Hypercalcaemia 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 aetiology of hypercalcaemia 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
Humoral hypercalcaemia of malignancy (parathyroid hormone-related peptide [PTHrP]-mediated) is believed to account for 80% of cases (however, retrospective studies report elevated serum PTHrP levels in <40% of patients).[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
[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.
http://www.ncbi.nlm.nih.gov/pubmed/19168044?tool=bestpractice.com
[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.
http://www.ncbi.nlm.nih.gov/pubmed/26706788?tool=bestpractice.com
[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.
https://www.nejm.org/doi/full/10.1056/NEJM199004193221603
http://www.ncbi.nlm.nih.gov/pubmed/2320080?tool=bestpractice.com
Tumours associated with humoral hypercalcaemia include squamous cell cancer, renal cancer, ovarian cancer, endometrial cancer, breast cancer, and human T-lymphotrophic virus-associated lymphoma.[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
[10]Alberta Provincial Tumour Council. Oncologic emergencies. Feb 2022 [internet publication].
https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-oncologic-emergencies.pdf
Local osteolytic hypercalcaemia (local production of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and activity) accounts for 20% of cases, with typical tumours including breast cancer, multiple myeloma, and lymphoma.[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
[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.[10]Alberta Provincial Tumour Council. Oncologic emergencies. Feb 2022 [internet publication].
https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-oncologic-emergencies.pdf
Hypercalcaemia mediated by increased calcitriol (1,25-dihydroxyvitamin D) synthesis or ectopic parathyroid hormone secretion accounts for <1% of cases.[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
[10]Alberta Provincial Tumour Council. Oncologic emergencies. Feb 2022 [internet publication].
https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-oncologic-emergencies.pdf