{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:27:16Z","timestamp":1792592836174,"version":"4.5.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative (&lt;50 IU\/mL) and with TSH levels within the euthyroid range (\u22650.5 and \u22645.0 mUI\/mL) participating in the nationwide study Di@bet.es (2008\u20132010).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 231 deaths were recorded during an average follow-up of 7.3 years. Compared with the category with the highest sensitivity to free thyroxine (TFQI \u2264 p5) (reference), the relative risk of mortality in the categories with TFQI &gt; p5 and \u2264p25; &gt;p25 and \u2264p50; &gt;p50 and \u2264p75; &gt;p75 and \u2264p95 and &gt;p95 were 1.01, (0.47\u20132.19), 1.42 (0.68\u20132.97), 1.54 (0.74\u20133.22), 1.47 (0.70\u20133.11) and 2.61 (1.16\u20135.89), respectively (<jats:italic>P<\/jats:italic> for trend 0.003). The association remained significant after multivariate adjustment of the data (<jats:italic>P<\/jats:italic> for trend 0.017).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>A thyroid hormone resistance index focused on deviations of the average pituitary response to thyroid hormones may be associated with all-cause mortality independently of other conventional risk factors and comorbidities.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0640","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T17:31:23Z","timestamp":1636047083000},"page":"95-103","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":23,"title":["Thyroid hormone resistance index and mortality in euthyroid subjects: Di@bet.es study"],"prefix":"10.1093","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5645-0113","authenticated-orcid":true,"given":"Silvia Patricia","family":"Alonso","sequence":"first","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Vald\u00e9s","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Maldonado-Araque","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Lago","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Ocon","sequence":"additional","affiliation":[{"name":"3UGC de Laboratorio (Bioqu\u00edmica), Hospital Regional Universitario de M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Calle","sequence":"additional","affiliation":[{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"4Department of Endocrinology and Nutrition, Hospital Universitario S. Carlos de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"5Hospital Universitario Cruces, BioCruces Bizkaia, UPV\/EHU, Barakaldo, Spain"},{"name":"6Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-9712","authenticated-orcid":true,"given":"El\u00edas","family":"Delgado","sequence":"additional","affiliation":[{"name":"6Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"7Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias\/University of Oviedo, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edelmiro","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"6Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"7Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias\/University of Oviedo, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Franch-Nadal","sequence":"additional","affiliation":[{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"8EAP Raval Sud, Institut Catal\u00e0 de la Salut, Red GEDAPS, Primary Care, Unitat de Suport a la Recerca (IDIAP \u2013 Fundaci\u00f3 Jordi Gol), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Gaztambide","sequence":"additional","affiliation":[{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"6Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"9Department of Endocrinology and Nutrition, Hospital Universitario Cruces \u2013 BioCruces Bizkaia \u2013 UPV-EHU, Baracaldo, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Girb\u00e9s","sequence":"additional","affiliation":[{"name":"10Diabetes Unit, Hospital Arnau de Vilanova, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Chaves","sequence":"additional","affiliation":[{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"11Genomic Studies and Genetic Diagnosis Unit, Fundaci\u00f3n de Investigaci\u00f3n del Hospital Cl\u00ednico de Valencia-INCLIVA, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Garcia-Serrano","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Garcia-Escobar","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Carlos","family":"Fernandez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Olveira","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Colomo","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Rojo-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Nutrition, Hospital Regional Universitario de M\u00e1laga\/Universidad de M\u00e1laga, Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga-IBIMA, M\u00e1laga, Spain"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of 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