The term “hypercalcemia of malignancy” is routinely used when calcium is elevated and PTH is below normal, and for good reason— this situation is often a result of malignant neoplasia, particularly lymphoma, anal sac adenocarcinoma, or multiple myeloma.  However, many other diseases can fall into this category such as granulomatous disease, hyperthyroidism, vitamin D intoxication, and Addison’s disease.

There are three major mechanisms by which hypercalcemia of malignancy can occur:

  1. osteolytic activity with local release of cytokines (including osteoclast activating factors)
  2. tumor secretion of parathyroid hormone-related protein (PTHrP)
  3. production of 1,25-dihydroxyvitamin D (calcitriol).

When a patient presents with hypercalcemia of unknown origin, a good place to begin is with a calcium and PTH measurement.  If hypercalcemia of malignancy is present, the VDI Calcemia Panel report will plot within the lower red zone:


To rule in/out neoplasia as the reason for hypercalcemia, reflexing to the TK Cancer Panel will provide fast insight if neoplasia is suspect.  If negative, other non-neoplastic causes can be further investigated.