Parathyroid Hormone Related Peptide Elevations in Normocalcemic Adults

Abstract

Abstract Introduction/Objective Elevated parathyroid hormone-related peptide (PTHrP) is a biomarker often associated with hypercalcemia of malignancy. However, elevations of PTHrP can be seen in non-malignant patients with normal calcium status, notably renal failure. We investigate whether a LC-MS/MS test that specifically measures a peptide in the middle region of PTHrP fragments is immune to false elevations of PTHrP. Furthermore, we examine if PTHrP/PTH ratio or renal status can be used to further characterize PTHrP elevations in a cohort of normocalcemic patients. Methods/Case Report We conducted a retrospective study on adult patients that had at least one PTHrP laboratory test (i.e., ARUP PTHrP by LC-MS/MS) within the past 10 years (01/01/2011 to 04/29/2021) at a large academic center. We further stratified this cohort by demographics and additional laboratory markers including calcium status, parathyroid hormone (PTH) (i.e., by Siemens Centaur assay (Malvern, PA)), renal status, and known malignancies. Results (if a Case Study enter NA) We identified a total of 941 patients (585 female and 356 male). 33% of patients (30% [70/233] female and 36% [84/236] male) with elevated PTHrP were normocalcemic (i.e., did not have an elevation in calcium, ionized calcium, or diagnosis of hypercalcemia). 95% (21/22) of normocalcemic males and 100% (17/17) of normocalcemic females with an elevated PTHrP and elevated PTH had a PTHrP/PTH ratio below the normal sex specific reference ranges of 1.07 and 1.86, respectively. A subset of normocalcemic patients with elevated PTHrP had an estimated glomerular filtration rate (eGFR) recorded. Of these patients, 100% (58/58) of females and 94% (65/59) of males had an eGFR below 90 mL/min/1.73 m2 had an eGFR less than 30 mL/min/1.73 m2. and 50% (29/58) of females and 38% (26/69) of males Conclusion Our study supports the hypothesis that elevated PTHrP in the setting of normal calcium may occur due to renal insufficiency.