SUN-720 LC-MS/MS Measurements of Parathyroid Hormone-Related Protein (PTHrP): Association Between Ca, PTH and PTHrP in Clinical Samples

Abstract

Parathyroid hormone related protein (PTHrP) is involved in intracellular calcium (Ca) regulation and homeostasis. The main clinical utility of PTHrP as a biomarker is to assist with determining the cause of unexplained hypercalcemia (UH). Considering that PTHrP, along with parathyroid hormone (PTH), is involved in Ca homeostasis, we evaluated associations between concentrations of Ca, PTH, PTHrP and age, and the between-sex differences in clinical patient samples. We reviewed historic data on Ca, PTH and PTHrP concentrations measured in routine patient samples (n=2,701) submitted for testing to a large clinical diagnostic laboratory. Among the analysed samples 31.1% were from adults (18-59y), 52.9% from older adults (60-79y) and 16.9% from elderly (>79y). Out of the samples, 60.5% were from women (W) and 39.5% from men (M). PTHrP was measured using a validated LC-MS/MS method; Ca and parathyroid hormone (PTH) were measured using the Cobas 8000 (Roche). The imprecision of all assays was <10%. Reference intervals (RI) for PTHrP were <3.3 pmol/L and <2.2 pmol/L in W and M, respectively; RI for calcium was 8.4–10.2 mg/dL, and for PTH was 15–65 pg/mL. Median (mean) PTHrP concentrations in samples from adults, older adults and elderly were 1.5 (7.9), 2.5 (8.7) and 3.2 (5.3) pmol/L, respectively. Median (mean) concentrations in samples from W and M were 2.4 (6.3) and 2.5 (10.4) pmol/L, respectively. Statistically significant difference in PTHrP concentrations was observed between W and M from adult (p=0.0005) and older adult (p=0.0038) groups; between W from adult and elderly groups (p=0.0113); and between M from older adult and elderly groups (p=0.028). No significant difference among the age groups was observed in concentrations of Ca and PTH. As expected, direct relationship was observed between concentrations of Ca and PTHrP (ρ=0.189, p<0.0001), while inverse relationships were observed between concentrations of Ca and PTH (ρ=-0.393, p<0.0001), and PTH and PTHrP (ρ=-0.226, p<0.0001). Assessment of the distribution of PTHrP concentrations in samples from W (n=472) and M (n=446) with UH (Ca >10.2 mg/dL and PTH< 15 pg/mL), revealed elevated PTHrP concentrations in 35.0% of W and 59.4% of M; with odds ratio for PTHrP as cause of UH of 0.7 and 2.2, in W and M, respectively. Among the study samples, PTHrP concentrations in 29.3% of samples from W and 54.2% of samples form M were above the sex specific RI. The PTHrP positivity rates in adult, older adult and elderly W (M) were 22.1%, 28.2% and 44.2% (41.2%, 58.5% and 70.5%), respectively. We observed higher prevalence of elevated PTHrP concentrations in M than in W, and in older individuals. PTHrP concentrations above the RI were observed in 39.1% of the analyzed samples. Our data suggest that hypercalcemia caused by elevated PTHrP concentrations is more common for pathologic conditions, which have higher prevalence or specific of M.