{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T18:41:53Z","timestamp":1769280113956,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Graves\u2019 disease (GD) and Thyroid Eye Disease (TED) are autoimmune disorders characterized by significant heterogeneity in treatment response. Up to 50% of GD patients relapse after antithyroid drug (ATD) withdrawal, and a substantial portion of TED patients (20\u201350%) are resistant to first-line glucocorticoid (GC) therapy. This review evaluates the current evidence on epigenetic modifications as predictive biomarkers to guide personalized treatment. We synthesized recent findings (up to 2025) from PubMed, focusing on DNA methylation and microRNAs (miRNAs). For GD, ATD relapse risk is linked to a persistent \u201cepigenetic memory\u201d in T cells, notably the hypomethylation of Th17-associated genes. Circulating miRNA signatures, including miR-346, miR-23b-5p, and miR-92a-3p, also show promise in predicting remission. For TED, GC sensitivity is strongly correlated with specific circulating miRNAs. High pre-treatment levels of miR-146a predict a positive response (100% positive predictive value), while low levels of miR-224-5p predict non-responsiveness. While DNA methylation is confirmed in TED pathogenesis, its predictive role is unstudied. Major research gaps persist, particularly the near-total absence of data on histone modifications as predictive markers and the lack of epigenetic predictors for new biologics treatments, which currently rely on genetic or pharmacokinetic markers. Epigenetic biomarkers represent a promising frontier for stratifying patients and optimizing therapeutic strategies in Graves\u2019 autoimmunity.<\/jats:p>","DOI":"10.3390\/ijms27021116","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Genome: Can Epigenetics Forecast Therapeutic Success in Graves\u2019 Disease and Thyroid Eye Disease?"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-4339","authenticated-orcid":false,"given":"Jacopo","family":"Manso","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3147-9942","authenticated-orcid":false,"given":"Dario","family":"Sardone","sequence":"additional","affiliation":[{"name":"Department of Medical Surgical and Health Sciences, Cattinara Teaching Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9889-3887","authenticated-orcid":false,"given":"Vincenzo","family":"Marotta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, \u201cScuola Medica Salernitana\u201d, University of Salerno, 84084 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0131-8681","authenticated-orcid":false,"given":"Antonio Stefano","family":"Salcuni","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Cipri","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Maria","family":"Sciannimanico","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Piva","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-3152","authenticated-orcid":false,"given":"Maria","family":"Carpentieri","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-4417","authenticated-orcid":false,"given":"Alberto","family":"Falchetti","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-9785","authenticated-orcid":false,"given":"Fabio","family":"Vescini","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Oncology Area Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/epi.27473","article-title":"Non-coding RNAs as direct and indirect modulators of epigenetic regulation","volume":"9","author":"Peschansky","year":"2014","journal-title":"Epigenetics"},{"key":"ref_2","first-page":"970607","article-title":"Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation","volume":"2014","author":"Safaralizadeh","year":"2014","journal-title":"Int. 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