Review article : Hypercalcaemia of malignancy

Abstract

This article reviews the incidence and clinical features of hypercalcaemia caused by malignancy. The pathogenesis is examined, looking at recent evidence on endocrinological processes, particularly parathyroid hormone related protein. Finally the article reviews current thinking on treatment.

Keywords

diphosphonates drug therapy hypercalcaemia neoplasms palliative treatment parenteral infusion

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References

Christensson T. , Hellström K. , Wengle B. , Alveryd A. , Wikland B. Prevalence of hypercalcaemia in a health screening in Stockholm. Acta Med Scand 1976; 200: 131-37.

Fisken RA , Heath DA , Bold AM

Hypercalcaemia - a hospital survey

Q J Med 1980; 196: 405-18.

Fisken RA , Heath DA , Somers S. , Bold AM Hypercalcaemia in hospital patients. Clinical and diagnostic aspects. Lancet 1981; 1: 202-207.

Thomas AN , Loken HF , Gordan GS , Goldman L. Hypercalcaemia of metastatic breast cancer. Surg Forum 1960; 11: 70-71.

McMahon AJ Oesophageal carcinoma and hypercalcaemia: a clinical study. European Journal of Surgical Oncology 1987; 13: 399-403.

Coggeshall J. , Merrill W. , Hande K. , Prez RD Implications of hypercalcaemia with respect to diagnosis and treatment of lung cancer. Am J Med 1986; 80: 325-28.

Blomqvist CP Malignant hypercalcaemia - a hospital survey . Acta Med Scand 1986; 220: 455-63.

Percival RC , Yates Ajp , Gray Res et al. Mechanisms of malignant hypercalcaemia in carcinoma of the breast . Br Med J 1985; 291: 776-79.

Bender RA , Hansen H. Hypercalcaemia in bronchogenic carcinoma: a prospective study of 200 cases . Ann Intern Med 1974; 80: 205-208.

10.

Albright F. Case records of the Massachusetts General Hospital (case 27401 ) . N Engl J Med 1941; 225: 789-91.

11.

Benson RCJr , Riggs BL , Pickard BM , Arnaud CD Radioimmunoassay of parathyroid hormone in hypercalcaemic patients with malignant disease. Am J Med 1974; 56: 821-26.

12.

Roof BS , Carpenter B. , Fink DJ , Gordan GS Some thoughts on the nature of ectopic parathyroid hormone. Am J Med 1971; 50: 686-91.

13.

Simpson EL , Mundy GR , D'Souza SM , Ibbotson KJ , Bockman R. , Jacobs JW Absence of parathyroid hormone messenger RNA in nonparathyroid tumours associated with hypercalcaemia. N Engl J Med 1983; 309: 325-30.

14.

Yoshida M. , Miyoshi I. , Hinuma Y. Isolation and characterisation of retrovirus from cell lines of human adult T-cell leukaemia and its implication in the disease. Proc Natl Acad Sci USA 1982; 79: 2031-35.

15.

Fetchick DA , Bertolini DR , Sarin PS , Weintraub ST , Mundy GR , Dunn JF Production of 1.25 dihydroxy vitamin D3 by human T cell lymphotrophic virus-1-transformed lymphocytes . J Clin Invest 1986, 78: 592-96.

16.

Fukomoto S. , Matsumoto T. , Ikeda K. et al. Clinical evaluation of calcium metabolism in adult T-cell leukaemia/lymphoma. Arch Intern Med 1988; 148: 921-25.

17.

Klein DC , Raisz LG Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology 1970; 86: 1436-40.

18.

Tashjian AH Jr. Role of prostaglandins in the production of hypercalcaemia by tumours. Cancer Res 1978 ; 38: 4138-41.

19.

Gowen M. , Wood DW , Ihrie EJ , McQuire MD , Russell Rgg. An interleukin-1 like factor stimulates bone resorption in vitro. Nature 1983; 306: 378-80.

20.

Bertolini DR , Medwin GE , Bringman TS , Smith DD , Mundy GR Stimulation of bone resorption and inhibition of bone formation in vitro by human tissue necrosis factor. Nature 1986; 319: 516-18.

21.

Mundy GR , Raisz LG , Cooper RA , Schechter GP , Salmon SE Evidence for the secretion of an osteoclast stimulating factor in myeloma . N Engl J Med 1974; 291: 1041-46.

22.

Ibbotson KJ , Twardzik DR , D'Souza SM , Hargreaves WR , Todaro GJ , Mundy GR Synthetic transforming growth factor alpha stimulates bone resorption in vitro . Science 1985; 228: 1007-1009.

23.

D'Souza SM , Ibbotson KJ , Smith DD , Mundy GR Production of a macromolecular bone resorbing factor by the hypercalcaemic variant of the Walker rat carcinosarcoma. Endocrinology 1984; 115: 1746-52.

24.

Tashjian AHJr , Levine L. Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria. Biochem Biophys Res Comm 1978; 85: 966-75.

25.

Tashjian AH Jr, Hohmann EL , Antoniades HN , Levine L. Platelet derived growth factor stimulates bone resorption via a prostaglandin mediated mechanism . Endocrinology 1982; 111: 118-24.

26.

Stewart AF , Horst R. , Deftos LJ , Cadman EC , Lang R. , Broadus AE Biochemical evaluation of patients with cancer-associated hypercalcaemia. Evidence for humoral and nonhumoral groups. N Engl J Med 1980; 303: 1377-81.

27.

Loveridge N. , Kent GN , Heath DA , Jones EL Parathyroid hormone-like bioactivity in a patient with severe osteitis fibrosa cystica due to malignancy: renotrophic actions of a tumour extract as assessed by cytochemical bioassay . Clin Endocrinol 1980; 22: 135-46.

28.

Stewart AF , Insogna KL , Goltzman D. , Broadus AE Identification of adenylate-cyclase-stimulating activity and cytochemical glucose-6- phosphate dehydrogenase-stimulating activity in extracts of tumours from patients with humoral hypercalcaemia of malignancy. Proc NatAcad Sci USA 1983; 80: 1454-58.

29.

Rodan SB , Insogna KL , Vignery Amc et al. Factors associated with humoral hypercalcaemia of malignancy stimulate adenylate cyclase in osteoblastic cells. J Clin Invest 1983; 72: 1511-15.

30.

Docherty HM , Heath DA Multiple forms of active PTH-like problems in a human tumour. Journal of Molecular Oncology 1988 (in press).

31.

Suva LJ , Winslow GA , Wettenhall Reh et al. A parathyroid hormone-related protein implicated in malignant hypercalcaemia: cloning and expression. Science 1987; 237: 893-96.

32.

Mangin M. , Webb AC , Dreyer BE et al. Identification of a CDNA encoding a parathyroid hormone-like peptide from a human tumour associated with humoral hypercalcaemia of malignancy . Proc Natl Acad Sci USA 1988; 85: 597-601.

33.

Horiuchi N. , Caulfield MP , Fisher JE et al. Similarity of synthetic peptide from human tumour to parathyroid hormone in vivo and in vitro. Science 1987; 238: 1566-68.

34.

Kemp BE , Moseley JM , Rodda CP Parathyroid hormone-related protein of malignancy: active synthetic fragments . Science 1987; 238: 1568-70.

35.

Stewart AF , Wu T. , Goumas D. , Burtis WJ , Broadus AE N-terminal amino acid sequence of two novel tumour-derived adenylate cyclase-stimulating proteins: identification of parathyroid hormone-like and parathyroid hormone-unlike domains. Biochem Biophys Res Commun 1987; 146: 672-78.

36.

Strewler GJ , Stern PH , Jacobs JW et al. Parathyroid hormone-like protein from human renal carcinoma cells: structural and functional homology with parathyroid hormone. J Clin Invest 1987 ; 80: 1803-807.

37.

Stewart AF , Insogna KL , Burtis WJ et al. Frequency and partial characterisation of adenylate cyclase-stimulating activity in tumours associated with humoral hypercalcaemia of malignancy. Journal of Bone Mineral Research 1986; 1: 267-76.

38.

Merendino JJ Jr , Insogna KL , Milstone LM , Broadus AE , Stewart AF A parathyroid hormone-like protein from cultured human keratinocytes. Science 1986; 231: 388-90.

39.

Docherty HM , Dixon-Lewis MJ , Blight A. , Heath DA Characteristics of a PTH-like factor from human keratinocytes. J Endocrinol 1987; 112 (Suppl. 98A).

40.

Wu TL , Insogna KL , Hough LM , Milstone L. , Stewart AF Skin-derived fibroblasts respond to human PTH-like adenylate cyclase-stimulating proteins. J Clin Endocrinol Metab 1987; 65: 105-109.

41.

Benabe JE , Martinez-Maldonado M. Hypercalcaemic nephropathy. Arch Intern Med 1978; 138: 777-79.

42.

Baylis PH , Milles JJ , Wilkinson R. , Heath DA Vasopressin function in hypercalcaemia. Clin Endocrinol 1981; 15: 343-51.

43.

Suki WN , Yium JJ , Van Minden M , SallerHerbert C. , Eknoyan G. , Martinez-Maldonado M. Acute treatment of hypercalcaemia with furosemide. N Engl J Med 1970; 283: 836-40.

44.

Mannheimer IH Hypercalcaemia of breast cancer: management with cortico steroids. Cancer 1965; 18: 679-91.

45.

Myers Wpl. Cortisone in the treatment of hypercalcaemia in neoplastic disease . Cancer 1958; 11: 83-88.

46.

Fulmer DH , Dimich AB , Rothchild EO , Myers Wpl. Treatment of hypercalcaemia. Comparison of intravenously administered phosphate, sulphate and hydrocortisone. Arch Intern Med 1972; 129: 923-30.

47.

Mundy GR , Wilkinson R. , Heath DA Comparative study of available medical therapy for hypercalcaemia of malignancy . Am J Med 1983; 74: 421-32.

48.

Thalassinos NC , Joplin GF Failure of corticosteroid therapy to correct the hypercalcaemia of malignant disease. Lancet 1970; 2: 537-39.

49.

Percival RC , Yates AJ , Gray RE , Neal FE , Forrester AR , Kanis JA Role of glucocorticoids in management of malignant hypercalcaemia. Br Med J 1984; 289: 287.

50.

Editorial. Management of severe hypercalcaemia. Br Med J 1980; 280: 204-205.

51.

Selby PC , Peacock M. , Marshall DH Hypercalcaemia - management. Br J Hosp Med 1984; 31: 186-97.

52.

Hosking DJ , Gilson D.

Comparison of the renal and skeletal actions of calcitonin in the treatment of severe hypercalcaemia of malignancy Q

J Med 1984; 211: 359-69.

53.

Binstock ML , Mundy GR Effect of calcitonin and glucocorticoids in combination on the hypercalcaemia of malignancy. Ann Intern Med 1980; 93: 269-72.

54.

Ralston SH , Gardner MD , Dryburgh FJ , Jenkins AS , Cowan RA , Boyle IT Comparison of aminohydroxypropylidene diphosphonate, mithramycin, and corticosteroids/calcitonin on treatment of cancer associated hypercalcaemia . Lancet 1985; 2: 907-10.

55.

Heath DA The use of inorganic phosphate in the management of hypercalcaemia . Metabolic Bone Disease and Related Research 1980; 2: 213-15.

56.

Morton AR , Cantrill JA , Craig AE , Howell A. , Davies M. , Anderson DC Single dose versus daily intravenous aminohydroxypropylidene diphosphonate (APD) for the hypercalcaemia of malignancy. Br Med J 1988; 296: 811-14.

57.

Hasling C. , Charles P. , Mosekilde L. Etidronate disodium in the management of malignancy related hypercalcaemia . Am J Med 1987; 82 (Suppl. 214): 51-54.

58.

Witte RS , Koeller J. , Davis TE et al. Clodronate. A randomised study in the treatment of cancer related hypercalcaemia. Arch Intern Med 1987; 47: 937-39.

59.

Davies Jre , Heath DA Comparison of different close regimes of aminohydroxypropylidene-1,1-diphosphonate (APD) in hypercalcaemia of malignancy. Submitted for publication.

60.

Singer FR , Villanueva R. , Yuen H. Randomised trial of intravenous etidronate disodium and subcutaneous salmon calcitonin in malignant hypercalcaemia. 70th Annual Meeting of the Endocrine Society, 1988.

61.

Rastad J. , Benson L. , Johansson H. et al. Clodronate treatment in patients with malignancy-associated hypercalcaemia. Acta Med Scand 1987; 221: 489-94.