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

Amer A. Budayr, MD; Robert A. Nissenson, PhD; Robert F. Klein, MD; K.K. Pun, MD; Orlo H. Clark, MD; Dinh Diep, BS; Claude D. Arnaud, MD; and Gordon J. Strewler, MD
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Grant Support: Supported in part by the Geisinger Foundation, by NIH grants 5 R01 CA34738, 5 R01 DK21614, and 2 R01 DK35323, and by funds from the Medical Research Service of the Veterans Administration.

Requests for Reprints: Gordon J. Strewler, MD, Endocrine Unit (111N), Veterans Administration Medical Center, 4150 Clement Street, San Francisco, CA 94121.

Current Author Addresses: Drs. Budayr, Nissenson, and Strewler, and Mr. Diep: Endocrine Unit (111N), Veterans Administration Medical Center, 4150 Clement Street, San Francisco, CA 94121.

Dr. Klein: Department of Endocrinology (13-41), Geisinger Medical Center, Danville, PA 17822.

Dr. Pun: Department of Medicine, University of Hong Kong, Pokfulam Road, Hong Kong.

Dr. Clark: Surgical Section (112), Veterans Administration Medical Center, 4150 Clement Street, San Francisco, CA 94121.

Dr. Arnaud: Department of Gerontology, University of California at San Francisco, 1710 Scott Street, San Francisco, CA 94120.

©1989 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1989;111(10):807-812. doi:10.7326/0003-4819-111-10-807
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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± 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. Measurement of iPLP should be useful in the differential diagnosis of hypercalcemia.





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