{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:05:06Z","timestamp":1789621506244,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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\u20139.0 years) with height SDS &amp;lt; \u20131.0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A significant linear positive association was found (P-overall &amp;lt; 0.001; P-nonlinear = 0.0719). FT3\/FT4 and FT3 showed significant partial mediation, accounting for 9.12% (P &amp;lt; 0.001) and 11.60% (P\u00a0=\u00a00.0108) 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 &amp;lt; \u20132.0). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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 \u201cthrifty\u201d regulatory strategy and offering a potential target for nutritional intervention. These mediation findings reflect statistical associations and require prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1941425","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:49:42Z","timestamp":1789620582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Child Health Care; Clinical Research Center of Child Health Care and Developmental & Behavioral Disorders, Institute of Maternal and Child Health, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College, Huazhong University of 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