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“Hypercalcemia of Malignancy” may not be due to malignancy

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.