PARATHYROID HORMONE-RELATED PROTEIN AND RESPONSE TO PAMIDRONATE IN TUMOR-INDUCED HYPERCALCEMIA

To find out if the concentration of parathyroid hormone-related protei n (PTHrP) predicts the response of tumour-inducing hypercalcaemia (TIH ) to pamidronate, we studied 44 patients. Pretreatment measurements of serum PTHrP, calcium and phosphate, nephrogenous cyclic AMP, tubular threshold for calcium and phosphate (TmP), and the presence of bone me tastases were correlated with response to pamidronate. Response was co nsidered good (normal calcium concentration corrected for albumin [CCa ] for > 14 days), or poor (failure of CCa to fall, or a rise above nor mal less-than-or-equal-to 14 days). PTHrP correlated significantly wit h response (good vs poor, p = 0.02). Undetectable PTHrP (< 2 pmol/L) w as associated with a good response in all seven treatments, PTHrP in t he range 2-12 pmol/L was associated with good response in 10 of 14 tre atments, while PTHrP greater-than-or-equal-to 12 pmol/L was associated with a poor response in all 11 treatments. Tubular threshold for calc ium correlated with the fall in CCa by day 6 after treatment (p = 0.02 ). Urinary clearance estimations in poor responders suggested that the re was an incomplete reversal of the renal tubular component of hyperc alcaemia. Serum PTHrP correlates with response to pamidronate in the t reatment of TIH; which may be associated with a renal tubular mechanis m not significantly affected by currently available treatment. Drugs t hat inhibit tubular reabsorption of calcium or PTHrP secretion may hel p in patients who do not respond to pamidronate.