Calcitriol Elevation is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors.

Calcitriol Elevation is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors.:

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Calcitriol Elevation is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors.

J Clin Endocrinol Metab. 2019 Dec 16;:

Authors: Chukir T, Liu Y, Hoffman K, Bilezikian JP, Farooki A

Abstract

BACKGROUND: Hypercalcemia of malignancy (HCM) is a common complication of advanced cancer. Parathyroid hormone (PTH)-independent HCM may be mediated through different mechanisms: 1) humoral HCM, caused by the secretion of parathyroid hormone-related peptide (PTHrP), 2) local osteolysis due to metastatic lesions, and, 3) calcitriol-mediated hypercalcemia. Calcitriol-mediated HCM in patients with non-lymphomatous solid tumors is thought to be rare.

METHODS: We performed a retrospective chart review from 2008-2017 to characterize further patients at our institution with solid tumors who had HCM with concomitant elevations in calcitriol. Patients with PTH dependent hypercalcemia and patients with evidence of granulomatous disease were excluded as were patients with hematologic malignancies. We hypothesized that patients with HCM and elevated calcitriol levels would respond less favorably to treatment with antiresorptive therapy compared to patients with HCM but without calcitriol elevation. We also aimed to assess mortality and determine if PTHrP and phosphorus levels correlate with calcitriol, as both factors may alter calcitriol levels.

RESULTS: Of 101 eligible patients, calcitriol was elevated in 45 (45%). PTHrP was elevated in 76% of patients with elevated calcitriol compared to 52% of patients without calcitriol elevation. The mean PTHrP value did not differ between patients with HCM and elevated calcitriol (36.3 ± 22 pg/mL) and those without calcitriol elevation (37.4 ± 19 pg/mL). Those with elevated calcitriol levels generally did not respond completely to antiresorptive treatment (80% incomplete response rate) while most patients without an elevation in calcitriol responded well to antiresorptive treatment (78% response rate: p <0.001). There was no significant difference in the percentage of patients with metastatic bone disease among the 2 groups (49% vs. 55%, respectively). There was no difference in mortality between the 2 groups (p=0.14). A weak but significant negative correlation was found between phosphorus and calcitriol (Pearson's r = -0.261, p=0.016). This correlation was only significant in patients without calcitriol elevation. (Pearson's r = -0.4, p=0.0082). Also, a significant negative correlation was found between PTHrP and phosphorus, again only in patients without calcitriol elevation.

DISCUSSION: In the setting of HCM, patients with calcitriol elevation are much less likely to respond to antiresorptive therapy than patients without calcitriol elevation. Since calcitriol elevation did not appear to be correlated with hypophosphatemia or elevated PTHrP, it would appear that calcitriol production under these conditions is autonomous, and not subject to normal physiological controls. These observations indicate that calcitriol elevations in patients with HCM have clinical significance.

PMID: 31841590 [PubMed - as supplied by publisher]