Part of “CHAPTER 52 – PARATHYROID HORMONE-RELATED PROTEIN“

Patients with humoral hypercalcemia of malignancy as well as normal persons infused with aminoterminal fragments of PTHrP57,74 and animals treated with synthetic PTHrP show many of the hallmark effects of excess PTH, such as hypercalcemia, hypophosphatemia, hyperphosphaturia, elevated nephrogenous cAMP levels, and stimulation of osteoclastic bone resorption. PTHrP levels and calcium in plasma are positively correlated in patients with humoral hypercalcemia of malignancy, as are PTHrP levels and urinary cAMP concentrations.16 Furthermore, the infusion of antibodies against PTHrP is able to reverse hypercalcemia and other manifestations in experimental humoral hypercalcemia of malignancy, including models in which human tumor cells produce hypercalcemia in nude mice.75,76 Therefore, not only is PTHrP capable of producing hypercalcemia, but also secretion of PTHrP is necessary to develop hypercalcemia in such models.