Sensitivity to thyroid hormones and cardiometabolic risk in euthyroid obese children: a cross-sectional study

Background: The typical biochemical phenotype related to obesity, that is high serum thyrotropin (TSH) within normal range, low/normal free thyroxine (FT4) and increased free triiodothyronine (FT3) levels, can be interpreted as a resistance to thyroid hormones. It is unclear the role played by thyroid hormones in the pathogenesis of metabolic derangement associated with obesity. Aim: To investigate the association between thyroid hormones sensitivity and cardio-metabolic risk factors in a cohort of euthyroid obese youths. Material and Methods: This is a single-center, cross-sectional, observational study on children with euthyroid obesity. Each patient underwent clinical and auxological examination and laboratory workup including an Oral Glucose Tolerance Test (OGTT) and the measurement of serum TSH, FT4, FT3 and lipid profile. We measured the parameters representing central and peripheral sensitivities to thyroid hormones (Thyroid Feedback Quantilebased Index (TFQI), TSH Index (TSHI), Thyrotroph Thyroxine Resistance Index (TT4RI), Parametric Thyroid Feedback Quantilebased Index (PTFQI) and FT3/FT4 ratio, respectively), and we compared them in different subgroups of patients according to the TSH level, the presence/absence of insulin resistance and the severity of obesity; finally, we evaluated the association with some cardiometabolic risk factors. Results: Four hundred ninety-one Caucasian euthyroid obese children and adolescents (age 9.93±2.90) were recruited. Two hundred twenty-five subjects (45.8%) had a high-normal TSH level (TSH 2.3-5.0 mU/L), 315 subjects (64.2%) were severe obese (BMI standard deviation (SD) > 2.5 according to the WHO reference). Two hundred sixty-one subjects (53.1%) had insulin resistance defined by HOMA-IR > 2.5 in prepubertal children and > 4 in pubertal ones. Severe obese children as well as subjects with highnormal TSH had higher FT3/FT4 ratio values comparing with those with BMI < 2.5 SD and with low-normal TSH values, respectively. There were no differences in indices of thyroid hormones sensitivity between children with insulin resistance and those normoinsulinemic. On regression analysis, BMI-SD was positively associated with FT3/FT4 ratio values (B= 2.202, p<0.001); area under the glucose curve and area under the insulin curve were positively associated with TT4RI (B= 1.110, p=0.034; B= 7.670, p=0.001 respectively); HDL values was negatively associated with TSHI values (B= -9.140, p=0.005). Conclusions: Higher values in resistance to thyroid hormones indices are associated with an unfavorable metabolic phenotype related to obesity. These evidences could suggest the potential role of sensitivity to thyroid hormones in the development of metabolic diseases.