Increased Serum Levels of a Parathyroid Hormone-like Protein in Malignancy-Associated Hypercalcemia

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Abstract
Study Objective: To measure the serum levels of a newly described parathyroid hormone-like protein (PLP), which was isolated from malignant tumors associated with hypercalcemia, and determine whether PLP is a humoral factor in malignancy-associated hypercalcemia. Design: A cross-sectional study of serum levels of PLP using a newly developed radioimmunoassay. Setting: A university-affiliated Veterans Administration hospital in San Francisco, California, a University hospital in Hong Kong, and a private hospital in Danville, Pennsylvania. Patients: Patients with hypercalcemia (calcium > 2.65 mmol/L) and a diagnosis of malignancy were studied. Control groups included normocalcemic patients with malignancy, patients with hyperparathyroidism, and normal subjects. Measurements and Main Results: Serum immunoreactive PLP (iPLP) levels in normal subjects were less than 2.5 pmol eq/L (10 pg/mL), and 68% of subjects had undetectable levels. The serum concentration of iPLP was normal in 15 of 16 hypercalcemic patients with hyperparathyroidism. Serum iPLP was increased (> 2.5 pmol eq/L) in 36 of 65 (55%) patients with malignancy-associated hypercalcemia, with a mean value of 6.1 .+-. 0.9 pmol eq/L (24 pg/mL). In a subgroup of patients with solid tumors, serum iPLP was increased in 30 (71%) of 42 hypercalcemic patients, with a mean value of 6.5 .+-. 0.9 pmol eq/L. Serum iPLP was elevated in only 3 of 23 normocalcemic patients with cancer. In patients with solid malignancies (n = 59), levels of iPLP were positively correlated with the total serum calcium (r = 0.43, P < 0.01). Conclusions: The data indicate a relation between the serum concentration of iPLP and the presence of hypercalcemia in solid malignancies. The results support a role for PLP as a humoral mediator of hypercalcemia in most patients with solid tumors. Measurements of iPLP should be useful in the differential diagnosis of hypercalcemia.