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We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Materials and methods<\/jats:title>\n            <jats:p>We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17\/44 cases. Matched ccfDNA\/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05\u20130.19) vs. 0.05 (0.00-0.08) ng\/\u00b5l, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05\u20130.47) ng\/\u00b5l]. Within T-DNA, somatic variants were identified in 53% of adenomas: <jats:italic>PRKACA<\/jats:italic> in 2\/7 CPA-CS, <jats:italic>CTNNB1<\/jats:italic> in 3\/5 CPA-MACS and 1\/7 CPA-CS, <jats:italic>KCNJ5<\/jats:italic> in 2\/5 APA and <jats:italic>CACNA1D<\/jats:italic> in 1\/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s40618-025-02540-5","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T08:42:30Z","timestamp":1738399350000},"page":"1207-1216","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["ccfDNA analysis for the classification of adrenocortical adenomas"],"prefix":"10.1007","volume":"48","author":[{"given":"Mengjie","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Tourigny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Lippert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Crastin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Appenzeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Asia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Podstawka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasir S.","family":"Elhassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassiani","family":"Skordilis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Prete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5020-2071","authenticated-orcid":false,"given":"Cristina L.","family":"Ronchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"2540_CR1","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1093\/ejendo\/lvae022","volume":"189","author":"M Fassnacht","year":"2023","unstructured":"Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Pelsma I, Marina L, Lorenz K, Bancos I, Arlt W (2023) European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the study of adrenal tumors. 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