{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:47:00Z","timestamp":1787021220280,"version":"build-2736575974"},"reference-count":45,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Progetti di Ricerca di Ateneo"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work aims to retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This monocentric study was conducted on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Fifty-eight patients with a confirmed histopathological diagnosis of APA, and age- and sex-matched controls with parathyroid adenoma (PA) were also included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty-four patients had sporadic PHPT and 4 had familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had symptomatic disease. Serum calcium and parathyroid hormone (PTH) levels were significantly higher in symptomatic compared to asymptomatic patients (P\u2005=\u2005.048 and .008, respectively). FIHP patients were younger than their sporadic counterparts (30\u2005\u00b1\u200517 years vs 55\u2005\u00b1\u200513 years). APA patients had significantly higher serum calcium and PTH levels and lower 25-hydroxyvitamin D concentration, bone mineral density, and T score at one-third distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was 60\u2005\u00b1\u200556.4 months. All but 6 patients (90%), 5 with apparently sporadic PHPT and 1 with FIHP, were cured after surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The large majority of patients with APA, despite a moderate\/severe phenotype, have a good prognosis. Germline CDC73 mutation\u2013positive patients had a higher rate of persistent\/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab452","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:23:21Z","timestamp":1624368201000},"page":"e4565-e4579","source":"Crossref","is-referenced-by-count":23,"title":["Do Patients With Atypical Parathyroid Adenoma Need Close Follow-up?"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0277-1648","authenticated-orcid":false,"given":"Federica","family":"Saponaro","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"},{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pardi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mazoni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Borsari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liborio","family":"Torregrossa","sequence":"additional","affiliation":[{"name":"Division of Surgical Pathology, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Apicella","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Frustaci","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Materazzi","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Miccoli","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1657-5020","authenticated-orcid":false,"given":"Fulvio","family":"Basolo","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6568-8588","authenticated-orcid":false,"given":"Claudio","family":"Marcocci","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":"Endocrine Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"issue":"11","key":"2021120108542821200_CIT0001","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s40618-018-0879-z","article-title":"Clinical presentation and management of patients with primary hyperparathyroidism in Italy","volume":"41","author":"Saponaro","year":"2018","journal-title":"J Endocrinol Invest."},{"key":"2021120108542821200_CIT0002","first-page":"145","article-title":"Tumors of the parathyroid glands","volume-title":"WHO Classification of Tumors of Endocrine Organs.","author":"DeLellis","year":"2017","edition":"4th ed."},{"issue":"7","key":"2021120108542821200_CIT0003","doi-asserted-by":"crossref","first-page":"R441","DOI":"10.1530\/ERC-19-0135","article-title":"Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors","volume":"26","author":"Cetani","year":"2019","journal-title":"Endocr Relat Cancer."},{"issue":"2","key":"2021120108542821200_CIT0004","doi-asserted-by":"crossref","first-page":"R53","DOI":"10.1530\/ERC-18-0304","article-title":"Molecular genetic insights into sporadic primary hyperparathyroidism","volume":"26","author":"Brewer","year":"2019","journal-title":"Endocr Relat Cancer."},{"issue":"10","key":"2021120108542821200_CIT0005","doi-asserted-by":"crossref","first-page":"E1995","DOI":"10.1210\/jc.2012-2303","article-title":"Whole-exome sequencing studies of nonhereditary (sporadic) parathyroid adenomas","volume":"97","author":"Newey","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021120108542821200_CIT0006","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jbmr.3650","article-title":"Evolution of our understanding of the hyperparathyroid syndromes: a historical perspective","volume":"34","author":"Marx","year":"2019","journal-title":"J Bone Miner Res."},{"issue":"18","key":"2021120108542821200_CIT0007","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1056\/NEJMoa031237","article-title":"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma","volume":"349","author":"Shattuck","year":"2003","journal-title":"N Engl J Med."},{"issue":"9","key":"2021120108542821200_CIT0008","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1136\/jmg.40.9.657","article-title":"HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours","volume":"40","author":"Howell","year":"2003","journal-title":"J Med Genet."},{"issue":"4","key":"2021120108542821200_CIT0009","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1530\/EC-13-0046","article-title":"CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer","volume":"2","author":"Cetani","year":"2013","journal-title":"Endocr Connect."},{"issue":"6","key":"2021120108542821200_CIT0010","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s13402-012-0100-x","article-title":"CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort","volume":"35","author":"Guarnieri","year":"2012","journal-title":"Cell Oncol (Dordr)."},{"issue":"6","key":"2021120108542821200_CIT0011","doi-asserted-by":"crossref","first-page":"e92061","DOI":"10.1172\/jci.insight.92061","article-title":"Genomic profiling reveals mutational landscape in parathyroid carcinomas","volume":"2","author":"Pandya","year":"2017","journal-title":"JCI Insight"},{"issue":"12","key":"2021120108542821200_CIT0012","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1210\/jc.2017-01249","article-title":"CDC73-related disorders: clinical manifestations and case detection in primary hyperparathyroidism","volume":"102","author":"van der Tuin","year":"2017","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2021120108542821200_CIT0013","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1002\/ijc.33166","article-title":"The genomic profile of parathyroid carcinoma based on whole-genome sequencing","volume":"147","author":"Hu","year":"2020","journal-title":"Int J Cancer."},{"issue":"9","key":"2021120108542821200_CIT0014","doi-asserted-by":"crossref","first-page":"e45567","DOI":"10.1371\/journal.pone.0045567","article-title":"Novel HRPT2\/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One."},{"issue":"11","key":"2021120108542821200_CIT0015","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1210\/jc.2004-0294","article-title":"Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors","volume":"89","author":"Cetani","year":"2004","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021120108542821200_CIT0016","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1365-2265.2006.02460.x","article-title":"Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours","volume":"64","author":"Bradley","year":"2006","journal-title":"Clin Endocrinol (Oxf)."},{"key":"2021120108542821200_CIT0017","doi-asserted-by":"crossref","first-page":"513","DOI":"10.55418\/9781933477329-25","article-title":"Parathyroid adenoma and variants","volume-title":"Tumors of the Thyroid and Parathyroid Glands. Armed Forces Institute of Pathology; Atlas of Tumor Pathology Series 4.","author":"Rosai","year":"2014"},{"key":"2021120108542821200_CIT0018"},{"issue":"4","key":"2021120108542821200_CIT0019","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/ng1048","article-title":"HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome","volume":"32","author":"Carpten","year":"2002","journal-title":"Nat Genet."},{"issue":"10","key":"2021120108542821200_CIT0020","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1210\/jc.2014-1413","article-title":"Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop","volume":"99","author":"Bilezikian","year":"2014","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021120108542821200_CIT0021","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1046\/j.1365-2265.2002.01502.x","article-title":"Genetic analysis of the MEN1 gene and HPRT2 locus in two Italian kindreds with familial isolated hyperparathyroidism","volume":"56","author":"Cetani","year":"2002","journal-title":"Clin Endocrinol (Oxf)."},{"key":"2021120108542821200_CIT0022","article-title":"A close look at our cases with parathyroidectomy: 11 years of experience","author":"Saraydaroglu","journal-title":"Minerva Endocrinol."},{"issue":"6","key":"2021120108542821200_CIT0023","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1590\/2359-3997000000224","article-title":"Evaluation of preoperative ultrasonographic and biochemical features of patients with aggressive parathyroid disease: is there a reliable predictive marker?","volume":"60","author":"Cakir","year":"2016","journal-title":"Arch Endocrinol Metab."},{"issue":"2","key":"2021120108542821200_CIT0024","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s12022-016-9426-7","article-title":"Role of histological criteria and immunohistochemical markers in predicting risk of malignancy in parathyroid neoplasms","volume":"27","author":"Kumari","year":"2016","journal-title":"Endocr Pathol."},{"key":"2021120108542821200_CIT0025","doi-asserted-by":"crossref","first-page":"3745239","DOI":"10.1155\/2018\/3745239","article-title":"The clinical features of cystic parathyroid adenoma in Chinese population: a single-center experience","volume":"2018","author":"Hu","year":"2018","journal-title":"Int J Endocrinol."},{"issue":"10","key":"2021120108542821200_CIT0026","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1007\/s00268-015-3149-7","article-title":"Immunohistochemical expression of E-cadherin in atypical parathyroid adenoma","volume":"39","author":"Schneider","year":"2015","journal-title":"World J Surg."},{"key":"2021120108542821200_CIT0027","doi-asserted-by":"crossref","DOI":"10.1007\/s12105-020-01281-6","article-title":"Distinguishing parathyromatosis, atypical parathyroid adenomas, and parathyroid carcinomas utilizing histologic and clinical features","author":"Schulte","year":"2021","journal-title":"Head Neck Pathol."},{"issue":"1","key":"2021120108542821200_CIT0028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12957-021-02123-7","article-title":"Atypical parathyroid adenoma: clinical and anatomical pathologic features","volume":"19","author":"Galani","year":"2021","journal-title":"World J Surg Oncol."},{"issue":"6","key":"2021120108542821200_CIT0029","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.jamcollsurg.2014.10.007","article-title":"Modern experience with aggressive parathyroid tumors in a high-volume New England referral center","volume":"220","author":"Quinn","year":"2015","journal-title":"J Am Coll Surg."},{"key":"2021120108542821200_CIT0030","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ijsu.2016.05.035","article-title":"Parathyroid carcinoma and atypical parathyroid neoplasms in MEN1 patients; a clinico-pathologic challenge. The MD Anderson case series and review of the literature","volume":"31","author":"Christakis","year":"2016","journal-title":"Int J Surg."},{"issue":"7","key":"2021120108542821200_CIT0031","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1080\/0284186X.2017.1306103","article-title":"A nationwide study on parathyroid carcinoma","volume":"56","author":"Ryh\u00e4nen","year":"2017","journal-title":"Acta Oncol."},{"issue":"9","key":"2021120108542821200_CIT0032","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1245\/s10434-016-5248-6","article-title":"Differentiating atypical parathyroid neoplasm from parathyroid cancer","volume":"23","author":"Christakis","year":"2016","journal-title":"Ann Surg Oncol."},{"issue":"4","key":"2021120108542821200_CIT0033","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.surg.2015.06.022","article-title":"The clinical importance of parathyroid atypia: is long-term surveillance necessary?","volume":"158","author":"McCoy","year":"2015","journal-title":"Surgery."},{"issue":"6","key":"2021120108542821200_CIT0034","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1002\/jso.24407","article-title":"Oncologic progress for the treatment of parathyroid carcinoma is needed","volume":"114","author":"Christakis","year":"2016","journal-title":"J Surg Oncol."},{"issue":"1","key":"2021120108542821200_CIT0035","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.abb.2011.11.003","article-title":"25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D","volume":"523","author":"Jones","year":"2012","journal-title":"Arch Biochem Biophys."},{"issue":"1-2","key":"2021120108542821200_CIT0036","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mce.2004.07.012","article-title":"Characterization of vitamin D-mediated induction of the CYP 24 transcription","volume":"226","author":"Tashiro","year":"2004","journal-title":"Mol Cell Endocrinol."},{"key":"2021120108542821200_CIT0037","first-page":"1429","article-title":"Pathology of the parathyroid glands","volume-title":"Surgical Pathology of the Head and Neck.","author":"Seethala","year":"2009"},{"issue":"2","key":"2021120108542821200_CIT0038","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0046-8177(95)90028-4","article-title":"Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining","volume":"26","author":"Abbona","year":"1995","journal-title":"Hum Pathol."},{"issue":"5","key":"2021120108542821200_CIT0039","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.stemcr.2019.03.010","article-title":"The PAF1c subunit CDC73 is required for mouse hematopoietic stem cell maintenance but displays leukemia-specific gene regulation","volume":"12","author":"Saha","year":"2019","journal-title":"Stem Cell Reports."},{"issue":"8","key":"2021120108542821200_CIT0040","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1136\/jmg.2005.032201","article-title":"Utilisation of a cryptic non-canonical donor splice site of the gene encoding PARAFIBROMIN is associated with familial isolated primary hyperparathyroidism","volume":"42","author":"Bradley","year":"2005","journal-title":"J Med Genet."},{"issue":"3","key":"2021120108542821200_CIT0041","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/humu.21188","article-title":"Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome and parathyroid tumors","volume":"31","author":"Newey","year":"2010","journal-title":"Hum Mutat."},{"issue":"2","key":"2021120108542821200_CIT0042","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/cen.12461","article-title":"Familial isolated primary hyperparathyroidism\/hyperparathyroidism-jaw tumour syndrome caused by germline gross deletion or point mutations of CDC73 gene in Chinese","volume":"81","author":"Kong","year":"2014","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"9","key":"2021120108542821200_CIT0043","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1530\/ERC-20-0149","article-title":"Genotype of CDC73 germline mutation determines risk of parathyroid cancer","volume":"27","author":"Li","year":"2020","journal-title":"Endocr Relat Cancer."},{"issue":"2","key":"2021120108542821200_CIT0044","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/cncr.22790","article-title":"Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis?","volume":"110","author":"Fernandez-Ranvier","year":"2007","journal-title":"Cancer."},{"issue":"12","key":"2021120108542821200_CIT0045","doi-asserted-by":"crossref","first-page":"1621","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."}],"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\/dgab452\/39001785\/dgab452.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/11\/e4565\/41378562\/dgab452.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/11\/e4565\/41378562\/dgab452.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:41:00Z","timestamp":1672533660000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/11\/e4565\/6307821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,22]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6,22]]},"published-print":{"date-parts":[[2021,10,21]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgab452","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,6,22]]}}}