ArticleFrontiers in endocrinology2026
Mediating role of peripheral thyroid hormone conversion efficiency in the association between BMI and IGF-1 in children with growth retardation: a cross-sectional 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
Objective: To examine the association between body mass index (BMI) standard deviation score (SDS) and insulin-like growth factor-1 (IGF-1) SDS and whether thyroid hormones mediate it, focusing on the peripheral conversion marker free triiodothyronine/free thyroxine (FT3/FT4) ratio, in prepubertal children (2.0-9.0 years) with height SDS < -1.0. Methods: This retrospective cross-sectional study included 1,242 such children. Restricted cubic splines assessed the BMI-IGF-1 relationship, and Bootstrap mediation (5,000 resamples) tested indirect effects of FT3/FT4, FT3, FT4, and thyroid-stimulating hormone (TSH), adjusted for sex, age and height SDS. Reverse mediation, subgroup, interaction, Monte Carlo power, and E-value sensitivity analyses were also performed. Results: A significant linear positive association was found (P-overall < 0.001; P-nonlinear = 0.0719). FT3/FT4 and FT3 showed significant partial mediation, accounting for 9.12% (P < 0.001) and 11.60% (P = 0.0108) of the total effect, respectively; TSH and FT4 did not. Sensitivity analyses confirmed robustness after stricter prepubertal cutoffs and exclusion of overweight/obese children. Notably, only FT3/FT4 remained significant after excluding suspected Growth Hormone Deficiency (GHD) (IGF-1 SDS < -2.0). The FT3/FT4 ratio remained a significant mediator across all subgroup analyses. Reverse mediation analysis yielded a substantially smaller indirect effect in the reverse direction. E-values for FT3/FT4 and FT3 were 1.0764 and 1.0609, respectively. Conclusion: In this growth-retarded prepubertal cohort, BMI and IGF-1 are linearly associated. The FT3/FT4 ratio is statistically supported as a partial mediator with moderate effect size but strong statistical robustness, while the central TSH pathway is uninvolved, supporting a peripheral "thrifty" regulatory strategy and offering a potential target for nutritional intervention. These mediation findings reflect statistical associations and require prospective validation.
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