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However, 10\u201330% of patients with MEN1-like features lack identifiable\n                    <jats:italic>MEN1<\/jats:italic>\n                    mutations and are classified as phenocopies. This retrospective multicenter study, conducted across 10 Italian referral centers, aimed to characterize the main clinical features of phenocopies. Among 240 patients evaluated for suspected MEN1 over five years, 175 (mean age 43.2\u2009\u00b1\u200919.7; 101 females) had genetically confirmed MEN1, while 65 (27%; mean age 59.9\u2009\u00b1\u200911.6; 44 females) were identified as phenocopies. Of these, 46 (70.7%) were also negative for\n                    <jats:italic>CDKN1B<\/jats:italic>\n                    mutations, confirming the rarity of MEN4. Phenocopies were diagnosed one to two decades later than MEN1 patients (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). PHPT was the most frequent manifestation in both groups (80% of phenocopies vs. 81% of MEN1), but tumor associations differed significantly between groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001): 41% of MEN1 patients showed the classic triad, compared to only 1% of phenocopies; PHPT with NETs was more common in MEN1 (32%), whereas PHPT with PitNETs occurred more often in phenocopies (54%), reflecting patterns of sporadic tumors. Notably, 11% of phenocopies had a first-degree relative with MEN1-related diseases, and 51% had a personal or family history of cancer. In conclusion, MEN1 phenocopies are relatively common and represent a clinical challenge. Given their distinct features and familial backgrounds, an extended genetic panel should be offered to these patients together with periodical screening of MEN1-related disease.\n                  <\/jats:p>","DOI":"10.1007\/s40618-025-02743-w","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:39:54Z","timestamp":1762947594000},"page":"573-584","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The clinical challenge of MEN1 phenocopies: insights from a multicentric national retrospective study"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-684X","authenticated-orcid":false,"given":"Rosaria M.","family":"Ruggeri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-3651","authenticated-orcid":false,"given":"Elio","family":"Benevento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7363-571X","authenticated-orcid":false,"given":"Iderina","family":"Hasballa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-7618","authenticated-orcid":false,"given":"Erika Maria","family":"Grossrubatscher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-5803","authenticated-orcid":false,"given":"Roberta","family":"Modica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5957-3247","authenticated-orcid":false,"given":"Manuela","family":"Albertelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Golisano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-8558","authenticated-orcid":false,"given":"Vito","family":"Guarnieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9968-8172","authenticated-orcid":false,"given":"Flavia","family":"Pugliese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8088-4947","authenticated-orcid":false,"given":"Valentina","family":"Guarnotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6045-2992","authenticated-orcid":false,"given":"Simona","family":"Jaafar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-2141","authenticated-orcid":false,"given":"Andrea","family":"Lania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7021-9860","authenticated-orcid":false,"given":"Antonio","family":"Prinzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Zanata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8408-7796","authenticated-orcid":false,"given":"Maria Chiara","family":"Zatelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4049-2559","authenticated-orcid":false,"given":"Annamaria","family":"Colao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9324-3946","authenticated-orcid":false,"given":"Antongiulio","family":"Faggiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of NIKE Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"issue":"2","key":"2743_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1210\/endrev\/bnaa031","volume":"42","author":"ML Brandi","year":"2021","unstructured":"Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV (2021) Multiple endocrine neoplasia type 1: latest insights. 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Local Ethics Research Committee approval was obtained. No animals were used for this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants, or animals"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}