Parathyroid-hormone-related peptide in hematologic malignancies.
OBJECTIVE
To determine whether parathyroid-hormone-related peptide (PTHRP) is an important pathogenetic mediator of hypercalcemia in patients with hematologic malignancies.


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.
Kremer
R
R
Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
Shustik
C
C
Tabak
T
T
Papavasiliou
V
V
Goltzman
D
D
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000097:blood; D002118:Calcium / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006689:Hodgkin Disease / Q000097:blood* / Q000473:pathology; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009101:Multiple Myeloma / Q000097:blood*; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D010281:Parathyroid Hormone / Q000097:blood*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000032:analysis*; D008258:Waldenstrom Macroglobulinemia / Q000097:blood*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D002117:Calcitriol; D002118:Calcium