Hypercalcemia in cancer patients: Pathobiology and management

Hormone and Metabolic Research

Volumn 42, Issue 3, 2010, Pages 153-164

  Santarpia, L ^a,b   Koch, C A ^c   Sarlis, N J ^d  

^a Istituto Toscana Tumori ^*  (Italy)

^b UNIVERSITY OF TEXAS   (United States)

^c UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

^d SANOFI   (France)

Author keywords

Cancer; Hypercalcemia; Malignancy; Therapy

Indexed keywords

AMGN 0007; AMINOGLYCOSIDE DERIVATIVE; AMPHOTERICIN B; ANTACID AGENT; CALCIUM; CINACALCET; CYCLOSPORIN; DENOSUMAB; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; ETIDRONIC ACID; FUROSEMIDE; GALLIUM NITRATE; GLUCAGON; HYDROCORTISONE; INTERLEUKIN 1; INTERLEUKIN 6; INTERLEUKIN 7; MITHRAMYCIN; PAMIDRONIC ACID; PARATHYROID HORMONE RELATED PROTEIN; POTASSIUM DIHYDROGEN PHOSPHATE; POTASSIUM SPARING DIURETIC AGENT; PREDNISONE; RETINOIC ACID DERIVATIVE; SALCATONIN; SODIUM DIHYDROGEN PHOSPHATE; SUCRALFATE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZOLEDRONIC ACID;

ANEMIA; BODY TEMPERATURE; BREAST CANCER; BRONCHOSPASM; CALCIUM BLOOD LEVEL; CALCIUM METABOLISM; CANCER PATIENT; CANCER THERAPY; CLINICAL FEATURE; CLINICAL TRIAL; COMORBIDITY; CREATININE BLOOD LEVEL; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG CONTRAINDICATION; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EXCRETION; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG MEGADOSE; DRUG TOLERABILITY; DYSPNEA; FEVER; GLOMERULUS FILTRATION RATE; HEALTH CARE PERSONNEL; HUMAN; HYPERCALCEMIA; HYPERGLYCEMIA; HYPERPHOSPHATEMIA; HYPOCALCEMIA; HYPOKALEMIA; HYPOMAGNESEMIA; HYPOPHOSPHATEMIA; JAW OSTEONECROSIS; KIDNEY DISEASE; KIDNEY FAILURE; LABORATORY TEST; LEUKOPENIA; LUNG CANCER; METABOLIC DISORDER; MULTIPLE MYELOMA; MUSCLE SPASM; MYALGIA; NAUSEA; NEPHROTIC SYNDROME; NEPHROTOXICITY; PAIN; PARATHYROID HORMONE BLOOD LEVEL; PARESTHESIA; PATHOLOGY; PATHOPHYSIOLOGY; PERIODONTAL DISEASE; PHOSPHATE BLOOD LEVEL; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SALURESIS; SIDE EFFECT; SINGLE DRUG DOSE; SOLID TUMOR; SWELLING; TACHYPHYLAXIS; TREATMENT CONTRAINDICATION; TREATMENT DURATION; TREATMENT RESPONSE; VOMITING; WHEEZING;

ANTINEOPLASTIC AGENTS; HUMANS; HYPERCALCEMIA; IMMOBILIZATION; NEOPLASMS; PARATHYROID HORMONE-RELATED PROTEIN;

EID: 77949279840     PISSN: 00185043     EISSN: 14394286     Source Type: Journal    
DOI: 10.1055/s-0029-1241821     Document Type: Review

References (90)

1. Chan FK, Koberle LM, Thys-Jacobs S, Bilezikian JP. Differential diagnosis, causes, and management of hypercalcemia. Curr Probl Surg 1997 34 445-523
2. Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med 2004 27 153-160
3. Nishi S, Barbagelata N, Atar S, Birnbaum Y, Tuero E. Hypercalcemia- induced ST-segment elevation mimicking acute myocardial infarction. J Electrocardiol 2006 39 298-300
4. Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am 1995 79 79-92
5. Falk S, Kratzsch J, Paschke R, Koch CA. Hypercalcemia as a result of sarcoidosis with normal serum concentrations of vitamin D. Med Sci Monit 2007 13 133-136
6. Suda T, Kobayashi K, Jimi E, Udagawa N, Takahashi N. The molecular basis of osteoclast differentiation and activation. Novartis Found Symp 2001 232 235-247 discussion 247250
7. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 2000 15 2-12
8. Schett G, Hayer S, Zwerina J, Redlich K, Smolen JS. Mechanisms of Disease: the link between RANKL and arthritic bone disease. Nat Clin Pract Rheumatol 2005 1 47-54
9. McCollum CR, Pitman K, Bigler SA, Vijayakumar V, Flessner M, Jenkins J, Horn M, Arnold A, Koch CA. Hypercalcemia of 26.5mg: Isolated parathyroid malignancy or hereditary syndrome? J Invest Med 2009 57 S327
10. Fernandez-Ranvier GG, Khanafshar E, Jensen K, Zarnegar R, Lee J, Kebebew E, Duh QY, Clark OH. Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis? Cancer 2007 110 255-264
11. Robert JH, Trombetti A, Garcia A, Pache JC, Herrmann F, Spiliopoulos A, Rizzoli R. Primary hyperparathyroidism: can parathyroid carcinoma be anticipated on clinical and biochemical grounds? Report of 9 cases and review of the literature. Ann Surg Oncol 2005 12 1-7
12. Wysolmerski JJ, Broadus AE. Hypercalcemia of malignancy: the central role of parathyroid hormone-related protein. Annu Rev Med 1994 45 189-200
13. Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer associated hypercalcemia: evidence for humoral and nonhumoral groups. N Engl J Med 1980 303 1377-1383
14. Dunbar ME, Wysolmerski JJ, Broadus AE. Parathyroid hormone-related protein: from hypercalcemia of malignancy to developmental regulatory molecule. Am J Med Sci 1996 312 287-294
15. Strewler GJ. Mechanisms of disease The physiology of parathyroid hormone-related protein. N Engl J Med 2000 342 177-185
16. Chorev M. Parathyroid hormone 1 receptor: Insights into structure and function. Receptors Channels. 2002 8 219-242
17. Philbrick WM, Wysolmerski JJ, Galbraith S, Holt E, Orloff JJ, Yang KH, Vasavada RC, Weir EC, Broadus AE, Stewart AF. Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev 1996 76 127-173
18. Kronenberg HM, Chung U. The parathyroid hormone-related protein and Indian hedgehog feedback loop in the growth plate. Novartis Found Symp 2001 232 144-152 discussion 152157
19. Kimura S, Nishimura Y, Yamaguchi K, Nagasaki K, Shimada K, Uchida H. A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia. J Clin Endocrinol Metab 1990 70 1559-1563
20. Al-Rashid RA, Cress C. Hypercalcemia associated with neuroblastoma. Am J Dis Child 1979 133 838-341
21. Mitlak BH, Hutchison JS, Kaufman SD, Nussbaum SR. Parathyroid hormone related peptide mediates hypercalcemia in an islet cell tumor of the pancreas. Horm Metab Res 1991 23 344-346
22. Prager D, Rosenblatt JD, Ejima E. Hypercalcemia, parathyroid hormone-related protein expression and human T-cell leukemia virus infection. Leuk Lymphoma 1994 14 395-400
23. Ikeda K, Ogata E. Humoral hypercalcemia of malignancy: some enigmas on the clinical features. J Cell Biochem 1995 57 384-391
24. Goldring SR, Goldring MB. Cytokines and skeletal physiology. Clin Orthop 1996 324 13-23
25. Uy HL, Mundy GR, Boyce BF, Story BM, Dunstan CR, Yin JJ, Roodman GD, Guise TA. Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo. Cancer Res 1997 57 3194-3199
26. de la Mata J, Uy HL, Guise TA, Story B, Boyce BF, Mundy GR, Roodman GD. Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo. J Clin Invest 1995 95 2846-2852
27. Hewison M, Kantorovich V, Liker HR, Van Herle AJ, Cohan P, Zehnder D, Adams JS. Vitamin D-mediated hypercalcemia in lymphoma: Evidence for hormone production by tumor-adjacent macrophages. J Bone Miner Res 2003 18 (3) 579-582
28. Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, OKeefe PF, Ramnaraine ML, Clohisy DR, Mntyh PW. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nature Med 2000 6 521-528
29. Budayr AA, Nissenson RA, Klein RF, Pun KK, Clark OH, Diep D, Arnaud CD, Strewler GJ. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcemia. Ann Intern Med 1989 111 807-812
30. Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RP Jr, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF. Immunochemical characterization of circulating parathyroid hormone- related protein in patients with humoral hypercalcemia of cancer. N Engl J Med 1990 322 1106-1112
31. Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, Brabbs AC, van Beek EJ, Holen I, Skerry TM, Dunstan CR, Russell GR, Van Camp B, Vanderkerken K. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 2001 13 3534-3540
32. Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 2005 5 618-625
33. Chirgwin JM, Guise TA. Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr 2000 2 159-178
34. Fisher G, Skillern PG. Hypercalcemia due to hypervitaminosis A. JAMA 1974 227 1413-1414
35. Mugishima H, Chin M, Suga M, Schichino H, Ryo N, Nakamura M, Harada K. Hypercalcemia induced by 13 cis-retinoic acid in patients with neuroblastoma. Pediatr Int 2008 50 235-237
36. Lawrence JA, Adamson PC, Caruso R, Chow C, Kleiner D, Murphy RF, Venzon DJ, Shovlin M, Noone M, Merino M, Cowan KH, Kaiser M, OShaughnessy J, Zujewski J, Phase I. clinical trial of alitretinoin and tamoxifen in breast cancer patients: toxicity, pharmacokinetic, and biomarker evaluations. J Clin Oncol 2001 19 2754-2763
37. Bergman SM, OMailia J, Krane NK, Wallin JD. Vitamin-A-induced hypercalcemia: response to corticosteroids. Nephron 1988 50 362-364
38. Saunders MP, Salisbury AJ, OByrne KJ, Long L, Whitehouse RM, Talbot DC, Mawer EB, Harris AL. A novel cyclic adenosine monophosphate analog induces hypercalcemia via production of 1,25-dihydroxyvitamin D in patients with solid tumors. J Clin Endocrinol Metab 1997 82 4044-4048
39. Kawa S, Yoshizawa K, Nikaido T, Kiyosawa K. Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D3, maxacalcitol, on the proliferation of pancreatic cancer cell lines. J Steroid Biochem Mol Biol 2005 97 173-177
40. Morony S, Warmington K, Adamu S, Asuncion F, Geng Z, Grisanti M, Tan HL, Capparelli C, Starnes C, Weimann B, Dunstan CR, Kostenuik PJ. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy. Endocrin logy 2005 146 3235-3243
41. Zhang X, Jiang F, Li P, Li C, Ma Q, Nicosia SV, Bai W. Growth suppression of ovarian cancer xenografts in nude mice by vitamin D analogue EB108. Clin Cancer Res 2005 11 323-328
42. Kumagai T, OKelly J, Said JW, Koeffler HP. Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. J Natl Cancer Inst 2003 95 896-905
43. Funato K, Miyazawa K, Yaguchi M, Gotoh A, Ohyashiki K. Combination of 22-oxa-1,25-dihydroxyvitamin D(3), a vitamin D(3) derivative, with vitamin K(2) (VK2) synergistically enhances cell differentiation but suppresses VK2-inducing apoptosis in HL-60 cells. Leukemia 2002 16 1519-1527
44. Hansen CM, Mäenpää PH. EB 1089, a novel vitamin D analog with strong antiproliferative and differentiation-inducing effects on target cells. Biochem Pharmacol 1997 54 1173-1179 (Review)
45. Wang X, Gardner JP, Kheir A, Uskokovic MR, Studzinski GP. Synergistic induction of HL60 cell differentiation by ketoconazole and 1-desoxy analogues of vitamin D. J Natl Cancer Inst 1997 89 1199-1206
46. Donnelly J, Hackler RH, Bunts RC. Present urologic status of the World War II paraplegic: 25-year followup. Camparison with status of the 20-year Korean War paraplegic and 5-year Vietnam paraplegic. J Urol 1972 108 558-562
47. Hansen MF, Seton M, Merchant A. Osteosarcoma in Paget's disease of bone. J Bone Miner Res 2006 21 (Suppl 2) 58-63
48. Hallengren B, Spjuth J, Dymling JF. Hypercalcaemia induced by increased thyroxine substitution in a patient treated with dihydrotachysterol. Acta Endocrinol (Copenh) 1984 10 28-30
49. Meythaler JM, Tuel SM, Cross LL. Successful treatment of immobilization hypercalcemia using calcitonin and etidronate. Arch Phys Med Rehabil 1993 74 316-319
50. Kaul S, Sockalosky JJ. Human synthetic calcitonin therapy for hypercalcemia of immobilization. J Pediatr 1995 126 825-827
51. Chen JD, Morrison C, Zhang C, Kahnoski K, Carpten JD, Teh BT. Hyperparathyroidism-jaw tumour syndrome. 2003 253 634-642
52. Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, Farnebo LO, Larsson C, Arnold A. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 2003 349 1722-1729
53. Agha A, Carpenter R, Bhattacharya S, Edmonson SJ, Carlsen E, Monson JP. Parathyroid carcinoma in multiple endocrine neoplasia type 1 (MEN1) syndrome: two case reports of an unrecognised entity. J Endocrinol Invest 2007 30 145-149
54. Nussbaum SR, Gaz RD, Arnold A. Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone. N Engl J Med 1990 323 1324-1328
55. Yoshimoto K, Yamasaki R, Sakai H, Tezuka U, Takahashi M, Iizuka M, Sekiya T, Saito S. Ectopic production of parathyroid hormone by small cell lung cancer in a patient with hypercalcemia. J Clin Endocrinol Metab 1989 68 976-981
56. Rizzoli R, Pache JC, Didierjean L, Bürger A, Bonjour JP. A thymoma as a cause of true ectopic hyperparathyroidism. J Clin Endocrinol Metab 1994 79 912-915
57. Strewler GJ, Budayr AA, Clark OH, Nissenson RA. Production of parathyroid hormone by a malignant nonparathyroid tumor in a hypercalcemic patient. J Clin Endocrinol Metab 1993 1373-1375
58. Strodel WE, Thompson NW, Eckhauser FE, Knol JA. Malignancy and concomitant primary hyperparathyroidism. J Surg Oncol 1988 37 10-12
59. Stanaway SE, Wilding JP. Hypercalcaemia of hypoadrenal crisis mistaken for hypercalcaemia of malignancy in a patient with known bone metastases: a case report. Eur J Intern Med 2000 11 348-350
60. Nelson KA, Walsh D, Abdullah O, McDonnell F, Homsi J, Komurcu S, LeGrand SB, Zhukovsky DS. Common complications of advanced cancer. Semin Oncol 2000 27 34-44
61. Hotta M, Sato K, Shibasaki T, Demura H. Hypercalcemia in an euthyroid patient with secondary hypoadrenalism and diabetes insipidus due to hypothalamic tumor. Endocr J 1998 45 773-778
62. Gesundheit N, Petrick PA, Nissim M, Dahlberg PA, Doppman JL, Emerson CH, Braverman LE, Oldfield EH, Weintraub BD. Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of nine patients. Ann Intern Med 1989 11 827-835
63. Salvatori M, Saletnich I, Rufini V, Dottorini ME, Corsello SM, Troncone L, Shapiro B. Severe thyrotoxicosis due to functioning pulmonary metastases of well-differentiated thyroid cancer. J Nucl Med 1998 39 1202-1207
64. Skrabanek P. Catecholamines cause the hypercalciuria and hypercalcaemia in phaeochromocytoma and in hyperthyroidism. Med Hypotheses 1977 3 59-62
65. Ueda M, Inaba M, Tahara H, Imanishi Y, Goto H, Nishizawa Y. Hypercalcemia in a patient with primary hyperparathyroidism and acromegaly: distinct roles of growth hormone and parathyroid hormone in the development of hypercalcemia. Intern Med 2005 44 307-310
66. Koo WS, Jeon DS, Ahn SJ, Kim YS, Yoon YS, Bang BK. Calcium-free hemodialysis for the management of hypercalcemia. Nephron 1996 72 424-428
67. Vernava AM, ONeal LW, Palermo V. Lethal hyperparathyroid crisis: hazards of phosphate administration. Surgery 1987 102 941-948
68. Berenson JR, Lipton A. Bisphosphonates in the treatment of malignant bone disease. Annu Rev Med 1999 50 237-248
69. Zolendronate (Zometa). Med Lett Drugs Ther 2001 43 110-111
70. Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, Yunus F, Bell R, Body J, Quebe-Fehling E, Seaman J. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001 19 558-567
71. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein M, Coleman RE, Reitsma DJ, Seaman JJ, Chen BL, Ambros Y. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001 7 377-387
72. Markowitz GS, Fine PL, Stack JI, Kunis CL, Radhakrishnan J, Palecki W, Park J, Nasr SH, Hoh S, Siegel DS, DAgati VD. Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 2003 64 281-289
73. Machado CE, Flombaum CD. Safety of pamidronate in patients with renal failure and hypercalcemia. Clin Nephrol 1996 45 175-179
74. Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, DAgati VD. Collapsing focal segmental glomerulosclerosis ollowing treatment with high-dose pamidronate. J Am Soc Nephrol 2001 12 1164-1172
75. th ed Philadelphia, PA: Lippincott Williams & Wilkins 2007 696-699
76. Leyland-Jones B. Treating cancer-related hypercalcemia with gallium nitrate. J Support Oncol 2004 2 509-516 discussion 516520
77. Chitambar CR. Gallium nitrate revisited. Semin Oncol 2003 30 (2 Suppl 5) 1-4
78. Cvitkovic F, Armand JP, Tubiana-Hulin M, Rossi JF, Warrell RP Jr. Randomized, double-blind, phase II trial of gallium nitrate compared with pamidronate for acute control of cancer-related hypercalcemia. Cancer J 2006 12 47-53
79. Edelson GW, Talpos GB, Bone HG. Hypercalcemia associated with Wegener's granulomatosis and hyperparathyroidism: etiology and management. Am J Nephrol 1993 275-277
80. OLeary TJ, Jones G, Yip A, Lohnes D, Cohanim M, Yendt ER. The effects of chloroquine on serum 1,25-dihydroxyvitamin D and calcium etabolism in sarcoidosis. N Engl J Med 1986 315 727-730
81. Barre PE, Gascon-Barré M, Meakins JL, Goltzman D. Hydroxychloroquine treatment of hypercalcemia in a patient with sarcoidosis undergoing hemodialysis. Am J Med 1987 82 1259-1262
82. Adams JS, Kantorovich V. Inability of short-term, low-dose hydroxychloroquine to resolve vitamin D-mediated hypercalcemia in patients with B-cell lymphoma. J Clin Endocrinol Metab 1999 84 799-801
83. Nemeth EF. Pharmacological regulation of parathyroid hormone secretion. Curr Pharm Des 2002 8 2077-2087
84. Nemeth EF, Fox J. Calcimimetic compounds: A direct approach to controlling plasma levels of parathyroid hormone in hyperparathyroidism. Trends Endocrinol Metab 1999 10 66-71
85. Collins MT, Skarulis MC, Bilezikian JP, Silverberg SJ, Spiegel AM, Marx SJ. Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent. J Clin Endocrinol Metab 1998 83 1083-1088
86. Betea D, Bradwell AR, Harvey TC, Mead GP, Schmidt-Gayk H, Ghaye B, Daly AF, Beckers A. Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma. J Clin Endocrinol Metab 2004 89 3413-3420
87. Sato K, Onuma E, Yocum RC, Ogata E. Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. Semin Oncol 2003 30 (5 Suppl 16) 167-173
88. Morony S, Warmington K, Adamu S, Asuncion F, Geng Z, Grisanti M, Tan HL, Capparelli C, Starnes C, Weimann B, Dunstan CR, Kostenuik PJ. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared to bisphosphonates in two models of humoral hypercalcemia of malignancy. Endocrinology 2005 146 3235-3243
89. Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 2005 5 618-625
90. Rifkin WD. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006 354 2390-2391