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Current Management of Malignant Hypercalcaemia

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Summary

The pathogenic mechanisms causing malignant hypercalcaemia are primarily increased bone calcium mobilisation and renal calcium retention. In some reticuloendothelial malignancies, enhanced intestinal calcium absorption may also play a role.

Malignant hypercalcaemia is a life-threatening condition, and there are many patients with malignancy in whom suppression of this complication is most desirable. In such cases, successful management of the hypercalcaemia will enable the overall treatment aims, such as tumour removal or ablation, to be achieved.

Acute treatment involves the rapid lowering of serum calcium from potentially fatal concentrations, and comprises the use of intravenous rehydration, calcitonin and diphosphonates. In the longer term, other measures may be introduced to maintain and control the calcium concentration while specific antitumour therapy is instituted.

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References

  • Bennett A, Charlier EM, McDonald AM, Simpson JS, Stamford IF, et al. Prostaglandins and breast cancer. Lancet 2: 624–626, 1977

    Article  PubMed  CAS  Google Scholar 

  • Binstock ML, Mundy GR. Effect of calcitonin and glucocorticoids in combination in malignant hypercalcaemia. Annals of Internal Medicine 93: 269–272, 1980

    PubMed  CAS  Google Scholar 

  • Boonekamp PM, van der Wee-Pals LJA, van Wiji-fan Lennep MLL, Thesing CW, Bijvoet OLM. Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone and Mineral 1: 27–39, 1986

    PubMed  CAS  Google Scholar 

  • Chapuy MC, Meunier PJ, Alexandre CM, Vignon EP. Effects of disodium dichloromethylene diphosphonate on hypercalcaemia produced by bone metastases. Journal of Clinical Investigation 65: 1243–1247, 1980

    Article  PubMed  CAS  Google Scholar 

  • Coombes RC, Neville AM, Bondy PK, Powles JJ, et al. Failure of indomethacin to reduce hydroxyproline excretion or hypercalcaemia in patients with breast cancer. Prostaglandins 12: 1027–1035, 1976

    Article  PubMed  CAS  Google Scholar 

  • Davies M, Mawer EB, Hayes ME, Lumb GA. Abnormal vitamin D metabolism in Hodgkin’s lymphoma. Lancet 2: 1186–1188, 1985

    Article  Google Scholar 

  • Feldman RS, Krieger NS, Tashjian Jr AH. Effects of parathyroid hormone and calcitonin on osteoclast formation in vitro. Endocrinology 107: 1137–1143, 1980

    Article  PubMed  CAS  Google Scholar 

  • Fetchick DA, Bertolini DR, Sarin PS, Weintraub ST, Mundy GR, et al. Production of 1,25-dihydroxyvitamin D3 by human T cell lymphotrophic virus-1-transformed lymphocytes. Journal of Clinical Investigation 78: 592–596, 1986

    Article  PubMed  CAS  Google Scholar 

  • Foster GV, Doyle FH, Bordier P, Matrajt H. In vivo effect of thyrocalcitonin on bone. In Milhaud et al. (Eds) Les tissus calcifies, Ve Symposium Européen, pp. 173–177, Société d’Edition d’Enseignement Superier, Paris, 1969

    Google Scholar 

  • Goltzman D, Stewart AF, Broadus AE. Malignancy-associated hypercalcaemia: evaluation with a cytochemical bioassay for parathyroid hormone. Journal of Clinical Endocrinology and Metabolism 53: 899–904, 1981

    Article  PubMed  CAS  Google Scholar 

  • Gowen M, Wood DD, Ihrie EJ, McGuire MKB, Russell RGG. An interleukin-1 like factor stimulates bone résorption in vitro. Nature 360: 378–380, 1983

    Article  Google Scholar 

  • Hasling C, Charles P, Mosekilde L. Etidronate disodium in the management of malignancy-related hypercalcaemia. American Journal of Medicine 82: (Suppl. 2A): 51–54, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hosking DJ, Gilson D. Comparison of the renal and skeletal actions of calcitonin in the treatment of severe hypercalcaemia of malignancy. Quarterly Journal of Medicine 53: 359–368, 1984

    PubMed  CAS  Google Scholar 

  • Hosking DJ, Heller SR. Quantitation of the renal effect of calcitonin in the hypercalcaemia of malignancy. European Journal of Pharmacology 31: 27–31, 1986

    Article  CAS  Google Scholar 

  • Ibbotson KJ, D’Souza SM, Ng KW, Osborne CK, Niall M, et al. Tumor-derived growth factor increases bone resorption in a tumor associated with humoral hypercalcaemia of maliganncy. Science 221: 1292–1294, 1983

    Article  PubMed  CAS  Google Scholar 

  • Jacobs TP, Gordon AC, Silverberg SJ, Shane E, Reich L, et al. Neoplastic hypercalcaemia: physiologic response to intravenous etidronate disodium. American Journal of Medicine 82 (Suppl. 2A): 42–50, 1987

    Article  PubMed  CAS  Google Scholar 

  • Jung A. Comparison of two parenteral diphosphonates in hypercalcaemia of malignancy. American Journal of Medicine 72: 221–226, 1982

    Article  PubMed  CAS  Google Scholar 

  • Klein DC, Raisz LG. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology 85: 657–661, 1970

    Google Scholar 

  • Kukreja SC, Shemerdiak WP, Lad TE, Johnson PA, et al. Elevated nephrogenous cyclic AMP with normal serum parathyroid hormone levels in patients with lung cancer. Journal of Clinical Endocrinology and Metabolism 51: 167–169, 1980

    Article  PubMed  CAS  Google Scholar 

  • Lafferty FW. Pseudohyperparathyroidism. Medicine (Baltimore) 45: 247–260, 1966

    Article  CAS  Google Scholar 

  • Mundy GR, Martin TJ. The hypercalcaemia of malignancy: pathogenesis and management. Metabolism 31: 1247–1277, 1982

    Article  PubMed  CAS  Google Scholar 

  • Mundy GR, Raisz LG, Cooper RA, Schechter GP, Salmon SE, et al. Evidence for the secretion of an osteoclast stimulating factor in myeloma. New England Journal of Medicine 291: 1041–1046, 1974

    Article  PubMed  CAS  Google Scholar 

  • Mundy GR, Rick ME, Turcotte R, Kowalski MA, et al. Pathogenesis of hypercalcaemia in lymphosarcoma cell leukaemia: role of an osteoclast activating factor-like substance and mechanism of action for glucocorticoid therapy. American Journal of Medicine 65: 600–606, 1978

    Article  PubMed  CAS  Google Scholar 

  • Parsons V, Baum M, Self M. Effect of mithramycin on calcium and hydroxyproline metabolism in patients with malignant disease. British Medical Journal 1: 474–477, 1967

    Article  PubMed  CAS  Google Scholar 

  • Percival RC, Yates AJ, Gray TE, Neal FE, Forrest AR, et al. Role of glucocorticoids in management of malignant hypercalcaemia. British Medical Journal 289: 287, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ralston S, Fogelman I, Gardner MD, Boyle IT. Hypercalcaemia and metastatic bone disease: is there a causal link? Lancet 2: 903–905, 1982

    Article  PubMed  CAS  Google Scholar 

  • Ralston SH, Fogelman I, Gardner MD, Dryburgh FJ, Cowan RA, et al. Hypercalcaemia of malignancy: evidence for a non-parathyroid humoral agent with an effect on renal tubular handling of calcium. Clinical Science 66: 187–191, 1984

    PubMed  CAS  Google Scholar 

  • Russell RGG, Smith R, Preston C, Walton RJ, Woods CF. Diphosphonates in Paget’s disease. Lancet 1: 894–898, 1974

    PubMed  CAS  Google Scholar 

  • Ryzen E, Rude RK, Elbaum N, Singer FR. Use of intravenous etidronate in the treatment of hypercalcaemia. In Garattini (Ed.) Bone resorption, metastasis, and diphosphonates, pp. 99–108, Raven Press, New York, 1985

    Google Scholar 

  • Seyberth HW, Segre GV, Morgan JL, Sweetman BJ, Potts Jr JT, et al. Prostaglandins as mediators of hypercalcaemia associated with certain types of cancer. New England Journal of Medicine 293: 1278–1283, 1975

    Article  PubMed  CAS  Google Scholar 

  • Stevenson JC. Malignant hypercalcaemia. British Medical Journal 291: 421–422, 1985

    Article  PubMed  CAS  Google Scholar 

  • Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, et al. Biochemical evaluation of patients with cancer-associated hypercalcaemia: evidence for humoral and non-humoral groups. New England Journal of Medicine 303: 1377–1383, 1980

    Article  PubMed  CAS  Google Scholar 

  • Suki WN, Yium JJ, Von Mindern A, Sailer-Herbert C, Eknoyan G, et al. Acute treatment of hypercalcaemia with furosemide. New England Journal of Medicine 283: 836–840, 1970

    Article  PubMed  CAS  Google Scholar 

  • Tashjian Jr AH. Prostaglandins, hypercalcaemia and cancer. New England Journal of Medicine 293: 1317–1318, 1975

    Article  PubMed  Google Scholar 

  • Tashjian Jr AH, Voelkel EF, Levine L, Goldhaber P. Evidence that the bone resorption-stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E2: a new model for the hypercalcaemia of cancer. Journal of Experimental Medicine 136: 1329–1343, 1972

    Article  PubMed  CAS  Google Scholar 

  • Tashjian AH, Wright DR, Ivey JL, Pont A. Calcitonin binding sites in bone. Relationships to biological response and escape. Recent Progress in Hormone Research 34: 285–334, 1978

    PubMed  CAS  Google Scholar 

  • Thalassinos NC, Joplin G. Failure of corticosteroid therapy to direct the hypercalcaemia of malignant disease. Lancet 2: 537–538, 1970

    Article  PubMed  CAS  Google Scholar 

  • Todaro GF, Fryling C, De Larco JE. Transforming growth factors (TGFs) produced by certain human tumor cells: polypeptides that interact with epidermal growth factor (EGF) receptors. Proceedings of the National Academy of Sciences (USA) 77: 5058–5062, 1980

    Article  Google Scholar 

  • Van Breukelen FJM, Bijvoet OLM, van Oosterom AT. Inhibition of osteolytic bone lesions by (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Lancet 1: 803–805, 1979

    Article  PubMed  Google Scholar 

Download references

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  1. Cavendish Clinic, 21 Wellington Road, London, NW8 9SQ, England

    John C. Stevenson

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Stevenson, J.C. Current Management of Malignant Hypercalcaemia. Drugs 36, 229–238 (1988). https://doi.org/10.2165/00003495-198836020-00005

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