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Highlights & Basics
- Hypercalcemia of malignancy can result from: humoral hypercalcemia of malignancy (characterized by tumor secretion of parathyroid hormone-related peptide [PTHrP]); local osteolytic hypercalcemia (characterized by local release of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and function); calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcemia (characterized by autonomous production of calcitriol [(1,25-dihydroxyvitamin D)] by lymphoma cells); and ectopic hyperparathyroidism (characterized by tumor production of parathyroid hormone [PTH]), which is very rare.
- Pharmacologic therapy can transiently improve hypercalcemia. However, sustained maintenance of normocalcemia requires eradication of underlying malignancy.
- Treatment options include intravenous bisphosphonates, denosumab, calcitonin, glucocorticoids (for calcitriol [1,25-dihydroxyvitamin D]-mediated hypercalcemia), and calcimimetics (for ectopic PTH production).
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History & Exam
Key Factors
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Definition
Epidemiology
Etiology
Pathophysiology
Images
CT chest showing compression fracture of multiple vertebral bodies in a child presenting with acute lymphoblastic leukemia. Biochemistry showed hypercalcemia with a suppressed parathyroid hormone level
Whole body planar images suggestive of skeletal infiltration in a child with acute lymphoblastic leukemia showing areas of abnormal increased uptake. Biochemistry showed hypercalcemia with a suppressed parathyroid hormone level
Citations
Cancer Institute NSW. Hypercalcaemia of malignancy (HCM). Jul 2019 [internet publication].[Full Text]
Guise TA, Wysolmerski JJ. Cancer-associated hypercalcemia. N Engl J Med. 2022 Apr 14;386(15):1443-51.[Abstract]
Horwitz MJ. Chapter 84: Non-parathyroid hypercalcemia. In: Bilezikian JP, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. Washington, DC: American Society of Bone and Mineral Research; 2018:639-45.
El-Hajj Fuleihan G, Clines GA, Hu MI, et al. Treatment of hypercalcemia of malignancy in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2023 Feb 15;108(3):507-28.[Abstract][Full Text]
Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9.[Abstract]
Alberta Provincial Tumour Council. Oncologic emergencies: a guide for family physicians. Sep 2014 [internet publication].[Full Text]
Society for Endocrinology. Emergency management of acute hypocalcaemia in adult patients. Sep 2016 [internet publication].[Full Text]
Horwitz MJ, Hodak SP, Steward AF. Non-parathyroid hypercalcemia. In: Rosen CJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 8th ed. Washington, DC: American Society of Bone and Mineral Research; 2013:562-71.
Major P, Lortholary A, Hon J, et al. 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 Jan 15;19(2):558-67.[Abstract]
1. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9.[Abstract]
2. Cancer Institute NSW. Hypercalcaemia of malignancy (HCM). Jul 2019 [internet publication].[Full Text]
3. Lindner G, Felber R, Schwarz C, et al. Hypercalcemia in the ED: prevalence, etiology, and outcome. Am J Emerg Med. 2013 Apr;31(4):657-60.[Abstract]
4. Guise TA, Wysolmerski JJ. Cancer-associated hypercalcemia. N Engl J Med. 2022 Apr 14;386(15):1443-51.[Abstract]
5. Horwitz MJ. Chapter 84: Non-parathyroid hypercalcemia. In: Bilezikian JP, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. Washington, DC: American Society of Bone and Mineral Research; 2018:639-45.
6. El-Hajj Fuleihan G, Clines GA, Hu MI, et al. Treatment of hypercalcemia of malignancy in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2023 Feb 15;108(3):507-28.[Abstract][Full Text]
7. Walker MD, Shane E. Hypercalcemia: a review. JAMA. 2022 Oct 25;328(16):1624-36.[Abstract]
8. Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. 2003 May 1;67(9):1959-66.[Abstract][Full Text]
9. US National Cancer Institute: cancer therapy evaluation program. Common terminology criteria for adverse events (CTCAE) v5.0. Nov 2017 [internet publication].[Full Text]
10. Alberta Provincial Tumour Council. Oncologic emergencies. Feb 2022 [internet publication].[Full Text]
11. Strewler GJ, Budayr AA, Clark OH, et al. Production of parathyroid hormone by a malignant nonparathyroid tumor in a hypercalcemic patient. J Clin Endocrinol Metab. 1993 May;76(5):1373-5.[Abstract]
12. VanHouten JN, Yu N, Rimm D, et al. Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene. J Clin Endocrinol Metab. 2006 Feb;91(2):580-3.[Abstract][Full Text]
13. National Institute for Health and Care Excellence. Clinical knowledge summaries: hypercalcaemia. Aug 2019 [internet publication].[Full Text]
14. Fritchie K, Zedek D, Grenache DG. The clinical utility of parathyroid hormone-related peptide in the assessment of hypercalcemia. Clin Chim Acta. 2009 Apr;402(1-2):146-9.[Abstract]
15. Szymanski JJ, Otrock ZK, Patel KK, et al. Incidence of humoral hypercalcemia of malignancy among hypercalcemic patients with cancer. Clin Chim Acta. 2016 Jan 30;453:190-3.[Abstract]
16. Burtis WJ, Brady TG, Orloff JJ, et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med. 1990 Apr 19;322(16):1106-12.[Abstract][Full Text]
17. Lorenzo-Pouso AI, Pérez-Sayáns M, García A, et al. Vitamin D supplementation: hypothetical effect on medication-related osteonecrosis of the jaw. Med Hypotheses. 2018 Jul;116:79-83.[Abstract]
18. Bedogni A, Bettini G, Bedogni G, et al. Is vitamin D deficiency a risk factor for osteonecrosis of the jaw in patients with cancer? A matched case-control study. J Craniomaxillofac Surg. 2019 Aug;47(8):1203-8.[Abstract]
19. Daga N, Joseph F. Denosumab-induced severe hypocalcaemia in a patient with vitamin D deficiency. BMJ Case Rep. 2020 Aug 26;13(8):e234508.[Abstract][Full Text]
20. Räkel A, Boucher A, Ste-Marie L. Role of zoledronic acid in the prevention and treatment of osteoporosis. Clin Interv Aging. 2011 Mar 28;6:89-99.[Abstract][Full Text]
21. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9.[Abstract]
22. Cancer Institute NSW. Hypercalcaemia of malignancy (HCM). Jul 2019 [internet publication].[Full Text]
23. Alberta Provincial Tumour Council. Oncologic emergencies: a guide for family physicians. Sep 2014 [internet publication].[Full Text]
24. Milanesi A, Yu R, Geller SA, et al. Concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with multiple endocrine neoplasia type 1. Pancreas. 2011 May;40(4):634-7.[Abstract]
25. Society for Endocrinology. Emergency management of acute hypocalcaemia in adult patients. Sep 2016 [internet publication].[Full Text]
26. Body JJ, Bartl R, Burckhardt P, et al. Current use of bisphosphonates in oncology. International Bone and Cancer Study Group. J Clin Oncol. 1998 Dec;16(12):3890-9.[Abstract]
27. Major P, Lortholary A, Hon J, et al. 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 Jan 15;19(2):558-67.[Abstract]
28. Medicines and Healthcare products Regulatory Agency. Denosumab (Xgeva) for advanced malignancies involving bone: study data show new primary malignancies reported more frequently compared to zoledronate. Jun 2018 [internet publication].[Full Text]
29. Ljunghall S. Use of clodronate and calcitonin in hypercalcemia due to malignancy. Recent Results Cancer Res. 1989;116:40-5.[Abstract]
30. Chevallier B, Peyron R, Basuyau JP, et al. Human calcitonin in neoplastic hypercalcemia. Results of a prospective randomized trial [in French]. Presse Med. 1988 Dec 17;17(45):2375-7.[Abstract]
31. Wisneski LA. Salmon calcitonin in the acute management of hypercalcemia. Calcif Tissue Int. 1990;46 Suppl:S26-30.[Abstract]
32. Koo WS, Jeon DS, Ahn SJ, et al. Calcium-free hemodialysis for the management of hypercalcemia. Nephron. 1996;72(3):424-8.[Abstract]
33. Bech A, de Boer H. Denosumab for tumor-induced hypercalcemia complicated by renal failure. Ann Intern Med. 2012 Jun 19;156(12):906-7.[Abstract]
34. 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 Nov 8;323(19):1324-8.[Abstract][Full Text]
35. Binstock ML, Mundy GR. Effect of calcitonin and glutocorticoids in combination on the hypercalcemia of malignancy. Ann Intern Med. 1980 Aug;93(2):269-72.[Abstract]
36. Horwitz MJ, Hodak SP, Steward AF. Non-parathyroid hypercalcemia. In: Rosen CJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 8th ed. Washington, DC: American Society of Bone and Mineral Research; 2013:562-71.
37. Major P, Lortholary A, Hon J, et al. 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 Jan 15;19(2):558-67.[Abstract]
