{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:48Z","timestamp":1784557068190,"version":"3.55.0"},"reference-count":10,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Human T-cell lymphotropic virus-1 (HTLV-1) causes adult T-cell leukemia and lymphoma (ATLL) and is a rare but important cause of hypercalcemia. A 53-year-old male with HTLV-1-associated myelopathy presented with acute on chronic bilateral lower extremity weakness and numbness. Initial blood work revealed hypercalcemia with corrected calcium of 16.2 mg\/dL (8.5\u201311.5) with normal levels of phosphorus and alkaline phosphatase. Workup for hypercalcemia revealed parathyroid hormone (PTH) of 14 pg\/mL (10\u201365), 25 hydroxy vitamin D at 19.6 ng\/mL (30\u2013100), 1,25 dihydroxy vitamin D at 6.7 pg\/mL (19.9\u201379.3), thyroid-stimulating hormone of 1.265 \u03bcIU\/mL (0.5\u20135), undetectable PTH-related protein (PTHrP) and lactate dehydrogenase of 433 U\/L (100\u2013220). The urine calcium creatinine ratio was 0.388. Reverse transcriptase PCR was positive for HTLV-1 and negative for HTLV-2. Peripheral blood flow cytometry and lymph node biopsy confirmed ATLL. He received treatment with fluids, calcitonin and denosumab after which serum calcium levels fell (nadir: 7.7 mg\/dL) and then normalized. Humoral hypercalcemia in this setting is mediated by receptor activator of nuclear factor-kappa B ligand (RANKL), PTHrP and other cytokines. PTHrP levels depend on levels of the TAX gene product, cell type and lymphocyte-specific factors. Thus, a low level, like in our patient, does not rule out HTLV-1 infection\/ATLL as the cause of hypercalcemia. Hypercalcemia is known to be responsive to monoclonal antibodies against RANKL given the compound\u2019s role in mediating hypercalcemia in these cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Human T-cell lymphotropic virus-1 infection and adult T-cell leukemia and lymphoma are associated with high rates of hypercalcemia and hypercalcemic crises.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Hypercalcemia in these cases is mediated by osteoclastic bone resorption carried out by several agents including receptor activator of nuclear factor-kappa B ligand, parathyroid hormone-related protein (PTHrP), macrophage inflammatory protein 1 alpha, interleukins, etc. A normal PTHRrP does not rule out humoral hypercalcemia of malignancy in this setting, as indicated by this case.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Hypercalcemia in such settings is highly responsive to monoclonal antibodies against RANKL given the role the ligand plays in resorptive hypercalcemia.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-22-0299","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T12:55:46Z","timestamp":1663851346000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":3,"title":["Hypercalcemia in the setting of HTLV-1 infection and a normal PTHrP level"],"prefix":"10.1530","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-8585","authenticated-orcid":true,"given":"Keerthana","family":"Haridas","sequence":"first","affiliation":[{"name":"PGY2, Internal Medicine, Icahn School of Medicine, Mount Sinai St Luke\u2019s\/West, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Journal of the Royal Society of Medicine","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1177\/014107680309600306","article-title":"Severe refractory hypercalcaemia in HTLV-1 infection","volume":"96","author":"Edwards","year":"2003","unstructured":"Edwards CMEdwards SJBhumbra RPChowdhury TA. 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