{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:46:52Z","timestamp":1760060812526,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clocks &amp; Sleep"],"abstract":"<jats:p>Background: Circadian Syndrome (CircS) encompasses a range of cardiometabolic risk factors that contribute to an increased susceptibility to cardiovascular diseases and type 2 diabetes. Understanding the factors that underpin CircS is essential. This study primarily aims to examine the association between hypothyroidism and CircS in adults. A secondary analysis compares this association with that between hypothyroidism and Metabolic Syndrome (MetS). Additionally, the dose\u2013response relationship between serum free thyroxine (FT4) levels and CircS probability is explored. Methods: This cross-sectional study includes 4050 National Health and Nutrition Examination Survey (NHANES) participants (2007\u20132012). Hypothyroidism was classified into (1) drug-managed, (2) non-drug-managed (NDM) primary, and (3) NDM central hypothyroidism, based on self-reported medication use and serum TSH\/FT4 levels. CircS was defined as having \u22655 of its eight components, including MetS criteria, depression, short sleep, and non-alcoholic fatty liver disease. Results: Our results showed that hypothyroidism was significantly associated with CircS (OR: 1.58, 95% CI 1.26\u20131.98) and MetS (OR: 1.19, 95% CI 1.01\u20131.42). An inverse, non-linear relationship between serum FT4 levels and the probability of CircS was observed. Conclusions: The results underscore a significant association between hypothyroidism and CircS and MetS, with FT4 levels inversely related to CircS probability. These findings highlight hypothyroidism\u2019s potential role in CircS pathogenesis and prevention.<\/jats:p>","DOI":"10.3390\/clockssleep7040052","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:43:12Z","timestamp":1758706992000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Cross-Sectional Association Between Hypothyroidism and Circadian Syndrome: Insights from NHANES 2007\u20132012"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1543-8287","authenticated-orcid":false,"given":"Ahmed","family":"Arabi","sequence":"first","affiliation":[{"name":"College of Medicine, Qatar University (QU) Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3621-0518","authenticated-orcid":false,"given":"Humam Emad","family":"Rajha","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University (QU) Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama","family":"Alkeilani","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University (QU) Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5655-7367","authenticated-orcid":false,"given":"Ahmad","family":"Hamdan","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University (QU) Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dima","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University (QU) Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giridhara R.","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Population Medicine, College of Medicine, Qatar University (QU) Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Arabi, A., Nasrallah, D., Mohsen, S., Abugharbieh, L., Al-Hashimi, D., AlMass, S., Albasti, S., Al-Ajmi, S.A., Khan, M.N., and Zughaier, S.M. (2024). Association between Serum Vitamin D Status and Circadian Syndrome: A Cross-Sectional Study. Nutrients, 16.","DOI":"10.3390\/nu16132111"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41583-018-0026-z","article-title":"Generation of circadian rhythms in the suprachiasmatic nucleus","volume":"19","author":"Hastings","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41574-018-0142-x","article-title":"The arrival of circadian medicine","volume":"15","author":"Panda","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1113\/JP286449","article-title":"Hypothyroidism alters the rhythmicity of the central clock, body temperature and metabolism: Evidence of Bmal1 transcriptional regulation by T3","volume":"602","author":"Emrich","year":"2024","journal-title":"J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/07420528.2017.1388253","article-title":"Repercussions of hypo and hyperthyroidism on the heart circadian clock","volume":"35","author":"Young","year":"2018","journal-title":"Chronobiol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pingitore, A., Gaggini, M., Mastorci, F., Sabatino, L., Cordiviola, L., and Vassalle, C. (2024). Metabolic Syndrome, Thyroid Dysfunction, and Cardiovascular Risk: The Triptych of Evil. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910628"},{"key":"ref_8","first-page":"e67851","article-title":"A Cross-Sectional Study on the Prevalence of Subclinical Hypothyroidism in Metabolic Syndrome Patients at a Tertiary Care Hospital","volume":"16","author":"Lakhani","year":"2024","journal-title":"Cureus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"717","DOI":"10.4103\/aam.aam_25_24","article-title":"Hypothyroidism in Metabolic Syndrome","volume":"23","author":"Verma","year":"2024","journal-title":"Ann. Afr. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100279","DOI":"10.1016\/j.cpnec.2024.100279","article-title":"Association between depression and anxiety disorders with euthyroid Hashimoto\u2019s thyroiditis: A systematic review and meta-analysis","volume":"20","author":"Wang","year":"2024","journal-title":"Compr. Psychoneuroendocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Soares De Oliveira, L., and Ritter, M.J. (2025). Thyroid hormone and the Liver. Hepatol. Commun., 9.","DOI":"10.1097\/HC9.0000000000000596"},{"key":"ref_12","first-page":"e69855","article-title":"Evaluating the Spectrum of Sleep Abnormalities in Patients With Primary Hypothyroidism","volume":"16","author":"Acharya","year":"2024","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40842-016-0021-0","article-title":"Thyroid dysfunction in metabolic syndrome patients and its relationship with components of metabolic syndrome","volume":"2","author":"Khatiwada","year":"2016","journal-title":"Clin. Diabetes Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1530\/EJE-12-0375","article-title":"Thyroid function and the metabolic syndrome in older persons: A population-based study","volume":"168","author":"Heima","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"He, J., Lai, Y., Yang, J., Yao, Y., Li, Y., Teng, W., and Shan, Z. (2021). The Relationship Between Thyroid Function and Metabolic Syndrome and Its Components: A Cross-Sectional Study in a Chinese Population. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.661160"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S332","DOI":"10.4103\/2230-8210.104079","article-title":"Hypothyroidism in metabolic syndrome","volume":"16","author":"Kota","year":"2012","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3109\/07435800.2015.1108332","article-title":"Subclinical hypothyroidism and the risk of metabolic syndrome: A meta-analysis of observational studies","volume":"41","author":"Yang","year":"2016","journal-title":"Endocr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1507\/endocrj.EJ20-0796","article-title":"The association between subclinical hypothyroidism and metabolic syndrome: An update meta-analysis of observational studies","volume":"68","author":"Ding","year":"2021","journal-title":"Endocr. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1001\/jamapsychiatry.2021.2506","article-title":"Association of Hypothyroidism and Clinical Depression: A Systematic Review and Meta-analysis","volume":"78","author":"Bode","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000454920","article-title":"Nonalcoholic Fatty Liver Disease Is Not Associated with Thyroid Hormone Levels and Hypothyroidism: A Systematic Review and Meta-Analysis","volume":"6","author":"Jaruvongvanich","year":"2017","journal-title":"Eur. Thyroid. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8102","DOI":"10.3748\/wjg.v20.i25.8102","article-title":"Non-alcoholic fatty liver disease and thyroid dysfunction: A systematic review","volume":"20","author":"Eshraghian","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"He, W., An, X., Li, L., Shao, X., Li, Q., Yao, Q., and Zhang, J.-a. (2017). Relationship between Hypothyroidism and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00335"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e25738","DOI":"10.1097\/MD.0000000000025738","article-title":"The relationship between non-alcoholic fatty liver disease and hypothyroidism: A systematic review and meta-analysis","volume":"100","author":"Zeng","year":"2021","journal-title":"Medicine"},{"key":"ref_24","first-page":"147","article-title":"Study of Insulin Resistance in Subclinical Hypothyroidism","volume":"4","author":"Vyakaranam","year":"2014","journal-title":"Int. J. Health Sci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10067","DOI":"10.1073\/pnas.1633737100","article-title":"Selective thyroid hormone receptor-beta activation: A strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability","volume":"100","author":"Grover","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"725829","DOI":"10.3389\/fendo.2021.725829","article-title":"Thyroid Dysfunction and Sleep Disorders","volume":"12","author":"Green","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejim.2024.03.013","article-title":"The interplay between subclinical hypothyroidism and poor sleep quality: A systematic review","volume":"126","author":"Teliti","year":"2024","journal-title":"Eur. J. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1126\/science.280.5369.1564","article-title":"Role of the CLOCK protein in the mammalian circadian mechanism","volume":"280","author":"Gekakis","year":"1998","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1073\/pnas.95.10.5474","article-title":"The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors","volume":"95","author":"Hogenesch","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"915139","DOI":"10.3389\/fendo.2022.915139","article-title":"Emerging Insight Into the Role of Circadian Clock Gene BMAL1 in Cellular Senescence","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3109\/07853890.2014.914808","article-title":"Circadian gene variants in cancer","volume":"46","author":"Kettner","year":"2014","journal-title":"Ann Med"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.neulet.2006.08.057","article-title":"Thyroidectomy alters the daily pattern of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats","volume":"407","author":"Amir","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0031-9384(88)90256-9","article-title":"Effects of thyroidectomy, parathyroidectomy and lithium on circadian wheelrunning in rats","volume":"42","author":"Schull","year":"1988","journal-title":"Physiol. Behav."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41574-019-0237-z","article-title":"Interconnection between circadian clocks and thyroid function","volume":"15","author":"Ikegami","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/EDE.0b013e3181577511","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration","volume":"18","author":"Vandenbroucke","year":"2007","journal-title":"Epidemiology"},{"key":"ref_36","unstructured":"Johnson, C.L., Paulose-Ram, R., Ogden, C.L., Carroll, M.D., Kruszon-Moran, D., Dohrmann, S.M., and Curtin, L.R. (2013). National health and nutrition examination survey: Analytic guidelines, 1999\u20132010. Vital Health Stat. 2, 1\u201324."},{"key":"ref_37","unstructured":"Ross, D.S. (2024). Diagnosis of and Screening for Hypothyroidism in Nonpregnant Adults, UpToDate."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: Validity of a brief depression severity measure","volume":"16","author":"Kroenke","year":"2001","journal-title":"J. Gen. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Akbar, Z., and Shi, Z. (2023). Dietary Patterns and Circadian Syndrome among Adults Attending NHANES 2005\u20132016. Nutrients, 15.","DOI":"10.3390\/nu15153396"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12986-024-00892-y","article-title":"Association of serum magnesium and calcium with metabolic syndrome: A cross-sectional study from the Qatar-biobank","volume":"22","author":"Alsheikh","year":"2025","journal-title":"Nutr. Metab."},{"key":"ref_41","unstructured":"(2024, March 22). Drinking Levels Defined, Available online: https:\/\/www.niaaa.nih.gov\/alcohol-health\/overview-alcohol-consumption\/moderate-binge-drinking."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41598-023-27474-x","article-title":"Family income and cardiovascular disease risk in American adults","volume":"13","author":"Minhas","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_43","unstructured":"(2024, March 22). Developing the Healthy Eating Index, Available online: https:\/\/epi.grants.cancer.gov\/hei\/developing.html#:~:text=For%20the%20first%20time%2C%20the,2%20and%20older%3B%20and%20the."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e45776","DOI":"10.2196\/45776","article-title":"Association Between Joint Physical Activity and Dietary Quality and Lower Risk of Depression Symptoms in US Adults: Cross-sectional NHANES Study","volume":"9","author":"Liang","year":"2023","journal-title":"JMIR Public Health Surveill."},{"key":"ref_45","unstructured":"(WHO), W.H.O. (2024, December 26). Global Physical Activity Questionnaire (GPAQ). Available online: https:\/\/www.who.int\/publications\/m\/item\/global-physical-activity-questionnaire."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/hep.24105","article-title":"Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: An updated meta-analysis","volume":"53","author":"Lin","year":"2011","journal-title":"Hepatology"},{"key":"ref_47","unstructured":"Ross, A.C., Taylor, C.L., Yaktine, A.L., and Del Valle, H.B. (2011). The National Academies Collection: Reports funded by National Institutes of Health. Dietary Reference Intakes for Calcium and Vitamin D, National Academy of Sciences. National Academies Press (US) Copyright \u00a9 2011."}],"container-title":["Clocks &amp; Sleep"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2624-5175\/7\/4\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:43Z","timestamp":1760035723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2624-5175\/7\/4\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["clockssleep7040052"],"URL":"https:\/\/doi.org\/10.3390\/clockssleep7040052","relation":{},"ISSN":["2624-5175"],"issn-type":[{"type":"electronic","value":"2624-5175"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}