Purpose: To determine whether parathyroid-hormone-related peptide (PTHRP) is an important pathogenetic mediator of hypercalcemia in patients with hematologic malignancies.
Patients and methods: We conducted a cohort analytic study in 76 consecutive patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease, multiple myeloma, and Waldenstrom's macroglobulinemia, 14 of which were hypercalcemic. Thirty normal subjects served as a control group.
Results: Using the NH2 -terminal radioimmunoassay, PTHRP concentrations in heavy controls were undetectable (<7.5 pmol equivalents of PTHRP [fragment 1-34] per liter). The majority of hypercalcemic patients (8/14) had non-Hodgkin's lymphoma, and 62.5% of these (5/8) had significant elevations of circulating PTHRP concentrations (mean 70.5 +/- 38.5 pmol equivalents of PTHRP per liter) (P <0.01). In non-Hodgkin's lymphoma, 11 of 30 patients with advanced disease (stage IV) had elevated PTHRP concentrations, and of these, 8 of 11 had high-grade pathology. In contrast, only 3 or 21 patients with less advanced disease (stage I to III) had elevated PTHRP concentrations. In 4 NHL patients with less advance PTHRP concentrations sampled prior to cytotoxic chemotherapy, tumor response was associated with a decrease in PTHRP. Concomitant suppression of 1,25(OH)2D3 concentrations was observed in 66% of hypercalcemic patients with non-Hodgkin's lymphoma.
Conclusions: These results suggest that PTHRP may be an important pathogenetic factor in the development of hypercalcemia in hematologic malignancies, notably in non-Hodgkin's lymphoma.