Frontiers in Endocrinology · Nov 2, 2026
Thyroid Hormone Sensitivity and Cardiovascular Disease in the Euthyroid Population: Indices, Mechanisms, and Translational Gaps
By Guojie Ye, Yingyue Zhang, Yunhe Bai et al.
Thyroid hormones regulate cardiac contractility, electrophysiology, vascular tone, and lipid metabolism. Beyond overt thyroid disease, altered tissue sensitivity to thyroid hormone can be quantified in people with normal circulating hormone levels using central indices (TFQI, PTFQI, TSHI, TT4RI) derived from free thyroxine and TSH, and a peripheral index (the FT3/FT4 ratio). This review summarizes what these indices can and cannot tell us about cardiovascular risk. Most of the evidence is cross-sectional and comes from a small number of cohorts. Reduced sensitivity tracks most consistently with atherogenic dyslipidemia, whereas associations with arrhythmia, atherosclerosis, hypertension, and heart failure vary in direction and strength. The central indices, however, largely capture variation in the hypothalamic-pituitary-thyroid set point rather than tissue sensitivity, and none has been validated against a physiological reference standard. Single measurements add further uncertainty through substantial within-person variation. Two translational problems remain: the risk markers and the available TRβ-selective drugs act on different physiological axes, and almost no study has tested whether adding an index improves established risk models. Before these indices can inform clinical decisions, their repeatability and construct validity must be established, causality tested in prospective and genetic designs, and incremental predictive value demonstrated.