The association between serum Thyrotropin within the reference range and cardiometabolic risk in obese children

Background: The adaptative increase of serum thyrotropin (TSH) levels in obese subjects may affect the metabolic regulation of body tissues and thus promote an unfavorable cardiometabolic profile. Aim: To investigate the association between serum TSH, free thyroxine (FT4) and cardiometabolic risk factors in euthyroid obese children and adolescents. Material and Methods: Four hundred ninety-one Caucasian euthyroid obese children and adolescents (age 9.93±2.90) were recruited. Subjects with genetic and/or endocrine causes of obesity, diabetes, chronic diseases, chronic pharmacological therapies and overt or subclinical hypo-/hyperthyroidism, arterial hypertension were excluded. Each patient underwent clinical and auxological examination and laboratory workup including an OGTT and the measurement of serum TSH, FT4 and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) and for β-cell function (HOMA-B), triglyceride to high density lipoprotein cholesterol (TG/HDL-c) ratio, total cholesterol to HDL-c (Tc/HDL-c) ratio, atherogenic index of plasma (AIP), insulinogenic index, area under the glucose curve (AUCglu) and area under the insulin curve (AUCins) were calculated. Results: The mean TSH level in our cohort was 2.31 (range 0.48-5) mU/L with a mean FT4 level of 16.62 (range 12-22) pmol/L. Two hundred twenty-five subjects (45.8%) had a high-normal TSH level (TSH 2.3-5.0 mU/L), among whom 151 subjects (67.1%) were severe obese (BMI standard deviation (SD) ≥ 2.5 according to the WHO reference). Increasing concentrations of TSH were associated with increasing values of BMI SD (B =0.067, p=0.012), Tc level (B =2.860, p=0.040) , LDL-C level  (B= 3.017, p=0.022) , Tc/HDL-c ratio  (B =0.080, p=0.046), HOMA-IR (B =0.376, p=0.009), AUCgluc (B =4.636, p=0.021) and AUCins (B =19.501, p=0.022) after adjustment for some confounding variables (age, sex, pubertal stage, HOMA-IR, BMI-SD). In addition TSH level was positively correlated with BMI-SD (rs=0.113; p=0.012), Tc (rs =0.121; p=0.008), LDL-c (rs =0.104; p=0.031), TG/HDL-c (rs =0.104; p=0.033) , Tc/HDL-c (rs =0.134; p=0.005) fasting plasma insulin (rs =0.114; p=0.012), HOMA-IR (rs =0.123; p=0.007), HOMA-B (rs =0.133; p=0.004), AUCglu (rs =0.178; p=0.005), AUCins (rs =0.122; p=0.045), AIP (rs =0.100; p=0.040). However, no association was found between serum TSH and dyslipidemia, impaired glucose metabolism and severe obesity. None of the analyzed cardiometabolic risk factors were predictive of a high-normal TSH level. Serum FT4 was negatively associated with BMI-DS (B= -0.044, p=0.000) and negative correlated with fasting plasma glucose (rs =-0.110; p=0.016). Conclusions: Even in euthyroid obese children and adolescents increasing TSH is associated with an increasing cardiometabolic risk.