{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:12:21Z","timestamp":1778562741772,"version":"3.51.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The rising incidence of thyroid cancer (TC) underscores the need to identify modifiable risk factors for malignancy in patients with thyroid nodules. The role of circadian rhythm disruption (CRD), a pervasive modern lifestyle factor, in TC is poorly understood. We aimed to investigate the association between cumulative CRD and the risk of malignancy and aggressiveness in patients with thyroid nodules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a hospital-based, propensity score-matched study involving 2,541 patients who underwent thyroidectomy for thyroid nodules between 2016 and 2019.\u00a0A novel cumulative circadian rhythm disruption index (cCRDI), integrating sleep insufficiency, shift work history, chronotype\/mid-sleep timing, and dietary irregularity, was calculated from preoperative questionnaires. The primary outcome was the definitive postoperative histopathological diagnosis (benign vs. malignant). Propensity score matching (PSM) (1:1) was performed to balance baseline confounders (e.g., age, sex, BMI, TSH levels, and autoimmune status), yielding a cohort of 850 matched pairs (1,700 patients). Conditional logistic regression was used to assess the association between cCRDI and malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the matched cohort, a strong, dose-dependent relationship was observed. Compared to the No CRD group, the adjusted odds ratios (aOR) for malignancy were 1.58 (95% CI: 1.15\u20132.15) for Low CRD, 1.85 (95% CI: 1.30\u20132.62) for Moderate CRD, and 2.95 (95% CI: 2.05\u20134.25) for High CRD (\n                      <jats:italic>P<\/jats:italic>\n                      for trend &amp;lt; 0.001). Restricted cubic splines confirmed a non-linear association with accelerating risk at higher cCRDI scores (\n                      <jats:italic>P<\/jats:italic>\n                      for non-linearity = 0.008). Crucially, increasing CRD severity was independently associated with aggressive clinicopathological features, including multifocality, extrathyroidal extension (ETE), and a dramatic increase in lymph node metastasis (LNM) (69.4% in High CRD vs. 29.3% in No CRD,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). High CRD remained the strongest independent predictor for LNM in multivariable analysis (aOR = 4.21, 95% CI: 2.90\u20136.10,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cumulative CRD is independently associated with both the presence of malignancy and the aggressive progression of TC in patients with thyroid nodules. Assessing a patient\u2019s circadian health might have potential utility as a novel, modifiable factor for risk stratification and may underscore the importance of lifestyle interventions in the clinical management of thyroid nodules.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1832788","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:30:08Z","timestamp":1778560208000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between circadian rhythm disruption and the risk of malignancy in patients with thyroid nodules: a propensity score-matched study"],"prefix":"10.3389","volume":"17","author":[{"given":"Pengfei","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Thyroid Surgery, Binzhou Medical University Hospital","place":["Binzhou, Shandong, China"]},{"name":"Medical Integration and Practice Center, Shandong 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