{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:01:01Z","timestamp":1790744461092,"version":"4.1.0"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Primary hyperparathyroidism (PHPT) is a clinically heterogeneous endocrine disorder whose management has historically been guided by biochemical profiles and symptomatic presentation. However, the limitations of conventional diagnostic and therapeutic strategies\u2014including poor sensitivity in detecting subclinical organ damage and an inability to predict disease progression\u2014have underscored the need for a more nuanced, biomarker-driven approach. Recent advances in multi-omics technologies, functional imaging, and artificial intelligence have enabled the emergence of precision medicine paradigms for PHPT. This review synthesizes evidence on the role of multilevel biomarkers\u2014spanning genetic, epigenetic, non-coding RNA, metabolic, and imaging domains\u2014in refining risk stratification and guiding individualized treatment. We further propose an integrated framework that combines dynamic biomarker profiling with multidisciplinary team (MDT)-based decision-making to facilitate personalized intervention pathways\u2014from surgical planning to long-term surveillance. Despite promising developments, clinical translation remains challenged by the lack of standardized biomarker validation and integrative analytical platforms. Future efforts should prioritize collaborative networks and large-scale prospective studies to establish evidence-based guidelines for implementing precision medicine in PHPT.<\/jats:p>","DOI":"10.3389\/fendo.2025.1688399","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T04:14:09Z","timestamp":1761279249000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Precision stratified treatment of primary hyperparathyroidism based on multilevel emerging biomarkers"],"prefix":"10.3389","volume":"16","author":[{"given":"Xi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enmei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101700","DOI":"10.1016\/j.ando.2025.101700","article-title":"Chapter 11: treatment modalities","volume":"86","author":"Baud","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2015-203186","article-title":"Clinicopathological correlates of hyperparathyroidism","volume":"68","author":"Duan","year":"2015","journal-title":"J Clin Pathol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2016.33","article-title":"Primary hyperparathyroidism","volume":"2","author":"Bilezikian","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23337","article-title":"Molecular genetics of syndromic and non-syndromic forms of parathyroid carcinoma","volume":"38","author":"Cardoso","year":"2017","journal-title":"Hum Mutat"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31430-7","article-title":"Hyperparathyroidism","volume":"391","author":"Bilezikian","year":"2018","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.5603\/ep.95820","article-title":"Secondary hyperparathyroidism in chronic kidney disease: pathomechanism and current treatment possibilities","volume":"74","author":"Rodzon\u0301-Norwicz","year":"2023","journal-title":"Endokrynologia Polska"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1159\/000441095","article-title":"Treatment failure of active vitamin D therapy in chronic kidney disease: predictive factors","volume":"42","author":"Cozzolino","year":"2015","journal-title":"Am J Nephrol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1059828","article-title":"Advances in the treatment of secondary and tertiary hyperparathyroidism","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvad013","article-title":"The eucalcemic patient with elevated parathyroid hormone levels","volume":"7","author":"Shaker","year":"2023","journal-title":"J Endocrine Soc"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.8753","article-title":"Tertiary hyperparathyroidism masking an atypical parathyroid tumor","volume":"12","author":"Laskou","year":"2024","journal-title":"Clin Case Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1221060","article-title":"Specific genetic aberrations of parathyroid in chinese patients with tertiary hyperparathyroidism using whole-exome sequencing","volume":"14","author":"Li","year":"2023","journal-title":"Front Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"101690","DOI":"10.1016\/j.ando.2025.101690","article-title":"Chapter 1: Epidemiology of primary hyperparathyroidism","volume":"86","author":"Cuny","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4665","article-title":"Epidemiology, pathophysiology, and genetics of primary hyperparathyroidism","volume":"37","author":"Minisola","year":"2020","journal-title":"J Bone Mineral Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.21569.1","article-title":"Recent advances in the understanding and management of primary hyperparathyroidism","volume":"9","author":"Goldfarb","year":"2020","journal-title":"F1000Research"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3993","DOI":"10.1210\/jc.2018-01225","article-title":"Primary hyperparathyroidism","volume":"103","author":"Bilezikian","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B16","doi-asserted-by":"publisher","first-page":"20406223211015965","DOI":"10.1177\/20406223211015965","article-title":"Advances in the diagnosis and the management of primary hyperparathyroidism","volume":"12","author":"Islam","year":"2021","journal-title":"Ther Adv Chronic Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.19078","article-title":"A clinical review of the psychiatric sequelae of primary hyperparathyroidism","volume":"13","author":"Serdenes","year":"2021","journal-title":"Cureus"},{"key":"B18","doi-asserted-by":"publisher","first-page":"6349","DOI":"10.3390\/ijms25126349","article-title":"Turning points in cross-disciplinary perspective of primary hyperparathyroidism and pancreas involvements: hypercalcemia-induced pancreatitis, MEN1 gene-related tumors, and insulin resistance","volume":"25","author":"Carsote","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.16966\/2380-548X.150","article-title":"Primary hyperparathyroidism: an update and in-depth review of the literature","volume":"4","author":"Yorke","year":"2018","journal-title":"Int J Endocrinol Metab Disord"},{"key":"B20","doi-asserted-by":"publisher","first-page":"101691","DOI":"10.1016\/j.ando.2025.101691","article-title":"Chapter 2: primary hyperparathyroidism: diagnosis","volume":"86","author":"Bouillet","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B21","doi-asserted-by":"publisher","first-page":"101692","DOI":"10.1016\/j.ando.2025.101692","article-title":"Chapter 3: Impact of primary hyperparathyroidism","volume":"86","author":"Scheyer","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B22","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3390\/jcm9020308","article-title":"Primary hyperparathyroidism in sickle cell disease: an unknown complication of the disease in adulthood","volume":"9","author":"Denoix","year":"2020","journal-title":"J Clin Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2018.5365","article-title":"Update of the tolerable upper intake level for vitamin D for infants","volume":"16","author":"Turck","year":"2018","journal-title":"EFSA J"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.44115","article-title":"The impact of moderate hypophosphatemia on the clinical management of primary hyperparathyroidism","volume":"15","author":"G\u00fcne\u015f","year":"2023","journal-title":"Cureus"},{"key":"B25","doi-asserted-by":"publisher","first-page":"101698","DOI":"10.1016\/j.ando.2025.101698","article-title":"Chapter 9: Indications for the treatment of primary hyperparathyroidism","volume":"86","author":"Frey","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000557","article-title":"Surgery for primary hyperparathyroidism","volume":"66","author":"Neves","year":"2022","journal-title":"Arch Endocrinol Metab"},{"key":"B27","doi-asserted-by":"publisher","first-page":"101701","DOI":"10.1016\/j.ando.2025.101701","article-title":"Chapter 12: Preparation for parathyroid surgery","volume":"86","author":"Lecoq","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000117","article-title":"Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism","volume":"63","author":"Rosario","year":"2019","journal-title":"Arch Endocrinol Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4665","article-title":"Epidemiology, pathophysiology, and genetics of primary hyperparathyroidism","volume":"37","author":"Minisola","year":"2022","journal-title":"J Bone Mineral Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"36","DOI":"10.21037\/apm-22-1171","article-title":"Changes in the pathophysiology of primary hyperparathyroidism and analysis of postoperative recurrence cases at a regional core hospital in Japan: experience of 35 years in Shinshu University Hospital","volume":"12","author":"Kanai","year":"2022","journal-title":"Ann Palliative Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-020-01142-w","article-title":"Progressive rise in the prevalence of asymptomatic primary hyperparathyroidism in India: Data from PHPT registry","volume":"39","author":"Arya","year":"2021","journal-title":"J Bone Mineral Metab"},{"key":"B32","doi-asserted-by":"publisher","first-page":"101980","DOI":"10.1016\/j.beem.2025.101980","article-title":"Changing trends in clinical presentation of primary hyperparathyroidism across countries over time","volume":"39","author":"Arjunan","year":"2025","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad267","article-title":"Incidence of primary hyperparathyroidism in the current era: have we finally reached a steady state","volume":"108","author":"Wermers","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B34","doi-asserted-by":"publisher","first-page":"100317","DOI":"10.1016\/j.jcte.2023.100317","article-title":"Symptomatic versus asymptomatic primary hyperparathyroidism: A systematic review and meta-analysis","volume":"32","author":"Kulkarni","year":"2023","journal-title":"J Clin Trans Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"101703","DOI":"10.1016\/j.ando.2025.101703","article-title":"Chapter 14: Post surgical follow-up of primary hyperparathyroidism","volume":"86","author":"Barraud","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B36","doi-asserted-by":"publisher","first-page":"101704","DOI":"10.1016\/j.ando.2025.101704","article-title":"Chapter 15: Recurrent or persistent primary hyperparathyroidism, parathyromatosis","volume":"86","author":"Ladsous","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab240","article-title":"Effectiveness and safety of thermal ablation in the treatment of primary hyperparathyroidism: a multicenter study","volume":"106","author":"Wei","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B38","doi-asserted-by":"publisher","first-page":"555","DOI":"10.3348\/kjr.2021.0716","article-title":"Efficacy and safety of ultrasound-guided radiofrequency ablation for primary hyperparathyroidism: A prospective study","volume":"23","author":"Chai","year":"2022","journal-title":"Korean J Radiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1530\/EC-20-0221","article-title":"Cinacalcet and primary hyperparathyroidism: systematic review and meta regression","volume":"9","author":"Ng","year":"2020","journal-title":"Endocrine connections"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4236\/ijcm.2014.514111","article-title":"Long term outcome of bisphosphonate therapy in patients with primary hyperparathyroidism","volume":"2014","author":"Segula","year":"2014","journal-title":"Int J Clin Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"101699","DOI":"10.1016\/j.ando.2025.101699","article-title":"Chapter 10: What parathyroid imaging is required for hyperparathyroidism","volume":"86","author":"Chevalier","year":"2025","journal-title":"Annales d'Endocrinologie"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1165890","article-title":"Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism","volume":"14","author":"Lu","year":"2023","journal-title":"Front Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-024-11159-8","article-title":"Machine learning-derived clinical decision algorithm for the diagnosis of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism","volume":"35","author":"Yeh","year":"2025","journal-title":"Eur Radiol"},{"key":"B44","article-title":"High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria","volume":"28","author":"Glendenning","year":"1998","journal-title":"Aust New Z J Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1590\/1806-9282.20220645","article-title":"Serum calcium\/phosphorus ratio in biochemical screening of primary hyperparathyroidism","volume":"68","author":"Bestepe","year":"2022","journal-title":"Rev da Associa\u00e7\u00e3o M\u00e9dica Bras"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-023-02260-8","article-title":"Calcium\/phosphate ratio: an additional tool for the clinical management of asymptomatic primary hyperparathyroidism","volume":"47","author":"Castellano","year":"2024","journal-title":"J Endocrinological Invest"},{"key":"B47","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.metabol.2017.06.004","article-title":"Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density","volume":"74","author":"Weber","year":"2017","journal-title":"Metabolism"},{"key":"B48","doi-asserted-by":"publisher","first-page":"115583","DOI":"10.1016\/j.bone.2020.115583","article-title":"Impaired physical function and evaluation of quality of life in normocalcemic and hypercalcemic primary hyperparathyroidism","volume":"141","author":"Voss","year":"2020","journal-title":"Bone"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab676","article-title":"Serum phosphate: a neglected test in the clinical management of primary hyperparathyroidism","volume":"107","author":"Castellano","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-023-02284-0","article-title":"Ultrasound-based quantitative tools in predicting renal involvement in asymptomatic primary hyperparathyroidism","volume":"47","author":"Candemir","year":"2024","journal-title":"J Endocrinological Invest"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1055\/a-0664-7820","article-title":"The abdominal aortic intima-media thickness increases in patients with primary hyperparathyroidism","volume":"127","author":"Sumbul","year":"2019","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03558.x","article-title":"Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women","volume":"71","author":"Ahlstr\u00f6m","year":"2009","journal-title":"Clin Endocrinol"},{"key":"B53","doi-asserted-by":"crossref","DOI":"10.1016\/j.ando.2022.10.015","article-title":"Spectrum of renal dysfunction after curative parathyroidectomy in symptomatic primary hyperparathyroidism","author":"Gosavi","year":"2023"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000511","article-title":"Primary hyperparathyroidism: recent advances","volume":"30","author":"Walker","year":"2018","journal-title":"Curr Opin Rheumatol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4679","article-title":"Classical and nonclassical manifestations of primary hyperparathyroidism","volume":"37","author":"Fuleihan","year":"2020","journal-title":"J Bone Mineral Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181f66720","article-title":"The effects of serum calcium and parathyroid hormone changes on psychological and cognitive function in patients undergoing parathyroidectomy for primary hyperparathyroidism","volume":"253","author":"Roman","year":"2011","journal-title":"Ann Surg"},{"key":"B57","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.bone.2016.05.012","article-title":"Seasonal changes in serum calcium, PTH and vitamin D levels in patients with primary hyperparathyroidism","volume":"89","author":"Nevo-Shor","year":"2016","journal-title":"Bone"},{"key":"B58","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41574-021-00470-9","article-title":"The importance of the RET gene in thyroid cancer and therapeutic implications","volume":"17","author":"Salvatore","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-022-01948-7","article-title":"Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism","volume":"46","author":"Mazarico-Altisent","year":"2023","journal-title":"J endocrinological Invest"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.4158\/EP-2020-0132","article-title":"Germline GCM2 mutation screening in Chinese primary hyperparathyroidism patients","volume":"26","author":"Song","year":"2020","journal-title":"Endocrine Pract"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz233","article-title":"Neonatal severe hyperparathyroidism: novel insights from calcium, PTH, and the CASR gene","volume":"105","author":"Marx","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.46980","article-title":"Coexistence of a calcium-sensing receptor mutation and primary hyperparathyroidism","volume":"15","author":"Russell","year":"2023","journal-title":"Cureus"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02517","article-title":"Analysis of activating GCM2 sequence variants in sporadic parathyroid adenomas","volume":"104","author":"Riccardi","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13304-025-02179-0","article-title":"Germline mutations of GCM2 cause a novel variant of hereditary primary hyperparathyroidism","volume":"2025","author":"Iacobone","year":"2025","journal-title":"Updates Surg"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab929","article-title":"GCM2 variants in familial and multiglandular primary hyperparathyroidism","volume":"107","author":"Vincze","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.05.010","article-title":"Alterations of DNA methylation in parathyroid tumors","volume":"469","author":"Guarnieri","year":"2018","journal-title":"Mol Cell Endocrinol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12458","article-title":"Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours","volume":"280","author":"Westin","year":"2016","journal-title":"J Internal Med"},{"key":"B68","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1210\/endrev\/bnad009","article-title":"Molecular and clinical spectrum of primary hyperparathyroidism","volume":"44","author":"Jha","year":"2023","journal-title":"Endocrine Rev"},{"key":"B69","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1186\/s12967-022-03568-4","article-title":"Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm","volume":"20","author":"Zhou","year":"2022","journal-title":"J Trans Med"},{"key":"B70","doi-asserted-by":"publisher","first-page":"115350","DOI":"10.1016\/j.bone.2020.115350","article-title":"Circulating fractures-related microRNAs distinguish primary hyperparathyroidism-related from estrogen withdrawal-related osteoporosis in postmenopausal osteoporotic women: a pilot study","volume":"137","author":"Verdelli","year":"2020","journal-title":"Bone"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab048.524","article-title":"Circulating microRNA-23a-5p is a potential biomarker for recovery of bone mass after parathyroidectomy in primary hyperparathyroidism","volume":"5","author":"Lee","year":"2021","journal-title":"J Endocrine Soc"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.3390\/diagnostics11091704","article-title":"Circulating miR-122-5p and miR-375 as potential biomarkers for bone mass recovery after parathyroidectomy in patients with primary hyperparathyroidism: a proof-of-concept study","volume":"11","author":"Lee","year":"2021","journal-title":"Diagnostics"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11598","article-title":"Association between hsa-mir-30e polymorphisms and sporadic primary hyperparathyroidism risk","volume":"33","author":"Mizamtsidi","year":"2019","journal-title":"Vivo"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.284","article-title":"Serum circulating miRNA-342-3p as a potential diagnostic biomarker in parathyroid carcinomas: A pilot study","volume":"4","author":"Krupinova","year":"2021","journal-title":"Endocrinology Diabetes Metab"},{"key":"B75","doi-asserted-by":"publisher","first-page":"876","DOI":"10.3390\/cancers14040876","article-title":"MicroRNA profile alterations in parathyroid carcinoma: Latest updates and perspectives","volume":"14","author":"Wielogo\u0301rska","year":"2022","journal-title":"Cancers"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1551-2","article-title":"Verification of candidate microRNA markers for parathyroid carcinoma","volume":"60","author":"Hu","year":"2018","journal-title":"Endocrine"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-020-02535-7","article-title":"Expression profile of serum-related exosomal miRNAs from parathyroid tumor","volume":"72","author":"Wang","year":"2021","journal-title":"Endocrine"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-18-0480","article-title":"Profiling analysis of long non-coding RNA and mRNA in parathyroid carcinoma","volume":"26","author":"Zhang","year":"2019","journal-title":"Endocrine-related Cancer"},{"key":"B79","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s40463-021-00509-x","article-title":"Role of LncRNA score and PVT1 in primary hyperparathyroidism\u2013a preliminary study","volume":"50","author":"Zhang","year":"2021","journal-title":"J Otolaryngology-Head Neck Surg"},{"key":"B80","doi-asserted-by":"publisher","first-page":"4392","DOI":"10.3390\/ijms25084392","article-title":"TRPC3 is downregulated in primary hyperparathyroidism","volume":"25","author":"Kirstein","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B81","doi-asserted-by":"publisher","first-page":"6435","DOI":"10.1038\/s41598-024-57100-3","article-title":"Unveiling potential drug targets for hyperparathyroidism through genetic insights via mendelian randomization and colocalization analyses","volume":"14","author":"Chen","year":"2024","journal-title":"Sci Rep"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2025.101985","article-title":"Molecular basis of symptomatic sporadic primary hyperparathyroidism: new frontiers in pathogenesis","volume":"101985","author":"Arya","year":"2025","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-021-01646-w","article-title":"CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study","volume":"45","author":"Agarwal","year":"2022","journal-title":"J Endocrinological Invest"},{"key":"B84","doi-asserted-by":"crossref","DOI":"10.32322\/jhsm.1721141","article-title":"Clinical significance of chloride-to-phosphorus and chloride-to-magnesium ratios in primary hyperparathyroidism","author":"Erdo\u011fan","year":"2025"},{"key":"B85","doi-asserted-by":"publisher","first-page":"109982","DOI":"10.1016\/j.mehy.2020.109982","article-title":"Otoconia degeneration as a consequence of primary hyperparathyroidism","volume":"144","author":"Mckenna","year":"2020","journal-title":"Med Hypotheses"},{"key":"B86","doi-asserted-by":"crossref","DOI":"10.1530\/endoabs.90.EP125","article-title":"Application of untargeted metabolomics in primary hyperparathyroidism","author":"Wielogorska-Partyka","year":"2023"},{"key":"B87","doi-asserted-by":"publisher","first-page":"20987","DOI":"10.1038\/s41598-024-71423-1","article-title":"New insight into primary hyperparathyroidism using untargeted metabolomics","volume":"14","author":"Wielogo\u0301rska-Partyka","year":"2024","journal-title":"Sci Rep"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2018.74758","article-title":"Association between neutrophil-to-lymphocyte ratio and parathyroid hormone in patients with primary hyperparathyroidism","volume":"15","author":"Lam","year":"2019","journal-title":"Arch Med Sci"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1159\/000334588","article-title":"Inflammatory biomarkers in patients with asymptomatic primary hyperparathyroidism","volume":"21","author":"Emam","year":"2012","journal-title":"Med Principles Pract"},{"key":"B90","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1530\/EJE-14-1038","article-title":"Novel inflammatory biomarkers in primary hyperparathyroidism","volume":"173","author":"Christensen","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10019","article-title":"Serum calcium to phosphorous (Ca\/P) ratio is a simple, inexpensive, and accurate tool in the diagnosis of primary hyperparathyroidism","volume":"2","author":"Madeo","year":"2018","journal-title":"J Bone Mineral Res Plus"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2023.12.004","article-title":"The Ca\u2217 Cl\/P ratio: a novel and more appropriate screening tool for normocalcaemic or overt primary hyperparathyroidism","volume":"30","author":"Yu","year":"2024","journal-title":"Endocrine Pract"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12902-019-0487-8","article-title":"New parathyroid function index for the differentiation of primary and secondary hyperparathyroidism: a case-control study","volume":"20","author":"Guo","year":"2020","journal-title":"BMC Endocrine Disord"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae659","article-title":"Approach to the patient: normocalcemic primary hyperparathyroidism","volume":"110","author":"Liu","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2024.115825","article-title":"Establishing the diagnosis of normocalcaemic primary hyperparathyroidism","volume":"236","author":"Mihai","year":"2024","journal-title":"Am J Surg"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14064","article-title":"Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers","volume":"91","author":"Cipriani","year":"2019","journal-title":"Clin Endocrinol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-22-0206","article-title":"Primary hyperparathyroidism, a machine learning approach to identify multiglandular disease in patients with a single adenoma found at preoperative sestamibi-SPECT\/CT","volume":"187","author":"Sandqvist","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s42000-023-00508-9","article-title":"Genetics of hereditary forms of primary hyperparathyroidism","volume":"23","author":"English","year":"2024","journal-title":"Hormones"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2025.101975","article-title":"Adolescent primary hyperparathyroidism","volume":"101975","author":"Sharma","year":"2025","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3296","article-title":"Hypercalcemic disorders in children","volume":"32","author":"Stokes","year":"2017","journal-title":"J Bone Mineral Res"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4677","article-title":"Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop","volume":"37","author":"Bilezikian","year":"2020","journal-title":"J Bone Mineral Res"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-021-02927-3","article-title":"A contemporary clinical approach to genetic testing for heritable hyperparathyroidism syndromes","volume":"75","author":"De Sousa","year":"2022","journal-title":"Endocrine"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.853171","article-title":"Germline mutations related to primary hyperparathyroidism identified by next-generation sequencing","volume":"13","author":"Park","year":"2022","journal-title":"Front Endocrinol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.48332","article-title":"Analysis of time to diagnosis and outcomes among adults with primary hyperparathyroidism","volume":"5","author":"Lorenz","year":"2022","journal-title":"JAMA network Open"},{"key":"B105","doi-asserted-by":"publisher","first-page":"100170","DOI":"10.1016\/j.endmts.2024.100170","article-title":"Development of a machine learning model for the diagnosis of atypical primary hyperparathyroidism","volume":"15","author":"O\u2019brien","year":"2024","journal-title":"Endocrine Metab Sci"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2016.09.044","article-title":"Improving diagnostic recognition of primary hyperparathyroidism with machine learning","volume":"161","author":"Somnay","year":"2017","journal-title":"Surgery"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26970","article-title":"Machine learning can identify patients at risk of hyperparathyroidism without known calcium and intact parathyroid hormone","volume":"44","author":"Greer","year":"2022","journal-title":"Head Neck"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.15396","article-title":"Analysis of comorbidities, clinical outcomes, and parathyroidectomy in adults with primary hyperparathyroidism","volume":"5","author":"Axelsson","year":"2022","journal-title":"JAMA network Open"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvae163.1057","article-title":"7845 machine learning methods in differential diagnosis of genetically confirmed multiple endocrine neoplasia type 1 and its phenocopies","volume":"8","author":"Trukhina","year":"2024","journal-title":"J Endocrine Soc"},{"key":"B110","doi-asserted-by":"publisher","first-page":"4","DOI":"10.14341\/probl13322","article-title":"Predicting the presence of MEN1 gene mutation based on the clinical phenotype of patients with primary hyperparathyroidism","volume":"69","author":"Mokrysheva","year":"2023","journal-title":"Problems Endocrinol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12880-021-00616-1","article-title":"Efficacy of ultrasonography and Tc-99m MIBI SPECT\/CT in preoperative localization of parathyroid adenomas causing primary hyperthyroidism","volume":"21","author":"Lu","year":"2021","journal-title":"BMC Med Imaging"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1595461","article-title":"Conventional imaging techniques plus 18 F-fluorocholine PET\/CT: A comparative study of diagnostic accuracy in localizing parathyroid adenomas in primary hyperparathyroidism","volume":"16","author":"Chiu","year":"2025","journal-title":"Front Endocrinol"},{"key":"B113","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s40644-025-00897-7","article-title":"Comparison of four-dimensional CT and Sestamibi SPECTCT in the localization management of primary hyperparathyroidism","volume":"25","author":"Yang","year":"2025","journal-title":"Cancer Imaging"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A6482","article-title":"4D\u2013Dynamic contrast-enhanced MRI for preoperative localization in patients with primary hyperparathyroidism","volume":"41","author":"Becker","year":"2020","journal-title":"Am J Neuroradiology"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.262395","article-title":"18F-fluorocholine PET\/CT is more sensitive than 11C-methionine PET\/CT for the localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism","volume":"63","author":"Mathey","year":"2022","journal-title":"J Nucl Med"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.5603\/ep.103003","article-title":"Contemporary localization diagnostics in primary hyperparathyroidism. Review of visualization techniques including ultrasonography, PTH washout, 99mTc-MIBI scintigraphy, and 18F-choline PET","volume":"76","author":"Witowska","year":"2025","journal-title":"Endokrynologia Polska"},{"key":"B117","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11547-025-02004-z","article-title":"Advanced radiomic prediction of osteoporosis in primary hyperparathyroidism: a machine learning-based analysis of CT images","author":"Adarve-Castro","year":"2025","journal-title":"La Radiologia Med"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-019-05186-1","article-title":"Impaired geometry, volumetric density, and microstructure of cortical and trabecular bone assessed by HR-pQCT in both sporadic and MEN1-related primary hyperparathyroidism","volume":"31","author":"Wang","year":"2020","journal-title":"Osteoporosis Int"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1007\/s40200-024-01487-3","article-title":"Advanced 3D-DXA insights into bone density changes in hyperparathyroidism","volume":"23","author":"Guerra","year":"2024","journal-title":"J Diabetes Metab Disord"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad460","article-title":"Trabecular bone score as a more sensitive tool to evaluate bone involvement in MEN1-related primary hyperparathyroidism","volume":"109","author":"Song","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1302\/2633-1462.63.BJO-2024-0107.R1","article-title":"Proposed practice parameters for the performance of radiofrequency echographic multispectrometry (REMS) evaluations","volume":"6","author":"Zambito","year":"2025","journal-title":"Bone Joint Open"},{"key":"B122","doi-asserted-by":"publisher","first-page":"6382","DOI":"10.3390\/jcm13216382","article-title":"Analysis of bone phenotype differences in MEN1-related and sporadic primary hyperparathyroidism using 3D-DXA","volume":"13","author":"Eremkina","year":"2024","journal-title":"J Clin Med"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1002\/ctd2.217","article-title":"Strategy on precision medicine multidisciplinary team in clinical practice","volume":"3","author":"Qian","year":"2023","journal-title":"Clin Trans Discov"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-023-03392-w","article-title":"Expert consensus on multidisciplinary approach to the diagnosis and treatment of primary hyperparathyroidism in pregnancy in China","volume":"82","author":"Zhong","year":"2023","journal-title":"Endocrine"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1017\/S002221511800018X","article-title":"Setting up a parathyroid multidisciplinary team meeting: one year's experience, outcomes and learning points","volume":"132","author":"Hancox","year":"2018","journal-title":"J Laryngology Otology"},{"key":"B126","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1186\/s12884-021-04042-7","article-title":"Multidisciplinary team efforts to improve the pregnancy outcome of pregnancy complicated with primary hyperparathyroidism: case series from a single hospital","volume":"21","author":"Jiao","year":"2021","journal-title":"BMC Pregnancy Childbirth"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1688399\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T04:14:10Z","timestamp":1761279250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1688399\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":126,"alternative-id":["10.3389\/fendo.2025.1688399"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1688399","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]},"article-number":"1688399"}}