CONTRIBUTION OF PARATHYROID HORMONE-RELATED PEPTIDE TO THE EVALUATIONOF HYPERCALCEMIA

Hypercalcemia of malignancy is due either to local osteolysis at the s ite of bone metastases or to production by the malignancy of parathyro id hormone-related peptide, which shares some of the effects of parath yroid hormone. We used a radioimmunoassay (antiserum specific to the a mino-terminus) to measure serum parathyroid hormone-related peptide le vels in controls (n = 61), chronic renal failure patients (n = 10), pa tients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignan cies (n = 15). We set the upper limit of normal of the parathyroid hor mone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere wi th the assay. Eighteen of the 19 patients with primary hyperparathyroi dism had normal levels. In contrast, 82% of patients with humoral hype rcalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse co rrelation between serum levels of the peptide and phosphorus. Elevatio n of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevat ed parathyroid hormone-related peptide levels. In our overall study po pulation, serum calcium levels were weakly but significantly correlate d with parathyroid hormone-related peptide levels, In conclusion, elev ated parathyroid hormone-related peptide in a patient with hypercalcem ia suggests a malignant disease, Possible causes include epidermoid tu mors but also other tumor types such as a mammary adenocarcinoma with or without bone metastases. The peptide induces hypercalcemia not only by stimulating bone resorption but also by increasing the reabsorptio n of calcium by renal tubules. The latter effect may explain why bisph osphonates, which act only on the bony component, are often only parti ally effective..