{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:09:45Z","timestamp":1788930585521,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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 regulation and secretion of hormones in the endocrine system change with aging. While these changes may influence age-related disease risks, the role of hypothalamic-pituitary-thyroid (HPT) axis sensitivity in metabolic and cardiovascular health remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 13,646 participants (6,221 males, 7,425 females). Metabolic (BMI, SUA, FPG, lipoproteins) and cardiovascular (ECG, CK-MB, NT-proBNP) indices were measured. Multivariable logistic regression adjusted for age (per 10-year increment), sex, and outcome-specific confounders. Nonlinear relationships between age and TFQI were analyzed using restricted cubic splines (RCS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>RCS analysis revealed a significant age-dependent decline in TFQI-fT3 values, with an inflection point at 48 years (p&amp;lt;0.001); TFQI-fT4 showed a similar but attenuated trend. For metabolic outcomes, increased fT3 sensitivity (TFQI-fT3 Q1) was associated with lower MetS risk in older adults (&amp;gt;48 years) (OR 0.79, 95% CI 0.65-0.97, p=0.023), whereas no significant association was observed in younger adults (\u226448 years) (all p&amp;gt;0.05). For cardiovascular outcomes, higher fT3 sensitivity was associated with reduced risk of abnormal ST segments in both age groups (younger: OR 0.57, 95% CI 0.32-0.97, p=0.046; older: OR 0.68, 95% CI 0.48-0.95, p=0.027). Conversely, decreased fT4 sensitivity (TFQI-fT4 Q4) specifically increased abnormal ST-segment risk in older adults (OR 1.43, 95% CI 1.04-1.96, p=0.025), with no significant effect in younger adults (OR 1.11, 95% CI 0.65-1.82, p=0.693).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Enhanced HPT axis sensitivity to fT3 increased with age (inflection point at 48 years in this study) and was associated with a lower prevalence of metabolic syndrome (in &amp;gt;48-year-olds) and ST-segment abnormalities (all adults).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1857191","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:45:19Z","timestamp":1788929119000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-related changes in HPT axis sensitivity and their associations with metabolic and cardiovascular health: a cross-sectional, Chinese nationwide study"],"prefix":"10.3389","volume":"17","author":[{"given":"Lei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runqing","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1210\/er.2018-00163","article-title":"Thyroid dysfunction and diabetes mellitus: Two closely associated disorders","volume":"40","author":"Biondi","year":"2019","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.08.001","article-title":"NAFLD and thyroid function: Pathophysiological and therapeutic considerations","volume":"33","author":"Hatziagelaki","year":"2022","journal-title":"Trends Endocrinol Metabolism: TEM"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312797","article-title":"Hypothyroidism-associated dyslipidemia: Potential molecular mechanisms leading to NAFLD","volume":"22","author":"Mavromati","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.117.028753","article-title":"Thyroid function within the normal range, subclinical hypothyroidism, and the risk of atrial fibrillation. 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