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

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). CONCLUSION: PTHrP-mediated hypercalcemia occurs across a broad spectrum of malignancies and is associated with worse clinical outcomes.