{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:37:26Z","timestamp":1782970646827,"version":"3.54.5"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013958","name":"Sykehuset Telemark","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013958","id-type":"DOI","asserted-by":"publisher"}]}],"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>Patients with Hashimoto\u2019s thyroiditis frequently experience fatigue and impaired health-related quality of life (HRQOL) despite biochemical euthyroidism, suggesting that immune-mediated mechanisms beyond thyroid hormone deficiency contribute to symptom generation. The role of specific inflammatory mediators - including interleukin-1 receptor antagonist (IL-1Ra), heat shock protein 90\u03b1 (HSP90\u03b1), interleukin-6 (IL-6), tumor necrosis factor-\u03b1 (TNF-\u03b1), and anti-TPO antibodies - in relation to patient-reported outcomes (PROMs) has not been systematically examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a cross-sectional study of 36 euthyroid patients with confirmed Hashimoto\u2019s thyroiditis, serum\/plasma levels of IL-1Ra, HSP90\u03b1, IL-6, and TNF-\u03b1 were measured alongside anti-TPO. PROMs included the SF-36 General Health subscale (inverted; iGH), the Fatigue Visual Analog Scale (fVAS), and the Fatigue Severity Scale (FSS). Spearman correlations, univariable and multivariable linear regression, and principal component analysis (PCA) were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort displayed severe fatigue at baseline (median fVAS 85, FSS 6.7, SF-36 GH 16). IL-1Ra was the most consistent biomarker correlate of symptom burden, independently associated with poorer general health and more fatigue across all regression models. HSP90\u03b1 showed an inverse and independent association with fatigue in multivariable models, suggesting a potentially protective role. IL-6 contributed in correlation analysis only, while TNF-\u03b1 and anti-TPO were not significantly associated with any PROM in any analytical approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IL-1Ra and HSP90\u03b1, but not anti-TPO, are independently associated with fatigue and general health in euthyroid Hashimoto\u2019s thyroiditis, pointing to IL-1 pathway activity as associated with symptom burden and potentially playing a key role in this condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1862441","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:24:55Z","timestamp":1782966295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin\u22121 receptor antagonist and heat shock protein 90alfa are independently associated with fatigue and general health in euthyroid Hashimoto\u2019s thyroiditis"],"prefix":"10.3389","volume":"17","author":[{"given":"Roald","family":"Omdal","sequence":"first","affiliation":[{"name":"Research Department, Stavanger University Hospital","place":["Stavanger, Norway"]},{"name":"Department of Clinical Science, University of Bergen","place":["Bergen, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tore","family":"Grimstad","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen","place":["Bergen, Norway"]},{"name":"Department of Internal Medicine, Stavanger University Hospital","place":["Stavanger, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grete","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Stavanger University Hospital","place":["Stavanger, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Terje","family":"Kval\u00f8y","sequence":"additional","affiliation":[{"name":"Research Department, Stavanger University Hospital","place":["Stavanger, Norway"]},{"name":"Department of Mathematics and Physics, University of Stavanger","place":["Stavanger, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Medicine, \u00d8stfold Hospital Trust","place":["Kalnes, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurens C.","family":"Reitsma","sequence":"additional","affiliation":[{"name":"Department of Surgery, Akershus University Hospital","place":["L\u00f8renskog, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomm","family":"Bernklev","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geir","family":"Hoff","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]},{"name":"Department of Research and Innovation, Telemark Hospital","place":["Skien, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.37766\/inplasy2025.3.0049","article-title":"A scoping review on the prevalence of Hashimoto's thyroiditis and the possible associated factors","volume":"13","author":"Vargas-Uricoechea","year":"2025","journal-title":"Med Sci (Basel)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2003.01681.x","article-title":"Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease","volume":"58","author":"Demers","year":"2003","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2042","article-title":"Antithyroperoxidase antibody-dependent cytotoxicity in autoimmune thyroid disease","volume":"93","author":"Rebuffat","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","article-title":"Thyroid peroxidase and thyroglobulin antibodies","volume-title":"Autoantibodies","author":"Latrofa","year":"2013"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0191","article-title":"Hashimoto's thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter","volume":"21","author":"Ott","year":"2011","journal-title":"Thyroid"},{"key":"B6","doi-asserted-by":"publisher","first-page":"27902","DOI":"10.1038\/s41598-024-78938-7","article-title":"Thyroid antibodies in Hashimoto's thyroiditis patients are positively associated with inflammation and multiple symptoms","volume":"14","author":"Li","year":"2024","journal-title":"Sci Rep"},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbi.2012.01.006","article-title":"Thyroid peroxidase antibody positivity is associated with symptomatic distress in patients with Hashimoto's thyroiditis","volume":"26","author":"Mussig","year":"2012","journal-title":"Brain Behavior Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2021.100101","article-title":"Persisting symptoms in patients with Hashimoto's disease despite normal thyroid hormone levels: does thyroid autoimmunity play a role? A systematic review","volume":"4","author":"Groenewegen","year":"2021","journal-title":"J Transl Autoimmun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-10394-5","article-title":"Physical fatigability and muscle pain in patients with Hashimoto thyroiditis","volume":"268","author":"Jordan","year":"2021","journal-title":"J Neurol"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1046\/j.1365-2265.2002.01654.x","article-title":"Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study","volume":"57","author":"Saravanan","year":"2002","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13113082","article-title":"Evaluation of health-related quality of life in patients with euthyroid Hashimoto's thyroiditis under long-term levothyroxine therapy: a prospective case-control study","volume":"13","author":"Tabakoglu","year":"2024","journal-title":"J Clin Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7326\/m18-0284","article-title":"Thyroidectomy versus medical management for euthyroid patients with Hashimoto disease and persisting symptoms: a randomized trial","volume":"170","author":"Guldvog","year":"2019","journal-title":"Ann Intern Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102649","article-title":"Hashimoto's thyroiditis: an update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential Malignant transformation","volume":"19","author":"Ralli","year":"2020","journal-title":"Autoimmun Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.06.011","article-title":"Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications","author":"Bower","year":"2013","journal-title":"Brain Behavior Immun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1330386","article-title":"Level of IL-6, TNF, and IL-1beta and age-related diseases: a systematic review and meta-analysis","volume":"15","author":"Tylutka","year":"2024","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s10020-023-00679-6","article-title":"High mobility group box 1 and a network of other biomolecules influence fatigue in patients with Crohn's disease","volume":"29","author":"Kvivik","year":"2023","journal-title":"Mol Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12974-017-0796-7","article-title":"Interleukin-1 as a mediator of fatigue in disease: a narrative review","volume":"14","author":"Roerink","year":"2017","journal-title":"J Neuroinflamm"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-004-0463-z","article-title":"The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis--a pilot study","volume":"25","author":"Omdal","year":"2005","journal-title":"Rheumatol Int"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23112846","article-title":"Heat shock proteins as immunomodulants","volume":"23","author":"Zininga","year":"2018","journal-title":"Molecules"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1177\/1753425916633236","article-title":"Heat shock proteins and chronic fatigue in primary Sjogren's syndrome","volume":"22","author":"Bardsen","year":"2016","journal-title":"Innate Immun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/03000605241280049","article-title":"Evaluation of systemic inflammation markers in patients with Hashimoto's thyroiditis","volume":"52","author":"Bozdag","year":"2024","journal-title":"J Int Med Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1037\/t06708-000","article-title":"The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection","volume":"30","author":"Ware","year":"1992","journal-title":"Med Care"},{"key":"B23","article-title":"The prevalence and meaning of fatigue in rheumatic disease","volume":"23","author":"Wolfe","year":"1996","journal-title":"J Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7551\/mitpress\/2967.003.0008","article-title":"The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus","volume":"46","author":"Krupp","year":"1989","journal-title":"Arch Neurol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-017-1684-4","article-title":"Norwegian reference values for the Short-Form Health Survey 36: development over time","volume":"27","author":"Jacobsen","year":"2018","journal-title":"Qual Life Research: Int J Qual Life Aspects Treatment Care Rehabil"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0277-8","article-title":"The IL-1 family of cytokines and receptors in rheumatic diseases","volume":"15","author":"Dinarello","year":"2019","journal-title":"Nat Rev Rheumatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2006.09.006","article-title":"Twenty years of research on cytokine-induced sickness behavior","volume":"21","author":"Dantzer","year":"2007","journal-title":"Brain Behavior Immun"},{"key":"B28","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s13075-020-02344-3","article-title":"High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab","volume":"22","author":"Strand","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B29","article-title":"Serum concentrations of leptin, adiponectin, and interleukin-6 in postmenopausal women with Hashimoto's thyroiditis","volume":"61","author":"Sieminska","year":"2010","journal-title":"Endokrynol Pol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1213448","article-title":"Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders","volume":"14","author":"Gonzalez Caldito","year":"2023","journal-title":"Front Immunol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1862441\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:24:56Z","timestamp":1782966296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1862441\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":30,"alternative-id":["10.3389\/fendo.2026.1862441"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1862441","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1862441"}}