Technical and Clinical Validation of an Immunoradiometric Assay for Circulating Parathyroid Hormone-related Protein

Abstract

Parathyroid hormone-related protein (PTHrP) plays a key role in hypercalcemia of malignancy (HM), particularly in humoral HM (HHM) (1)(2). Serum PTHrP is increased in 47–100% of HM patients (3)(4)(5)(6) and in almost all patients with HHM. In up to two-thirds of hypercalcemic patients with bone metastases, serum PTHrP is increased (5)(7). PTHrP assays may aid in the diagnosis of HHM (8). IRMAs that measure large N-terminal regions appear to be optimal for HM evaluation (9). With the first commercially available IRMA (Nichols Institute), PTHrP concentrations were found to be increased in 40 of 81 (49%) HM patients. Moreover, healthy subjects had detectable values up to 2.6 pmol/L (10), contrary to some reports (5)(8)(11). With an IRMA from Mitsubishi Petrochemical Co (12), PTHrP was increased in all 46 studied patients with hypercalcemia and solid tumors, and most healthy subjects had values <1 pmol/L. However, almost all patients had HHM, and the specificity toward normocalcemic cancer (C.NoCa) patients was not thoroughly investigated. We have evaluated a commercially available PTHrP IRMA. We particularly studied the assay specificity for HM patients compared with normocalcemic patients presenting an active cancer, with patients in complete remission from their cancer, and with patients suffering from osteopenia, osteoporosis, or chronic renal failure (CRF). The first control group included 94 patients (88 women and 6 men), median age 61 years (range, 26–80 years), referred to our bone clinic for a low bone mass or established osteoporosis. The patients were classified (13) as follows: 39 osteopenic (T score at the lumbar spine of −1.78 ± 0.09, mean ± SE); 29 osteoporotic (T score −3.16 ± 0.10); 26 established osteoporosis (low bone mass and presence of one or more fragility fractures). The second control group included …