Hypercalcemia of malignancy

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).

Hypercalcemia occurs in 20% to 30% of patients with cancer.[1]Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9. http://www.ncbi.nlm.nih.gov/pubmed/15673803?tool=bestpractice.com [2]Cancer Institute NSW. Hypercalcaemia of malignancy (HCM). Jul 2019 [internet publication]. https://www.eviq.org.au/clinical-resources/oncological-emergencies/486-hypercalcaemia-of-malignancy-hcm Cancer represents the most common etiology of hypercalcemia in the inpatient setting.[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. http://www.ncbi.nlm.nih.gov/pubmed/23246111?tool=bestpractice.com It 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), which is very rare.[4]Guise TA, Wysolmerski JJ. Cancer-associated hypercalcemia. N Engl J Med. 2022 Apr 14;386(15):1443-51. http://www.ncbi.nlm.nih.gov/pubmed/35417639?tool=bestpractice.com ​​[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.