PTHLH and Hypercalcemia: There are three major mechanisms [10–12] by which hypercalcemia of malignancy can occur: osteolytic metastases with local release of cytokines (including osteoclast activating factors); tumor secretion of parathyroid hormone-related protein (PTHrP); and tumor production of 1,25-dihydroxyvitamin D (calcitriol).