SAT-664 - Determinants of Central Thyroid Hormone Resistance in Children with Overweight/Obesity

Objectives
Obesity is viewed as a reversible form of central thyroid hormone resistance. This study aims to examine whether central thyroid hormone resistance is linked to other reversible obesity-related conditions—including low-grade inflammation, insulin resistance, liver steatosis, and hyperuricemia—in children and adolescents with overweight or obesity.

Methods
A total of 267 children and adolescents (144 males) with a BMI SDS > 1.3 were studied. Fasting serum concentrations of TSH, FT4, hs-CRP, ALT, uric acid, glucose, and insulin were measured. Body composition was assessed using bioelectrical impedance analysis, and fat distribution was evaluated by anthropometric measurements. Central thyroid hormone resistance was estimated using the TSH index (TSHI = log TSH + 0.1345 × FT4), and insulin resistance was assessed by the homeostasis model assessment (HOMA-IR = fasting plasma glucose × fasting plasma insulin/22.5). Group differences were analyzed using the Mann–Whitney U test, and associations were examined using Spearman rank correlation analysis.

Results
Median (Q1; Q3) age of participants was 10.5 (8.8; 12.8) years, with BMI SDS at 2.3 (2.0; 2.7), waist circumference (WC) SDS at 2.2 (1.9; 2.5), and body fat percentage at 36 (32; 40) %. Median levels were as follows: TSH: 2.500 (2.030; 3.260) mU/L, FT4: 15.5 (14.3; 16.8) pmol/L, TSH index: 2.98 (2.72; 3.34), hS-CRP: 1.8 (1.0; 3.4) mg/L, HOMA-IR: 3.48 (2.56; 5.95), ALT: 25 (19–34) IU/L, and uric acid: 4.9 (4.1; 5.7) mg/L. Males demonstrated significantly higher median FT4 (15.8 vs. 15.3 pmol/L; p = 0.042), ALT (26 vs. 24 IU/L; p = 0.018), uric acid (5.0 vs. 4.8 mg/L; p = 0.010), fasting glucose (89 vs. 87 mg/dL; p < 0.001), and WC SDS (2.25 vs. 2.13; p = 0.014), but a similar TSH index. 120 (43 %) subjects had a TSH index above the median reference value, while 5 had a value above the reference range. TSH indices were negatively correlated with age (r = -0.135; p = 0.027) and positively with BMI SDS (r = 0.116; p = 0.057), body fat percentage (r = 0.197; p = 0.002), WC SDS (r = 0.167; p = 0.008), TSH (r = 0.793; p < 0.001), and FT4 (r = 0.352; p < 0.001). No significant correlation was found between TSH index and serum ALT, uric acid, glucose, insulin, or HOMA-IR.

Conclusion
Central thyroid hormone sensitivity correlates with adiposity and central fat distribution, but not with low-grade inflammation, insulin resistance, elevated transaminases, or hyperuricemia.

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