# Parathyroid hormone-related protein levels and treatment outcomes in hypercalcemia of malignancy: a retrospective cohort study

## TL;DR

High levels of parathyroid hormone-related protein (PTHrP) may make treating hypercalcemia in cancer patients more difficult, according to a study of 159 patients.

## Contribution

This study identifies elevated PTHrP levels as a potential risk factor for treatment resistance in hypercalcemia of malignancy.

## Key findings

- Higher PTHrP levels correlated with smaller decreases in corrected calcium levels after treatment.
- Patients with high PTHrP levels were less likely to achieve a treatment response within two weeks.
- Elevated PTHrP is a potential risk factor for treatment resistance in hypercalcemia of malignancy.

## Abstract

The challenge of managing acute hypercalcemia in patients diagnosed with hypercalcemia of malignancy (HCM) merits further attention. Elevated levels of PTHrP may be a risk factor for treatment resistance in acute hypercalcemia; however, few studies have tested this hypothesis. This study aimed to investigate whether high PTHrP levels represent an independent risk factor that impedes the treatment of acute hypercalcemia. This retrospective cohort study recruited 159 patients aged 20-80 years with diagnosed malignancies who had been hospitalized for hypercalcemia with PTHrP levels above the reference value (1.1 pmol/L). The median (25%-75%) patient age was 69 (61-76) years, and the median PTHrP level was 6.3 (3.3-11.1) pmol/L. The corrected calcium levels decreased from 12.8 mg/dL (11.9-14.1 mg/dL) to 10.6 mg/dL (9.8-11.7 mg/dL) following treatments, such as bisphosphonates and saline solution. Multivariate linear regression analysis showed less significant decreases in the corrected calcium levels as natural logarithm-transformed PTHrP levels increased (β coefficient [95% CI]: 0.569 [0.225-0.914]; p = .001 for Model 3). Multivariate logistic regression analysis showed an association between high natural logarithm-transformed PTHrP levels and lack of treatment response, defined as a corrected calcium level of ≤10.4 mg/dL in the last blood test conducted within 2 wk of treatment initiation (odds ratio [95% CI]: 0.504 [0.312-0.814]; p = .005). Therefore, elevated PTHrP levels are a potential risk factor for treatment resistance in hypercalcemia in HCM patients, complicating management regardless of calcium levels.

Graphical Abstract