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. 2025 Jul 3:16:1463283.
doi: 10.3389/fendo.2025.1463283. eCollection 2025.

Association between sensitivity to thyroid hormone indices and frailty in the elderly: a cross-sectional study

Xinyu Qi  1 , Jia Fang  1 , Jiru Zhang  1 , Jihai Chen  1   2 , Daowen Zhang  1 , Runqing Shi  1 , Yusheng Zhang  1 , Lijun Wei  1 , Lu Yan  1 , Yunlu Sheng  1 , Guoxian Ding  1 , Xiaojun Ouyang  2 , Yu Duan  1
Affiliations

Association between sensitivity to thyroid hormone indices and frailty in the elderly: a cross-sectional study

Xinyu Qi et al. Front Endocrinol (Lausanne). .

Abstract

Objective: Frailty is a prevalent geriatric syndrome that affects several systems and lacks accurate evaluation indications. Previous studies on the association between thyroid function and frailty have contradicted. This study introduced the thyroid hormone sensitivity indices to analyze their connection with frailty and evaluate its usefulness in assessing frailty.

Methods: A total of 1030 Chinese elderly individuals were included. The FRAIL scale was utilized to assess the frailty status of subjects. The thyroid hormone sensitivity indices, including the following: Thyrotrophic Thyroxine Resistance Index (TT4RI), Thyroid Stimulating Hormone Index (TSHI), Thyroid Feedback Quantile-based Index (TFQI) and Free Triiodothyronine/Free Thyroxine (FT3/FT4), were calculated based on thyroid function. A multivariate logistic regression analysis assessed the association between frailty and these markers.

Results: The study findings indicated that frailty groups exhibited lower levels of FT3 and TSH compared to non-frailty groups. Additionally, the central sensitivity index of thyroid hormone [TFQI(FT3)] and the peripheral sensitivity index (FT3/FT4) were also lower in frailty groups. Following the adjustment for multiple variables, FT3 (OR=0.640, 95%CI: 0.534-0.768, p <0.001), TSHI (OR=0.829, 95%CI: 0.708-0.971, p =0.020), TFQI(FT3) (OR=0.358, 95%CI: 0.233-0.550, p <0.001) and FT3/FT4 (OR=0.006, 95%CI: 0.001-0.058, p <0.001) showed a negative connection with the score of FRAIL scale.

Conclusion: Serum FT3 and TSH declined in frail patients, whereas there was no alteration in serum FT4. Both the decrease of central sensitivity index of thyroid hormone, TSHI and TFQI(FT3), and peripheral sensitivity index, FT3/FT4, were associated with frailty assessed by FRAIL scale. Specific thyroid measures, especially FT3, TFQI(FT3) and FT3/FT4, would be served as easily measurable indications that are essential for evaluating frailty.

Keywords: aging; frailty; sarcopenia; thyroid function; thyroid hormone sensitivity indicators.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of thyroid function and thyroid hormone sensitivity index in elderly population (age≥60). (A) Comparison of FT3 among groups; (B) Comparison of FT4 among groups; (C) Comparison of TSH among groups; (D) Comparison of TSHI among groups; (E) Comparison of TT4RI among groups; (F) Comparison of TFQI(FT4) among groups; (G) Comparison of TFQI(FT3) among groups; (H) Comparison of FT3/FT4 among groups. H-test was used to compare and analyze the data differences among groups. If the difference among three groups was significant, further analysis was conducted to discern the differences between each pair of groups. The P-value represented the comparison result among three groups, along with the p-value for each pair of groups. *p <0.05, ***p <0.001. TSHI, Thyroid Stimulating Hormone Index; TT4RI, Thyrotrophic Thyroxine Resistance Index; TFQI, Thyroid Feedback Quantile-based Index; FT3/FT4, Free Triiodothyronine/Free thyroxine.
Figure 2
Figure 2
Comparison of thyroid function and thyroid hormone sensitivity index between octogenarians and beyond. (A) Comparison of FT3 among groups; (B) Comparison of FT4 among groups; (C) Comparison of TSH among groups; (D) Comparison of TSHI among groups; (E) Comparison of TT4RI among groups; (F) Comparison of TFQI(FT4) among groups; (G) Comparison of TFQI(FT3) among groups; (H) Comparison of FT3/FT4 among groups. H-test was used to compare and analyze the data differences among groups. If the difference among three groups was significant, further analysis was conducted to discern the differences between each pair of groups. The P-value represented the comparison result among three groups, along with the p-value for each pair of groups. *p <0.05, **p <0.01, ***p <0.001. TSHI, Thyroid Stimulating Hormone Index; TT4RI, Thyrotrophic Thyroxine Resistance Index; TFQI, Thyroid Feedback Quantile-based Index; FT3/FT4, Free Triiodothyronine/Free thyroxine.
Figure 3
Figure 3
Comparison of thyroid function and thyroid hormone sensitivity index in euthyroid subjects (age≥60). (A) Comparison of FT3 among groups; (B) Comparison of FT4 among groups; (C) Comparison of TSH among groups; (D) Comparison of TSHI among groups; (E) Comparison of TT4RI among groups; (F) Comparison of TFQI(FT4) among groups; (G) Comparison of TFQI(FT3) among groups; (H) Comparison of FT3/FT4 among groups. H-test was used to compare and analyze the data differences among groups. If the difference among three groups was significant, further analysis was conducted to discern the differences between each pair of groups. The P-value represented the comparison result among three groups, along with the p-value for each pair of groups. ***p <0.001. TSHI, Thyroid Stimulating Hormone Index; TT4RI, Thyrotrophic Thyroxine Resistance Index; TFQI, Thyroid Feedback Quantile-based Index; FT3/FT4, Free Triiodothyronine/Free thyroxine.
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