A lower activity of the thyroid axis within the clinical reference range is related to a dysmetabolic phenotype in adult populations. We posited that such an association is already present as early as in prepubertal childhood. Serum
thyroid stimulating hormone (TSH) and free T4, body fat (bioelectric impedance),
insulin resistance (homeostasis model assessment of
insulin resistance (HOMA(IR))), total and high molecular weight (HMW)-
adiponectin and serum
lipids were assessed in 234 euthyroid prepubertal children (113 boys and 121 girls) attending primary care clinics. Visceral fat (abdominal ultrasound) was measured in a subset of these subjects (n = 147; 74 boys and 73 girls). Explants of visceral adipose tissue from an additional six prepubertal children (three boys and three girls) were used to study the regulation of total and HMW-
adiponectin by
thyroid hormone. Serum free T4 was in girls independently associated with HMW-
adiponectin, HOMA(IR) and visceral fat, so that circulating HMW-
adiponectin decreased by 30% (β = 0.305 P < 0.005, R(2) = 0.13) and HOMA(IR) and visceral fat increased, respectively, by 90% (β = -0.255 P < 0.01, R(2) = 0.05) and 30% (β = -0.369, P < 0.005, R(2) = 0.12) from the highest to the lowest tertile of serum free T4. Nonsignificant differences in these parameters were found in boys. Treatment of visceral fat explants with
thyroid hormone increased total and HMW-
adiponectin by 70% and 53%, respectively, above control values (P < 0.01). In conclusion, a dysmetabolic phenotype, consisting of relative
hypoadiponectinemia,
insulin resistance and increased visceral fat, is associated with low-normal serum free
thyroxine in euthyroid prepubertal girls. These associations may be partly explained by a positive regulation of HMW-
adiponectin secretion by
thyroid hormone.