ArticleFrontiers in endocrinology2026
Age-related changes in HPT axis sensitivity and their associations with metabolic and cardiovascular health: a cross-sectional, Chinese nationwide study.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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). Result: RCS analysis revealed a significant age-dependent decline in TFQI-fT3 values, with an inflection point at 48 years (p<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 (>48 years) (OR 0.79, 95% CI 0.65-0.97, p=0.023), whereas no significant association was observed in younger adults (≤48 years) (all p>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). Conclusion: 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 >48-year-olds) and ST-segment abnormalities (all adults).
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