{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T12:00:41Z","timestamp":1781092841519,"version":"3.54.1"},"reference-count":33,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hypercalcemia of malignancy (HCM) is a common complication of advanced cancer. PTH-independent HCM may be mediated through different mechanisms: (1) humoral HCM, caused by the secretion of PTH-related peptide (PTHrP), (2) local osteolysis resulting from metastatic lesions, and (3) calcitriol-mediated hypercalcemia. Calcitriol-mediated HCM in patients with nonlymphomatous solid tumors is thought to be rare.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a retrospective chart review from 2008 to 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 with patients with HCM but without calcitriol elevation. We also aimed to assess mortality and determine if PTHrP and phosphorus levels correlate with calcitriol because both factors may alter calcitriol levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 101 eligible patients, calcitriol was elevated in 45 (45%). PTHrP was elevated in 76% of patients with elevated calcitriol compared with 52% of patients without calcitriol elevation. The mean PTHrP value did not differ between patients with HCM and elevated calcitriol (36.3 \u00b1 22 pg\/mL) and those without calcitriol elevation (37.4 \u00b1 19 pg\/mL). Those with elevated calcitriol levels generally did not respond completely to antiresorptive treatment (80% incomplete response rate), whereas most patients without an elevation in calcitriol responded well to antiresorptive treatment (78% response rate: P &amp;lt; .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 = .14). A weak but significant negative correlation was found between phosphorus and calcitriol (Pearson r = -0.261, P = .016). This correlation was only significant in patients without calcitriol elevation (Pearson r = -0.4, P = .0082). Also, a significant negative correlation was found between PTHrP and phosphorus, again only in patients without calcitriol elevation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>In the setting of HCM, patients with calcitriol elevation are much less likely to respond to antiresorptive therapy than patients without calcitriol elevation. Because 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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz278","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T18:17:29Z","timestamp":1576520249000},"page":"e1115-e1123","source":"Crossref","is-referenced-by-count":32,"title":["Calcitriol Elevation Is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-4171","authenticated-orcid":false,"given":"Tariq","family":"Chukir","sequence":"first","affiliation":[{"name":"Endocrinology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, NewYork-Presbyterian\/Weill Cornell Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Bilezikian","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azeez","family":"Farooki","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"issue":"4","key":"2021122210041971000_CIT0001","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1056\/NEJMcp042806","article-title":"Clinical practice. Hypercalcemia associated with cancer","volume":"352","author":"Stewart","year":"2005","journal-title":"N Engl J Med."},{"issue":"1","key":"2021122210041971000_CIT0002","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1590\/2359-3997000000015","article-title":"Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma","volume":"59","author":"Gomes","year":"2015","journal-title":"Arch Endocrinol Metab."},{"issue":"7","key":"2021122210041971000_CIT0003","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/1097-0142(19871001)60:7<1620::AID-CNCR2820600733>3.0.CO;2-3","article-title":"Distinguishing features of primary hyperparathyroidism in patients with breast cancer","volume":"60","author":"Axelrod","year":"1987","journal-title":"Cancer."},{"issue":"1","key":"2021122210041971000_CIT0004","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/BF02207080","article-title":"Calcium and vitamin D metabolism in granulomatous diseases","volume":"11","author":"Fuss","year":"1992","journal-title":"Clin Rheumatol."},{"issue":"3","key":"2021122210041971000_CIT0005","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1359\/jbmr.2003.18.3.579","article-title":"Vitamin D-mediated hypercalcemia in lymphoma: evidence for hormone production by tumor-adjacent macrophages","volume":"18","author":"Hewison","year":"2003","journal-title":"J Bone Miner Res."},{"issue":"5","key":"2021122210041971000_CIT0006","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1182\/blood.V82.5.1383.1383","article-title":"Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin\u2019s disease and non-Hodgkin\u2019s lymphomas","volume":"82","author":"Seymour","year":"1993","journal-title":"Blood."},{"issue":"10","key":"2021122210041971000_CIT0007","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1210\/jc.2013-2016","article-title":"Calcitriol-mediated hypercalcemia: causes and course in 101 patients","volume":"98","author":"Donovan","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122210041971000_CIT0008","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1210\/er.2016-1070","article-title":"Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment","volume":"37","author":"Tebben","year":"2016","journal-title":"Endocr Rev."},{"issue":"8","key":"2021122210041971000_CIT0009","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1210\/jc.2006-0021","article-title":"Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men","volume":"91","author":"Antoniucci","year":"2006","journal-title":"J Clin Endocrinol Metab."},{"issue":"1-2","key":"2021122210041971000_CIT0010","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.mce.2011.08.030","article-title":"Vitamin D metabolism in the kidney: regulation by phosphorus and fibroblast growth factor 23","volume":"347","author":"Perwad","year":"2011","journal-title":"Mol Cell Endocrinol."},{"issue":"15","key":"2021122210041971000_CIT0011","doi-asserted-by":"crossref","first-page":"7151","DOI":"10.1016\/S0021-9258(18)48217-8","article-title":"Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy","volume":"262","author":"Burtis","year":"1987","journal-title":"J Biol Chem."},{"issue":"5","key":"2021122210041971000_CIT0012","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1210\/jc.2014-4250","article-title":"PTHrP-mediated hypercalcemia: causes and survival in 138 patients","volume":"100","author":"Donovan","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122210041971000_CIT0013","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1681\/ASN.2007090981","article-title":"PTH-related peptide (PTHrP) in hypercalcemia","volume":"19","author":"Mundy","year":"2008","journal-title":"J Am Soc Nephrol."},{"issue":"3","key":"2021122210041971000_CIT0014","first-page":"801","article-title":"Parathyroid hormone-related protein (PTHrP) does not regulate 1,25-dihydroxyvitamin D serum levels in hypercalcemia of malignancy","volume":"76","author":"Schilling","year":"1993","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2021122210041971000_CIT0015","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/jbmr.5650030616","article-title":"Effects of infusion of human parathyroid hormone-related protein-(1-40) in nude mice: histomorphometric and biochemical investigations","volume":"3","author":"Rosol","year":"1988","journal-title":"J Bone Miner Res."},{"issue":"10","key":"2021122210041971000_CIT0016","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1359\/JBMR.050602","article-title":"Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D","volume":"20","author":"Horwitz","year":"2005","journal-title":"J Bone Miner Res."},{"issue":"9","key":"2021122210041971000_CIT0017","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1210\/jc.2014-1001","article-title":"Denosumab for treatment of hypercalcemia of malignancy","volume":"99","author":"Hu","year":"2014","journal-title":"J Clin Endocrinol Metab."},{"issue":"7","key":"2021122210041971000_CIT0018","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/qjmed\/hcq039","article-title":"Medication-induced hypophosphatemia: a review","volume":"103","author":"Liamis","year":"2010","journal-title":"QJM."},{"issue":"1","key":"2021122210041971000_CIT0019","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1053\/j.ackd.2013.05.005","article-title":"Electrolyte disorders associated with cancer","volume":"21","author":"Rosner","year":"2014","journal-title":"Adv Chronic Kidney Dis."},{"key":"2021122210041971000_CIT0020","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2014-206590","article-title":"Tumour-associated osteomalacia and hypoglycaemia in a patient with prostate cancer: is Klotho involved?","volume":"2014","author":"Latifyan","year":"2014","journal-title":"BMJ Case Rep."},{"issue":"3","key":"2021122210041971000_CIT0021","doi-asserted-by":"crossref","first-page":"R53","DOI":"10.1530\/ERC-11-0006","article-title":"Tumor-induced osteomalacia","volume":"18","author":"Chong","year":"2011","journal-title":"Endocr Relat Cancer."},{"issue":"6","key":"2021122210041971000_CIT0022","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1172\/JCI117990","article-title":"Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo","volume":"95","author":"de la Mata","year":"1995","journal-title":"J Clin Invest."},{"issue":"1","key":"2021122210041971000_CIT0023","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1210\/endo.131.1.1319327","article-title":"Inhibition by human interleukin-1 alpha of parathyroid hormone-related peptide effects on renal calcium and phosphorus metabolism in the rat","volume":"131","author":"T\u00f8rring","year":"1992","journal-title":"Endocrinology."},{"issue":"15","key":"2021122210041971000_CIT0024","first-page":"3194","article-title":"Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo","volume":"57","author":"Uy","year":"1997","journal-title":"Cancer Res."},{"issue":"3","key":"2021122210041971000_CIT0025","first-page":"212","article-title":"Resectable bronchogenic carcinoma presenting with hypercalcemia: tumor-associated granulomatous reaction and probable production of 1,25-dihydroxyvitamin D","volume":"12","author":"Akai","year":"1989","journal-title":"Clin Invest Med."},{"issue":"9","key":"2021122210041971000_CIT0026","doi-asserted-by":"crossref","first-page":"633","DOI":"10.7326\/0003-4819-121-9-199411010-00001","article-title":"Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma","volume":"121","author":"Seymour","year":"1994","journal-title":"Ann Intern Med."},{"issue":"9269","key":"2021122210041971000_CIT0027","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0140-6736(00)04831-5","article-title":"25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue","volume":"357","author":"Tangpricha","year":"2001","journal-title":"Lancet."},{"issue":"1","key":"2021122210041971000_CIT0028","first-page":"155","article-title":"Expression of 25-hydroxyvitamin D-1-alpha-hydroxylase, and vitamin D receptor mRNA in normal and malignant breast tissue","volume":"29","author":"McCarthy","year":"2009","journal-title":"Anticancer Res."},{"issue":"5","key":"2021122210041971000_CIT0029","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1172\/JCI45890","article-title":"Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization","volume":"122","author":"Lieben","year":"2012","journal-title":"J Clin Invest."},{"issue":"5","key":"2021122210041971000_CIT0030","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1172\/JCI45890","article-title":"Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization","volume":"122","author":"Lieben","year":"2012","journal-title":"J Clin Invest."},{"issue":"3","key":"2021122210041971000_CIT0031","first-page":"277","article-title":"Ketoconazole for the treatment of refractory hypercalcemic sarcoidosis","volume":"17","author":"Conron","year":"2000","journal-title":"Sarcoidosis Vasc Diffuse Lung Dis."},{"issue":"1","key":"2021122210041971000_CIT0032","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM196601062740101","article-title":"Inorganic phosphate treatment of hypercalcemia of diverse etiologies","volume":"274","author":"Goldsmith","year":"1966","journal-title":"N Engl J Med."},{"issue":"5622","key":"2021122210041971000_CIT0033","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/bmj.4.5622.14","article-title":"Phosphate treatment of hypercalcaemia due to carcinoma","volume":"4","author":"Thalassinos","year":"1968","journal-title":"Br Med J."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgz278\/31551681\/dgz278.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1115\/41863327\/jcem_105_4_e1115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1115\/41863327\/jcem_105_4_e1115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T18:14:26Z","timestamp":1640196866000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/4\/e1115\/5679485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,16]]},"references-count":33,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12,16]]},"published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgz278","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2019,12,16]]}}}