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Hypercalcemia

In the June 2008 issue of Canadian Family Physician, Dr O’Brien provides a concise and practical review of the treatment of nausea and vomiting in palliative care patients.¹ Still, I would like to take an opportunity to clarify and expand on 2 statements that were made on the topic of hypercalcemia.

First, "Hypercalcemia should be anticipated in patients with bone metastases." Hypercalcemia of malignancy (HCM) occurs in patients with or without osteolytic bone metastases.² In particular, many tumours that frequently develop bone metastases (prostate, small cell lung, and colorectal cancer) are rarely associated with HCM.³

Anticipating HCM involves taking into account not only the presence of bone metastases, but also the primary tumour location and histology. Breast, lung, and head or neck cancers are common primary tumour locations and squamous cell and adenocarcinoma are common histologic subtypes.⁴ Of the hematologic malignancies, multiple myeloma is frequently associated with HCM.⁵

Hypercalcemia of malignancy is broadly divided into 2 categories: humoral hypercalcemia of malignancy and local osteolytic hypercalcemia. The former refers to the paraneoplastic release of humoral factors, mainly parathyroid hormone-related peptide, whereas local osteolytic hypercalcemia refers to the local destruction of bone by tumour with calcium release. There might be considerable overlap between these 2 mechanisms in the pathogenesis of HCM.⁶

Second, "Hypercalcemia can be corrected with saline, diuretics, and bisphosphonates." Since their introduction, parenteral bisphosphonates have become the mainstay of treatment for HCM. As before, copious hydration for volume reexpansion is crucial. With respect to loop diuretics, despite their ability to promote calciuresis, they should be used with caution because of the risk of recurrent hypovolemia and metabolic abnormality.⁶ If diuretics are utilized, ensure the patient is fully hydrated and avoid thiazide diuretics, which could worsen hypercalcemia.⁷

References

1. O’Brien C. Nausea and vomiting. Can Fam Physician 2008;54:861–3.[Free Full Text]
2. Francini G, Petrioli R, Maioli E, Gonnelli S, Marsili S, Aquino A, et al. Hypercalcemia in breast cancer. Clin Exp Metastasis 1993;11(5):359–67.[Medline]
3. Major P. The use of zoledronic acid, a novel, highly potent bisphosphonate, for the treatment of hypercalcemia of malignancy. Oncologist 2002;7(6):481–91.[Abstract/Free Full Text]
4. Penel N, Dewas S, Doutrelant P, Clisant S, Yazdanpanah Y, Adenis A. Cancerassociated hypercalcemia treated with intravenous diphosphonates: a survival and prognostic factor analysis. Support Care Cancer 2008;16(4):387–92Epub 2007 Aug 21.[Medline]
5. Desikan R, Jagannath S, Richardson P, Munshi N. Multiple myeloma and other plasma cell dyscrasias. In: Pazdur R, Coia LR, Hoskins WJ, Lawrence DW, editors. Cancer management: a multidisciplinary approach. New York, NY: CMP Healthcare Media; 2004. p. 729.
6. Ernst SD, Wolch G. Hypercalcemia. In: Bruera E, Higginson I, Ripamonti C, von Gunten C, editors. Textbook of palliative medicine. London, Engl: Hodder Arnold; 2006. p. 799–807.
7. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med 2005;352(4):373–9.[Free Full Text]

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