{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:59Z","timestamp":1787027759241,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,2]],"date-time":"2023-04-02T00:00:00Z","timestamp":1680393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Studies of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) shows divergence in frequency, disease definition, reporting of clinical characteristics and traces of selection bias. This is a nationwide population-based retrospective study of PHPT in MEN 2A, suggesting a representative frequency, with complete reporting and a strict PHPT definition. The Danish MEN 2A cohort 1930\u20132021 was used. Of 204 MEN 2A cases, 16 had PHPT, resulting in a frequency of 8% (CI, 5\u201312). Age-related penetrance at 50 years was 8% (CI, 4\u201315). PHPT was seen in the American Thyroid Association moderate (ATA-MOD) and high (ATA-H) risk groups in 62% and 38% of carriers, respectively. Median age at PHPT diagnosis was 45 years (range, 21\u201379). A total of 75% were asymptomatic and 25% were symptomatic. Thirteen underwent parathyroid surgery, resulting in a cure of 69%, persistence in 8% and recurrence in 23%. In this first study with a clear PHPT definition and no selection bias, we found a lower frequency of PHPT and age-related penetrance, but a higher age at PHPT diagnosis than often cited. This might be affected by the Danish RET p.Cys611Tyr founder effect. Our study corroborates that PHPT in MEN 2A is often mild, asymptomatic and is associated with both ATA-MOD and ATA-H variants. Likelihood of cure is high, but recurrence is not infrequent and can occur decades after surgery.<\/jats:p>","DOI":"10.3390\/cancers15072125","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T02:10:13Z","timestamp":1680487813000},"page":"2125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 2A in Denmark 1930\u20132021: A Nationwide Population-Based Retrospective Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-8196","authenticated-orcid":false,"given":"Magnus","family":"Holm","sequence":"first","affiliation":[{"name":"Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center North Denmark, Aalborg University Hospital, 9100 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5se","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-3355","authenticated-orcid":false,"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Copenhagen University Hospital, 2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Bay","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Rolighed","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Londero","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery, Aalborg University Hospital, 9100 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoffer","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Rask","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Zealand University Hospital, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Gaustadnes","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rossing","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Copenhagen University Hospital, 2100 Copenhagen, Denmark"},{"name":"Center for Genomic Medicine, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Godballe","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-3188","authenticated-orcid":false,"given":"Jes","family":"Mathiesen","sequence":"additional","affiliation":[{"name":"Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1093\/hmg\/2.7.851","article-title":"Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC","volume":"2","author":"Dou","year":"1993","journal-title":"Hum. 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