Central and peripheral sensitivity to thyroid hormones and glucose metabolism in prepubertal children with obesity: pilot multicenter evaluation.

Purpose: An alteration of central and peripheral sensitivity to thyroid hormones (THs) seems to be associated with an increased risk of prediabetes in adulthood. Aims of this study was to evaluate the relationship between the sensitivity to THs, the severity of overweight and the glyco-metabolic alterations in prepubertal euthyroid children with obesity.

Methods: Prepubertal subjects with simple obesity and matched controls were recruited from three Italian pediatric endocrinology centers and underwent clinical and biochemical evaluations. HOMA-IR, HOMA-β, insulinogenic index, Matsuda index were evaluated in children with obesity. Indexes of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; Thyroid Feedback Quantile-based Index, TFQI; Parametric TFQI, PTFQI) to thyroid hormones were calculated in both groups.

Results: Eighty prepubertal children with obesity (Group 1; mean age 7.60 ± 1.51 years) and 28 healthy normal-weight controls (Group 2) were recruited. BMI and leptin were higher in group 1 than in group 2. The FT3/FT4 ratio correlated negatively with HOMA-β (r = -0.29; p = 0.01) and was significantly positively associated with BMI (p = 0.03), IR (p = 0.03) and fasting blood glucose (p = 0.04) in group 1. TT4RI, TSHI, PTFQI, TFQI, were significantly negatively associated with Matsuda-index, IGI and BMI in group 1.

Conclusion: Central and peripheral sensitivity to thyroid hormones is significantly affected by the severity of overweight and the presence of IR. Altered tissue sensitivity to THs in the prepubertal children with obesity could be implicated in the pathogenesis of glucose metabolism impairment.