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.
Christensson T., Hellström K., Wengle B., Alveryd A., Wikland B.Prevalence of hypercalcaemia in a health screening in Stockholm. Acta Med Scand1976; 200: 131-37.
2.
Fisken RA, Heath DA, Bold AMHypercalcaemia - a hospital surveyQ J Med1980; 196: 405-18.
3.
Fisken RA, Heath DA, Somers S., Bold AMHypercalcaemia in hospital patients. Clinical and diagnostic aspects. Lancet1981; 1: 202-207.
4.
Thomas AN, Loken HF, Gordan GS, Goldman L.Hypercalcaemia of metastatic breast cancer. Surg Forum1960; 11: 70-71.
5.
McMahon AJOesophageal carcinoma and hypercalcaemia: a clinical study. European Journal of Surgical Oncology1987; 13: 399-403.
6.
Coggeshall J. , Merrill W., Hande K., Prez RDImplications of hypercalcaemia with respect to diagnosis and treatment of lung cancer. Am J Med1986; 80: 325-28.
7.
Blomqvist CPMalignant hypercalcaemia - a hospital survey . Acta Med Scand1986; 220: 455-63.
8.
Percival RC, Yates Ajp, Gray Res et al. Mechanisms of malignant hypercalcaemia in carcinoma of the breast . Br Med J1985; 291: 776-79.
9.
Bender RA, Hansen H.Hypercalcaemia in bronchogenic carcinoma: a prospective study of 200 cases . Ann Intern Med1974; 80: 205-208.
10.
Albright F.Case records of the Massachusetts General Hospital (case 27401 ) . N Engl J Med1941; 225: 789-91.
11.
Benson RCJr , Riggs BL , Pickard BM, Arnaud CDRadioimmunoassay of parathyroid hormone in hypercalcaemic patients with malignant disease. Am J Med1974; 56: 821-26.
12.
Roof BS, Carpenter B., Fink DJ, Gordan GSSome thoughts on the nature of ectopic parathyroid hormone. Am J Med1971; 50: 686-91.
13.
Simpson EL, Mundy GR, D'Souza SM, Ibbotson KJ, Bockman R., Jacobs JWAbsence of parathyroid hormone messenger RNA in nonparathyroid tumours associated with hypercalcaemia. N Engl J Med1983; 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 USA1982; 79: 2031-35.
15.
Fetchick DA , Bertolini DR, Sarin PS, Weintraub ST, Mundy GR, Dunn JFProduction of 1.25 dihydroxy vitamin D3 by human T cell lymphotrophic virus-1-transformed lymphocytes . J Clin Invest1986, 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 Med1988; 148: 921-25.
17.
Klein DC, Raisz LGProstaglandins: stimulation of bone resorption in tissue culture. Endocrinology1970; 86: 1436-40.
18.
Tashjian AH Jr.Role of prostaglandins in the production of hypercalcaemia by tumours. Cancer Res1978 ; 38: 4138-41.
19.
Gowen M., Wood DW, Ihrie EJ, McQuire MD, Russell Rgg.An interleukin-1 like factor stimulates bone resorption in vitro. Nature1983; 306: 378-80.
20.
Bertolini DR , Medwin GE, Bringman TS, Smith DD, Mundy GRStimulation of bone resorption and inhibition of bone formation in vitro by human tissue necrosis factor. Nature1986; 319: 516-18.
21.
Mundy GR, Raisz LG, Cooper RA, Schechter GP, Salmon SEEvidence for the secretion of an osteoclast stimulating factor in myeloma . N Engl J Med1974; 291: 1041-46.
D'Souza SM, Ibbotson KJ, Smith DD, Mundy GRProduction of a macromolecular bone resorbing factor by the hypercalcaemic variant of the Walker rat carcinosarcoma. Endocrinology1984; 115: 1746-52.
24.
Tashjian AHJr , Levine L.Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria. Biochem Biophys Res Comm1978; 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 . Endocrinology1982; 111: 118-24.
26.
Stewart AF, Horst R., Deftos LJ, Cadman EC, Lang R., Broadus AEBiochemical evaluation of patients with cancer-associated hypercalcaemia. Evidence for humoral and nonhumoral groups. N Engl J Med1980; 303: 1377-81.
27.
Loveridge N. , Kent GN, Heath DA, Jones ELParathyroid 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 Endocrinol1980; 22: 135-46.
28.
Stewart AF, Insogna KL, Goltzman D., Broadus AEIdentification 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 USA1983; 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 Invest1983; 72: 1511-15.
30.
Docherty HM , Heath DAMultiple forms of active PTH-like problems in a human tumour. Journal of Molecular Oncology1988 (in press).
31.
Suva LJ, Winslow GA, Wettenhall Reh et al. A parathyroid hormone-related protein implicated in malignant hypercalcaemia: cloning and expression. Science1987; 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 USA1988; 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. Science1987; 238: 1566-68.
34.
Kemp BE, Moseley JM, Rodda CPParathyroid hormone-related protein of malignancy: active synthetic fragments . Science1987; 238: 1568-70.
35.
Stewart AF, Wu T., Goumas D., Burtis WJ, Broadus AEN-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 Commun1987; 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 Invest1987 ; 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 Research1986; 1: 267-76.
38.
Merendino JJ Jr, Insogna KL, Milstone LM, Broadus AE, Stewart AFA parathyroid hormone-like protein from cultured human keratinocytes. Science1986; 231: 388-90.
39.
Docherty HM , Dixon-Lewis MJ, Blight A., Heath DACharacteristics of a PTH-like factor from human keratinocytes. J Endocrinol1987; 112 (Suppl. 98A).
40.
Wu TL, Insogna KL, Hough LM, Milstone L., Stewart AFSkin-derived fibroblasts respond to human PTH-like adenylate cyclase-stimulating proteins. J Clin Endocrinol Metab1987; 65: 105-109.
41.
Benabe JE, Martinez-Maldonado M.Hypercalcaemic nephropathy. Arch Intern Med1978; 138: 777-79.
42.
Baylis PH, Milles JJ, Wilkinson R., Heath DAVasopressin function in hypercalcaemia. Clin Endocrinol1981; 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 Med1970; 283: 836-40.
44.
Mannheimer IHHypercalcaemia of breast cancer: management with cortico steroids. Cancer1965; 18: 679-91.
45.
Myers Wpl.Cortisone in the treatment of hypercalcaemia in neoplastic disease . Cancer1958; 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 Med1972; 129: 923-30.
47.
Mundy GR, Wilkinson R., Heath DAComparative study of available medical therapy for hypercalcaemia of malignancy . Am J Med1983; 74: 421-32.
48.
Thalassinos NC, Joplin GFFailure of corticosteroid therapy to correct the hypercalcaemia of malignant disease. Lancet1970; 2: 537-39.
49.
Percival RC , Yates AJ, Gray RE, Neal FE, Forrester AR, Kanis JARole of glucocorticoids in management of malignant hypercalcaemia. Br Med J1984; 289: 287.
50.
Editorial.Management of severe hypercalcaemia. Br Med J1980; 280: 204-205.
Hosking DJ, Gilson D.Comparison of the renal and skeletal actions of calcitonin in the treatment of severe hypercalcaemia of malignancy QJ Med1984; 211: 359-69.
53.
Binstock ML , Mundy GREffect of calcitonin and glucocorticoids in combination on the hypercalcaemia of malignancy. Ann Intern Med1980; 93: 269-72.
54.
Ralston SH, Gardner MD, Dryburgh FJ, Jenkins AS, Cowan RA, Boyle ITComparison of aminohydroxypropylidene diphosphonate, mithramycin, and corticosteroids/calcitonin on treatment of cancer associated hypercalcaemia . Lancet1985; 2: 907-10.
55.
Heath DAThe use of inorganic phosphate in the management of hypercalcaemia . Metabolic Bone Disease and Related Research1980; 2: 213-15.
56.
Morton AR, Cantrill JA, Craig AE, Howell A., Davies M., Anderson DCSingle dose versus daily intravenous aminohydroxypropylidene diphosphonate (APD) for the hypercalcaemia of malignancy. Br Med J1988; 296: 811-14.
57.
Hasling C., Charles P., Mosekilde L.Etidronate disodium in the management of malignancy related hypercalcaemia . Am J Med1987; 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 Med1987; 47: 937-39.
59.
Davies Jre, Heath DAComparison 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 Scand1987; 221: 489-94.
