Parathyroid hormone-related protein, parathyroid hormone, and vitamin D inhypercalcemia of malignancy

The pathogenesis of cancer-associated hypercalcemia is not yet completely u nderstood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy , in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1,25(OH)(2)D -3. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1,25(OH)(2)D-3 with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were n ormocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols ), and 1,25(OH)(2)D-3 by radioreceptor assay (Nichols), in plasma in both g roups of cancer patients. Using a logistic regression analysis, we found th at the higher PTHrP in plasma, the higher association with hypercalcemia oc curred in these patients. In addition, the decreased plasma levels of PTH a nd 1,25(OH)(2)D-3 in the majority: of:cancer patients were found to be sign ificantly associated with hypercalcemia. Our results indicate that the comb ined determination of PTH, PTHrP and 1,25(OH)(2)D-3 in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor resp onsible for hypercalcemia in these patients. (C) 2000 Elsevier Science B.V. All rights reserved.