective study of 200 patients. Ann Intern Med 80:205–208PubMedGoogle Scholar
  2. Bertolini DR, Nedwin GE, Bringman TS, Mundy GR (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factor. Nature 319:515–518CrossRefGoogle Scholar
  3. Blind E, Raue F, Zisterer A, Kohl B, Ziegler R (1990) Epidemiologie der Hyper-calcämie, Bedeutung der Bestimmung des intakten Parathormons für die Differentialdiagnose. Dtsch Med Wochenschr 115:1739–1745PubMedCrossRefGoogle Scholar
  4. Blomqvist CP (1986) Malignant hypercalcemia: a hospital survey. Acta Med Scand 220:455–463PubMedCrossRefGoogle Scholar
  5. Breslau NA, McGuire JL, Zerwekh JE, Frenkel EP, Pak CYC (1984) Hypercalcemia associated with increased serum calcitriol levels in three patients with lymphoma. Ann Intern Med 100:1–7PubMedGoogle Scholar
  6. Buckman R, Cuzick J, Galton DAG (1982) Long term survival in myelomatosis: a report to the MRC working party on leukaemia in adults. Br J Haematol 52: 589–559PubMedCrossRefGoogle Scholar
  7. Bundred NJ, Ratcliffe WA, Walker RA, Coley S, Morrison JM, Ratcliffe JR (1991) Parathyroid hormone related protein and hypercalcemia in breast cancer. Br J Cancer 303:1506–1509Google Scholar
  8. Bundred NJ, Walker RA, Ratcliffe WA, Warwick J, Morrison JM, Ratcliffe JR (1992) Parathyroid hormone-related protein and skeletal morbidity in breast cancer. Eur J Cancer 28:690–692PubMedCrossRefGoogle Scholar
  9. Bunn PA, Schlechter GP, Jaffe E, Blayney D, Young RC, Matthew MJ, Blattner W, Broder S, Gadroff MR, Gallo RC (1983) Clinical course of retrovirus-associated adult T-cell lymphoma in the US. N Engl J Med 309:257–264PubMedCrossRefGoogle Scholar
  10. Burkhardt E, Kistler JJ (1981) Hypercalciämie bei hospitalisierten Patienten. Schweiz Med Wochenschr 111:2017–2023PubMedGoogle Scholar
  11. Burt ME, Brennan MF (1980) Incidence of hypercalcemia and malignant neoplasm. Arch Surg 115:704–707PubMedCrossRefGoogle Scholar
  12. Coggeshall J, Merrill W, Hande K, Prez RD (1986) Implications of hypercalcemia with respect to diagnosis and treatment of lung cancer. Am J Med 80:325–328PubMedCrossRefGoogle Scholar
  13. Coleman RE, Rubens RD (1985) Bone metastases and breast cancer. Cancer Treat Rev. 12:251–270PubMedCrossRefGoogle Scholar
  14. Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66PubMedCrossRefGoogle Scholar
  15. Coleman RL, Fogelman I, Rubens RD (1988) Hypercalcemia and breast cancer: an increased humoral component in patients with liver metastases. Eur J Surg Oncol 14:428–443Google Scholar
  16. Durie BGM, Salmon SE (1982) Current status and future prospects for treatment in multiple myeloma. Clin Haematol 11:181–210PubMedGoogle Scholar
  17. Elomaa I, Blomquist C, Grohn P, Porkka L, Kairento AL, Seiander K, Lamberg-Allardt G, Holmstrom T (1983) Long-term controlled trial with diphosphonate in patients with osteologic bone metastases. Lancet i:146–148CrossRefGoogle Scholar
  18. Fahn HJ, Lee YH, Chen MT, Huang JK, Chen KK, Chang LS (1991) The incidence and prognostic significance of humoral hypercalcemia in renal cell carcinoma. J Urol 145:248–250PubMedGoogle Scholar
  19. Fisken RA, Heath DA, Bold AM (1980) Hypercalcemia — a hospital survey. Q J Med 49:405–418PubMedGoogle Scholar
  20. Fisken RA, Heath DA, Somers S (1981) Hypercalcemia in hospital patients: clinical and diagnostic aspects. Lancet i:202–207CrossRefGoogle Scholar
  21. Galasko CSB, Burn JL (1971) Hypercalcemia in patients with advanced mammary cancer. Br Med J 3:573–577PubMedCrossRefGoogle Scholar
  22. Gowen M, Wood OD, Ihrie EJ, McGuire MKB, Russell RGG (1983) An interleukin 1 like factor stimulates bone resorption in vitro. Nature 306:376–380CrossRefGoogle Scholar
  23. Grossmann B, Schechter GP, Horton JE, Pierce L, Juffe E, Wahl L (1981) Hypercalcemia associated with T-cell lymphoma-leukemia. Am J Clin Pathol 75: 149–155Google Scholar
  24. Heath H III, Hodgson SF, Kennedy MA (1980) Primary hyperparathyroidism: incidence, morbidity, and potential economic impact in a community. N Engl J Med 302:189–193PubMedCrossRefGoogle Scholar
  25. Hickey RC, Samaan NA, Jackson GL (1981) Hypercalcemia in patients with breast cancer. Arch Surg 116:545–552PubMedGoogle Scholar
  26. Isales C, Carangiu ML, Stewart AF (1987) Hypercalcemia in breast cancer: reassessment of the mechanism. Am J Med 82:1142–1147CrossRefGoogle Scholar
  27. Kyle RA (1985) Multiple myeloma: current therapy and a glimpse of the future. Scand J Haematol 35:38–47PubMedCrossRefGoogle Scholar
  28. Legha SS, Powell K, Buzdar AU, Blumenschein GR (1981) Tamoxifen-induced hypercalcemia in breast cancer. Cancer 47:2803–2806PubMedCrossRefGoogle Scholar
  29. McCanley LK, Rosol TJ, Merryman JI, Capen CC (1992) Parathyroid hormone-related protein binding to human T-cell lymphotropic virus type I-infected lymphocytes. Endocrinology 130:300–306CrossRefGoogle Scholar
  30. Muggia FM (1990) Overview of cancer-related hypercalcemia: epidemiology and etiology. Semin Oncol 17[Suppl 5]:3–9PubMedGoogle Scholar
  31. Mundy GR (1988) Hypercalcemia of malignancy revisited. J Clin Invest 82:1–6PubMedCrossRefGoogle Scholar
  32. Mundy GR (1990) Pathophysiology of cancer-associated hypercalcemia. Semin Oncol 17[Suppl 5]: 10–15PubMedGoogle Scholar
  33. Mundy GR, Martin TJ (1982) The hypercalcemia of malignancy: pathogenesis and management. Metabolism 31:1247–1277PubMedCrossRefGoogle Scholar
  34. Mundy GR, Cove DH, Fisken R (1980) Primary hyperparathyroidism: changes in the pattern of clinical presentation. Lancet i: 1317–1320CrossRefGoogle Scholar
  35. Mundy GR, Ibbotson KJ, D’Souza SM, Simpson EL, Jacobs JW, Martin TJ (1984) The hypercalcemia of cancer: clinical implications and pathologic mechanisms. N Engl J Med 310:1718–1727PubMedCrossRefGoogle Scholar
  36. Myers WPL (1973) Hypercalcemia associated with maligant diseases. In: Schwartz TB (ed) Endocrine and nonendocrine hormone-producing tumors. Year Book Medical Publishers, Chicago, pp 147–171Google Scholar
  37. Otteman LA, Long HJ (1984) Hypercalcemic flare with megestol acetate. Cancer Treat Rep 68:1420–1421PubMedGoogle Scholar
  38. Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, Bennett RC, Martin TJ (1991) Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 51:3059–3061PubMedGoogle Scholar
  39. Ralston SH, Gallagher SJ, Patel U, Campbell J, Boyle IT (1990) Cancer-associated hypercalcemia: morbidity and mortality clinical experience in 126 treated patients. Ann Intern Med 112:499–504PubMedGoogle Scholar
  40. Rosol TJ, Capen CC (1992) Biology of disease: mechanisms of cancer-induced hypercalcemia. Lab Invest 67:680–702PubMedGoogle Scholar
  41. Scheid V, Buzdar AU, Smith TL, Hortobagyi GN (1986) Clinical course of breast cancer patients with osseous metastases treated with combination chemotherapy. Cancer 58:2589–2593PubMedCrossRefGoogle Scholar
  42. Sklaroff DM, Charker ND (1968) Bone metastases from breast cancer at the time of the radical mastectomy. Surg Gynecol Obstet 127:763–768PubMedGoogle Scholar
  43. Skrabanek P, McPartlin M, Powell D (1980) Tumor hypercalcemia and “ectopic hyperparathyroidism”. Medicine 59:262–282PubMedCrossRefGoogle Scholar
  44. Stewart AF, Mangin M, Wu T, Goumas D, Insogna KL, Burtis WJ, Broadus AE (1988) Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats. J Clin Invest 81:596–600PubMedCrossRefGoogle Scholar
  45. Vassilopoulou-Sellin R, Newman BM, Taylor SH, Guinee VF (1993) Incidence of hypercalcemia in patients with malignancy referred to a comprehensive cancer center. Cancer 71:1309–1312PubMedCrossRefGoogle Scholar
  46. Warrell RP, Israel R, Frisone M, Snyder T, Gaynor JJ, Bockman RS (1988) Gallium nitrate for acute treatment of cancer-related hypercalcemia: a randomized, double-lind comparison to calcitonin. Ann Intern Med 108:669–674PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • F. Raue
    • 1
  1. 1.Department of Internal Medicine I — Endocrinology and MetabolismUniversity of HeidelbergHeidelbergGermany

Personalised recommendations