# Impaired sensitivity to thyroid hormones is associated with frailty in older patients with cardiometabolic disease

## TL;DR

This study finds that reduced sensitivity to thyroid hormones is linked to frailty in older patients with heart and metabolic diseases.

## Contribution

The study identifies specific thyroid hormone sensitivity indices as independent predictors of frailty in older cardiometabolic patients.

## Key findings

- Lower fT3/fT4 and higher TFQI were associated with frailty in older patients.
- fT3/fT4 independently predicted frailty after adjusting for multiple factors.
- fT3/fT4 showed better discriminative ability than other thyroid-related measures.

## Abstract

It is unclear how impaired peripheral and central sensitivity to thyroid hormones relates to frailty. In this cross-sectional study, we investigated whether these indices were associated with the prevalence of frailty in older patients with cardiometabolic disease.

A total of 637 older patients with cardiometabolic disease who visited an outpatient clinic and were evaluated for thyroid function and frailty indices were included in this analysis. The free triiodothyronine/free thyroxine ratio (fT3/fT4) and Thyroid Feedback Quantile-based Index (TFQI) were measured as peripheral and central sensitivity to thyroid hormones, respectively. Using the Mann–Whitney U test and multivariate logistic regression analysis, we investigated the association between these indices and frailty as defined by the modified Cardiovascular Health Study (mCHS) criteria and the Kihon Checklist (KCL).

The fT3/fT4 was lower and the TFQI was higher in patients with mCHS-defined frailty than in those without frailty (p < .001 and p = .021, respectively). Patients with KCL-defined frailty had lower fT3/fT4 (p < .001) but not TFQI. The fT3/fT4 ratio correlated with age, cognitive function, depressive mood, nutritional status, and physical activity, whereas the TFQI was not. Using multivariate analysis, after adjustment for cognitive function, nutritional status, physical activity, and inflammatory markers, the fT3/fT4 and TFQI were independently associated with mCHS-defined frailty (odds ratio [OR] = 0.56 (per 0.1unit increase); 95% confidence interval [CI], 0.34–0.92 and OR = 2.68; 95%CI, 1.07–6.70, respectively). Using the receiver operating characteristic curve analysis, fT3/fT4 showed a modest, but relatively high area under the curve compared with TFQI, fT4, fT3, or thyroid-stimulating hormone, indicating a better discriminative ability.

Indices of impaired peripheral and central sensitivity to thyroid hormones were independently associated with phenotype frailty based on the cardiovascular health study.

The online version contains supplementary material available at 10.1186/s12877-025-06608-y.