Raised plasma concentrations of parathyroid hormone related peptide in hypercalcemic multiple myeloma

In order to clarify the pathogenesis of hypercalcemia in multiple myeloma, we measured plasma levels of parathyroid hormone related peptide (PTHrP), tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta), intact PTH and, serum 1,25-dihydroxyvitamin D in fifteen patients of multiple myeloma. We also measured serum levels of inorganic phosphorus (iP) and alkalinephosphatase activity (ALP). No significant differences in iP (3.2 +/- 0.4 vs. 4.0 +/- 2.2 mg/dl), ALP (150 +/- 28 vs. 335 +/- 305 IU/l) 1,25(OH)2 D (31.5 +/- 17.0 vs. 23.3 +/- 11.2 pg/ml) or TNF-alpha (7.8 +/- 2.1 vs. 8.0 +/- 2.0 pg/ml) were observed between normocalcemic and hypercalcemic patients. Plasma iPTH levels in hypercalcemic patients were significantly lower than those in normocalcemic patients (28.5 +/- 9.4 vs. 16.3 +/- 5.6 pg/ml, p = 0.01). Plasma levels of TNF-beta were less than 15.6 pg/ml in all subjects. On the other hand, the frequency of patients with abnormally high plasma levels of PTHrP was significantly greater (2/9 for normocalcemia vs 5/6 for hypercalcemia, chi 2 = 5.20, p = 0.02) in patients with hypercalcemia than in normocalcemic patients. Furthermore, a significant positive relationship between plasma PTHrP levels and corrected serum calcium levels (cCa) was observed using Spearman's correlation analysis by rank in fifteen myeloma cases (rs = 0.66, p = 0.013). These results suggest that PTHrP might be involved in the elevation of serum calcium levels in hypercalcemic myeloma patients. However, a few cases exhibit normocalcemia despite elevated plasma PTHrP levels or hypercalcemia without high plasma PTHrP levels. Therefore, further studies are necessary to elucidate the pathogenesis of hypercalcemia in multiple myeloma.