EFFECTS OF TREATMENT OF MALIGNANCY-ASSOCIATED HYPERCALCEMIA ON SERUM PARATHYROID HORMONE-RELATED PROTEIN

Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia. W e conducted this study to examine the effects of treatment with a bisp hosphonate on serum PTHrP. We analyzed 41 episodes of hypercalcemia oc curring in 38 patients: 22 patients received alendronate, and 16 were treated with pamidronate. At baseline, 29 patients had an increased se rum PTHrP (group I) and 9 had low or undetectable levels (group II). T he two groups did not differ significantly in baseline hypercalcemia ( 3.26 versus 3.41 mM) or the response of serum calcium to therapy. Seru m calcium was normalized in 88 % of group I and 70 % of group II patie nts. Lowering of the mean calcium level was not associated with a chan ge in the level of PTHrP in group I patients (40.2 versus 36.7 pgEq/ml ) or group II patients. We also analyzed data on serum PTH and 1,25-(O H)2D in 20 of the patients. Serum PTH rose with treatment in group I p atients (9.7-40.2 pg/ml, p < 0.05), as did the serum 1,25-(OH)2D (19.1 -32.4 pg/ml, p < 0.001). Similarly, treatment of group 11 patients was associated with an increase in serum PTH (9.8-37.2 pg/ml) and serum 1 ,25-(OH)2D (22.9-40.2 pg/ml). The individual increases in 1,25-(OH)2D levels associated with therapy could not be predicted from the level o f PTHrP or the changes in levels of serum calcium or PTH. Our data sho w that effective treatment of malignancy-associated hypercalcemia is n ot associated with a consistent change in serum levels of PTHrP. Thera py is associated with a variable increase in the serum levels of PTH a nd 1,25-(OH)2D.