{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:51:33Z","timestamp":1791417093439,"version":"4.3.3"},"reference-count":22,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aims of this study were to compare the biochemical characteristics of primary\n                    hyperparathyroidism and normocalcemic primary hyperparathyroidism and\n                    to evaluate the diagnostic performance of routinely available biochemical\n                    markers using validated patient-level multivariable statistical modeling. This\n                    retrospective multicenter study screened 1,832 individuals between January 2018\n                    and December 2023. Baseline descriptive characteristics were obtained from an\n                    initial retrospective clinical cohort comprising 1,575 patients. Following the\n                    verification of the original database, duplicate encounters were consolidated,\n                    and all inferential statistical analyses were reconstructed at the patient level\n                    using the first eligible encounter for each patient. The final analytical cohort\n                    consisted of 375 patients (177 primary hyperparathyroidism and 198 normocalcemic\n                    primary hyperparathyroidism). Multivariable logistic regression with\n                    patient-level stratified cross-validation, bootstrap resampling and permutation\n                    testing, along with Spearman's correlation analyses, was performed. The\n                    effect of the synthetic minority over-sampling technique was evaluated using\n                    in-fold resampling. In the verified patient-level cohort, the multivariable\n                    logistic regression model demonstrated modest discrimination between primary\n                    hyperparathyroidism and normocalcemic primary hyperparathyroidism area under the\n                    curve: 0.578; 95% confidence interval: 0.516\u20130.639). Permutation testing\n                    indicated a statistically significant but limited diagnostic signal\n                    (p=0.02). Application of the synthetic minority over-sampling technique\n                    did not materially improve model performance (area under the curve: 0.577). No\n                    significant association was observed between the parathyroid hormone and\n                    25-hydroxyvitamin D in the overall cohort (Spearman's \u03c1=\u2212\u20090.079,\n                        p=0.185) or within the primary hyperparathyroidism and normocalcemic\n                    primary hyperparathyroidism subgroups. An exploratory visit-level screening\n                    model based solely on laboratory test-ordering patterns achieved higher\n                    discrimination (area under the curve: 0.733), suggesting that laboratory\n                    test-ordering patterns contributed to the observed classification signal.\n                    Primary hyperparathyroidism and normocalcemic primary hyperparathyroidism\n                    exhibit overlapping biochemical characteristics that provide only modest\n                    patient-level discrimination when evaluated using routinely available laboratory\n                    variables. Multivariable predictive modeling demonstrated limited diagnostic\n                    performance after rigorous patient-level validation, and the synthetic minority\n                    over-sampling technique did not improve model performance. These findings\n                    underscore the importance of patient-level validation and standardized\n                    analytical pipelines when developing predictive models using retrospective\n                    clinical data sets. Prospective studies with standardized biochemical assessment\n                    and external validation are required before such predictive models can be\n                    considered for routine clinical applications.<\/jats:p>","DOI":"10.1055\/a-2961-7052","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:22:15Z","timestamp":1791415335000},"source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Performance of Routine Biochemical Markers and Internally\n                    Validated Multivariable Models in Primary and Normocalcemic Primary\n                    Hyperparathyroidism: A Multicenter Retrospective Study"],"prefix":"10.1055","author":[{"given":"Ber\u00e7em","family":"Ay\u00e7i\u00e7ek","sequence":"additional","affiliation":[{"name":"Istinye Universitesi, Istanbul, Turkey","place":["Istanbul"],"department":["Endocrinology and Metabolism Disease"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musab Ahmed","family":"Khan Umair","sequence":"additional","affiliation":[{"name":"Istinye Universitesi, Istanbul, Turkey","place":["SARIYER"],"department":["Department of Artificial Intelligence"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eenol","family":"Pi\u015fkin","sequence":"additional","affiliation":[{"name":"Istinye Universitesi, Istanbul, Turkey","place":["Istanbul"],"department":["Department of Mechanical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.S. Femilda","family":"Josephin","sequence":"additional","affiliation":[{"name":"Istinye Universitesi, Istanbul, Turkey","place":["Istanbul"],"department":["Department of Computer Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umit","family":"\u00c7avdar","sequence":"additional","affiliation":[{"name":"Izmir Katip Celebi University, Izmir, Turkey","place":["\u00c7i\u011fli"],"department":["Endocrinology and Metabolism Disease"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beyza Zeynep","family":"Kocabi\u00e7ak","sequence":"additional","affiliation":[{"name":"Tokat Gaziosmanpasa Universitesi, Tokat, Turkey","place":["Tokat"],"department":["Department of Cardiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"Eren","sequence":"additional","affiliation":[{"name":"Izmir Katip Celebi University, Izmir, Turkey","place":["\u00c7i\u011fli"],"department":["Endocrinology and Metabolism Disease"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadir Alper","family":"K\u00fc\u00e7\u00fcker","sequence":"additional","affiliation":[{"name":"Izmir Katip \u00c7elebi \u00dcniversitesi, Islami Ilimler\n                    Fak\u00fcltesi, Izmir, Turkey","place":["Izmir"],"department":["Nuclear Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tevhid","family":"Turan","sequence":"additional","affiliation":[{"name":"MLPCARE, Istanbul, Turkey","place":["Istanbul"],"department":["Information Technology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazhar Muslum","family":"Tuna","sequence":"additional","affiliation":[{"name":"Umraniye EAH, Istanbul, Turkey","place":["Il\u00e7e Se\u00e7iniz"],"department":["Endocrinology and Metabolism"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersen","family":"Karakili\u00e7","sequence":"additional","affiliation":[{"name":"Canakkale Onsekiz Mart Universitesi, \u00c7anakkale, Turkey","place":["\u00c7anakkale"],"department":["Endocrinology and Metabolism Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumeysa","family":"Sahinba\u015f","sequence":"additional","affiliation":[{"name":"MLPCARE, Istanbul, Turkey","place":["Istanbul"],"department":["Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remziye","family":"\u00c7etin","sequence":"additional","affiliation":[{"name":"MLPCARE, Istanbul, Turkey","place":["Istanbul"],"department":["Medicine Faculty"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denizcan","family":"Demir","sequence":"additional","affiliation":[{"name":"MLPCARE, Istanbul, Turkey","place":["Istanbul"],"department":["Medicine Faculty"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcmran","family":"Keskin","sequence":"additional","affiliation":[{"name":"Umraniye EAH, Istanbul, Turkey","place":["Istanbul"],"department":["Endocrinology and Metabolism Disease"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melda","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Umraniye EAH, Istanbul, Turkey","place":["Istanbul"],"department":["Endocrinology and Metabolism Disease"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7a\u011fri","family":"Canbolat","sequence":"additional","affiliation":[{"name":"MLPCARE, Istanbul, Turkey","place":["Istanbul"],"department":["Department of Neurosurgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"Nizamo\u011flu","sequence":"additional","affiliation":[{"name":"MLPCARE, Istanbul, Turkey","place":["Istanbul"],"department":["Family Medicine Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beyza Nur","family":"Yazici","sequence":"additional","affiliation":[{"name":"Istinye Universitesi, Istanbul, Turkey","place":["Istanbul"],"department":["Department of Mechanical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceren","family":"Tufan","sequence":"additional","affiliation":[{"name":"\u00c7anakkale Onsekiz Mart University, \u00c7anakkale, Turkey","place":["\u00c7anakkale"],"department":["Endocrinology and Metabolism"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sedat","family":"\u00c7etin","sequence":"additional","affiliation":[{"name":"Diyarbakir SBU Gazi Yasargil Egitim Ve Arastirma\n                    Hastanesi, Diyarbak\u0131r, Turkey","place":["Diyarbak\u0131r"],"department":["Endocrinology and Metabolism Disease"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seval","family":"Erhamamci","sequence":"additional","affiliation":[{"name":"Umraniye EAH, Istanbul, Turkey","place":["Istanbul"],"department":["Department of Nuclear 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     hyperparathyroidism","volume":"68","author":"N Bestepe","year":"2022","journal-title":"Rev Assoc Med Bras (1992)"},{"issue":"03","key":"ref19","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.eprac.2023.12.004","article-title":"The Ca*Cl\/P ratio: a novel and more appropriate screening tool for\n                    normocalcaemic or overt primary hyperparathyroidism","volume":"30","author":"Y Yu","year":"2024","journal-title":"Endocr Pract"},{"issue":"07","key":"ref20","doi-asserted-by":"publisher","first-page":"e2689","DOI":"10.1210\/clinem\/dgaa165","article-title":"Normocalcemic hyperparathyroidism: study of its prevalence and natural\n                    history","volume":"105","author":"M Schini","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"01","key":"ref21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12020-021-02919-4","article-title":"Normocalcemic primary hyperparathyroidism","volume":"75","author":"N E Cusano","year":"2022","journal-title":"Endocrine."},{"issue":"02","key":"ref22","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/cphy.c140071","article-title":"PTH and vitamin D","volume":"6","author":"S J Khundmiri","year":"2016","journal-title":"Compr Physiol"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2961-7052.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:22:17Z","timestamp":1791415337000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2961-7052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":22,"URL":"https:\/\/doi.org\/10.1055\/a-2961-7052","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}