Parathyroid Hormone-Related Peptide, Plasma (LAB704)

Humoral Hypercalcemia of Malignancy is a common cause of elevated serum calcium concentrations in patients with cancer. Secretion of this peptide by tumor cells leads to increases in bone resorption, which may outpace renal clearance, leading to marked hypercalcemia in the serum. Given this pathophysiology, PTH concentrations should be suppressed, while total calcium is elevated.

In work by Szymanski et al., a PTH threshold of > 21 pg/mL or a serum calcium < 8.3 mg/dL was found to have no diagnostic utility in patients at Barnes-Jewish Hospital. As such, we recommend that testing for PTHrP be reserved for patients with a recent intact PTH concentration below 50 pg/mL.

• PTHrP testing in the work-up of patients without a known malignancy or suppression of PTH has a very low pre-test probability, which increases the risk of false positives, adds to inefficient healthcare spending, and may cause anxiety-provoking and unnecessary cancer workups.
• Benign conditions associated with elevations in PTHrP include; pregnancy and lactation, renal failure (C-terminal testing only), systemic lupus erythematosus, and heterophile antibodies.

• PTHrP testing should only be pursued when serum calcium is elevated and PTH is < 50 pg/mL.
• Not all elevations in PTHrP indicate malignancy, nor is all hypercalcemia in patients with malignancy related to PTHrP secretion.

1. Mirrakhimov AE. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. N Am J Med Sci. 2015 Nov;7(11):483-93. doi: 10.4103/1947-2714.170600. PMID: 26713296; PMCID: PMC4683803.
2. Szymanski JJ, Otrock ZK, Patel KK, Scott MG. Incidence of humoral hypercalcemia of malignancy among hypercalcemic patients with cancer. Clin Chim Acta. 2016 Jan 30;453:190-3. doi: 10.1016/j.cca.2015.12.017. Epub 2015 Dec 17. PMID: 26706788.