{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:36:40Z","timestamp":1790613400587,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministero della Salute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diagnosis of primary hyperparathyroidism (PHPT) relies on the detection of hypercalcemia and increased circulating parathormone (PTH) levels. However, the disease induces a deep deregulation of phosphate metabolism. A total of 960 PHPT patients (848 females, 112 males) were retrospectively enrolled; biochemical and clinical data were collected at PHPT diagnosis. At variance with previous studies, hypophosphatemia was diagnosed using sex- and age-specific serum phosphate reference range. Reduced serum phosphate levels were detectable in 49% of PHPT males and 55% of PHPT females. Moderate hypophosphatemia (\u22642.0 mg\/dL) was more frequent in men than in women, and serum phosphate levels were lower in postmenopausal than premenopausal PHPT women. Vitamin D status did not alter the prevalence of hypophosphatemia. Serum phosphate levels negatively correlated with ionized calcium and PTH levels across PHPT premenopausal women, postmenopausal women, and men. Cluster analysis integrating the three interrelated parameters identified three distinct PHPT phenotypes: bone and kidney complications were more frequent in patients with more severe hypercalcemia and hypophosphatemia, though fractures were more abundant in the less severe phenotypes. Finally, considering the whole cohort, ionized calcium and PTH levels displayed a negative non-linear correlation with phosphate levels. In conclusion, hypophosphatemia in PHPT patients is common, and moderate hypophosphatemia is more frequent in males compared to females. Menopausal status is associated with less severe hypophosphatemia and PHPT disease. Hypophosphatemia is mainly determined by parathyroid tumor cells\u2019 dysfunction. The non-linear negative relationships between phosphate, PTH and ionized calcium may suggest heterogeneous insensitivity of tumor parathyroid cells to extracellular phosphate.<\/jats:p>","DOI":"10.3390\/ijms27042012","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T10:32:37Z","timestamp":1771583557000},"page":"2012","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Gender, Menopause, Vitamin D Status, and Tumor Parathyroid Cell Activity on Serum Phosphate Levels in a Large Cohort of Patients with Sporadic Hypercalcemic Primary Hyperparathyroidism"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4318-7218","authenticated-orcid":false,"given":"Matteo","family":"Corbetta","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4477-4935","authenticated-orcid":false,"given":"Silvia","family":"Carrara","sequence":"additional","affiliation":[{"name":"Bone Metabolism Diseases and Diabetes Unit, IRCCS Istituto Auxologico Italiano, 20145 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dal Lago","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Mirsepanj","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5766-2657","authenticated-orcid":false,"given":"Elena","family":"Ruotolo","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sardella","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo De","family":"Leo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-9547","authenticated-orcid":false,"given":"Filomena","family":"Cetani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"},{"name":"Unit of Endocrinology, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8140-3175","authenticated-orcid":false,"given":"Sabrina","family":"Corbetta","sequence":"additional","affiliation":[{"name":"Bone Metabolism Diseases and Diabetes Unit, IRCCS Istituto Auxologico Italiano, 20145 Milan, Italy"},{"name":"Department of Biochemical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s11154-024-09899-5","article-title":"Primary hyperparathyroidism: From guidelines to outpatient clinic","volume":"25","author":"Palermo","year":"2024","journal-title":"Rev. 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