Evidence map›Paper›PMID 40662114›Full record

ReviewJournal of the Endocrine Society2025

Hypercalcemia of Malignancy: Mechanisms and Therapeutic Implications of Concurrently Elevated PTHrP and Calcitriol.

Marisa L Kometas, Naim M Maalouf

Abstract readReview
In one paragraph

Review in Journal of the Endocrine Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Marisa L KometasDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8885, USA.ORCID https://orcid.org/0000-0002-4292-9497
Naim M MaaloufDivision of Endocrinology, Department of Internal Medicine, and Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-8885, USA.ORCID https://orcid.org/0000-0002-0997-283X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Context: Although initially considered rare and associated with solid tumors, concurrent elevations in PTH-related peptide (PTHrP) and calcitriol have been increasingly detected in hypercalcemic patients with a variety of solid and hematologic malignancies. This review discusses the prevalence and pathophysiology and reevaluates the diagnostic and therapeutic implications of PTHrP and calcitriol co-mediated hypercalcemia of malignancy (HCM). Evidence Acquisition: We searched PubMed using multiple combinations of "hypercalcemia of malignancy," PTHrP," "calcitriol," "combined causes," and "concurrent etiologies" and cross-referenced retrieved articles to identify 2 retrospective chart reviews and 17 HCM cases associated with concurrent elevations in PTHrP and calcitriol. Given the scarcity of articles pertaining to co-mediated cases, we contrasted these with literature regarding the pathophysiology, diagnosis, and treatment of isolated humoral and calcitriol-mediated HCM. Evidence Synthesis: The true prevalence of concomitant PTHrP and calcitriol elevations is difficult to determine since these levels are seldom measured simultaneously when evaluating PTH-independent hypercalcemia and vary with tumor type. Malignant tissue is generally considered the source of PTHrP, but the source of calcitriol and the impact of PTHrP on calcitriol synthesis remain controversial. Although most reports suggest that co-mediated hypercalcemia is refractory to antiresorptive and glucocorticoid therapies, long-lasting resolution is associated with cancer remission. Conclusion: Registry-based studies involving cohorts with thorough diagnostic evaluations and randomized control trials are indicated to clarify the prevalence and optimal approach to the management of PTHrP and calcitriol co-mediated HCM. Although IV bisphosphonates and glucocorticoids should be used to alleviate symptomatic hypercalcemia, cancer-targeted therapy is integral to prevent recurrence.

Indexed as

calcitriolhypercalcemia of malignancyPTHrP

Identifiers

PMID40662114
PMCPMC12257092

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.