Parathyroid hormone–related protein–mediated hypercalcemia of malignancy: insights from a multicenter clinical data warehouse

Abstract

Background/Aims Parathyroid hormone–related protein (PTHrP) is a major mediator of hypercalcemia in patients with malignancy; however, understanding of PTHrP-mediated hypercalcemia remains limited because available evidence has largely been derived from small case series. Methods We retrospectively analyzed electronic medical records from eight hospitals affiliated with The Catholic University of Korea. Adult patients (> 20 years) with confirmed malignancy and albumin-corrected hypercalcemia (≥ 10.5 mg/dL) between 2013 and 2022 were identified and classified as having PTHrP-mediated hypercalcemia (PTHrP > 1.1 pmol/L) or hypercalcemia due to other causes (PTHrP ≤ 1.1 pmol/L). Results Among the 289 patients reported to have PTHrP-mediated hypercalcemia, median age was 66 years (interquartile range [IQR], 59–75) and median plasma PTHrP level was 6.1 pmol/L (IQR, 3.5–11.5). Solid tumors accounted for 86% of cases, while hematologic malignancies accounted for the other 14%. The most common cancer types were lung cancer (30%, n = 87), head and neck cancer (11%, n = 31), and multiple myeloma (8%, n = 24). Median survival after the onset of hypercalcemia was 46 days (95% confidence interval [CI], 36–61) in patients with PTHrP-mediated hypercalcemia. Compared with the 169 patients with hypercalcemia due to other causes, PTHrP-mediated hypercalcemia was associated with a higher risk of mortality after adjustment for age, corrected calcium level, and cancer type (adjusted hazard ratio, 4.0; 95% CI, 2.9–5.4). Conclusions PTHrP-mediated hypercalcemia occurs across a broad spectrum of malignancies and is associated with worse clinical outcomes.