Sexual dimorphism of thyroid function in newborns with congenital hypothyroidism.

Several characteristics of congenital hypothyroidism (CH) from thyroid dysgenesis (ectopy and athyreosis) are sexually dimorphic: girls are more often affected, and boys are twice more likely than girls to have absent knee epiphysis at diagnosis, an indicator of severity of CH. Whether the biochemical severity of CH is sexually dimorphic is unknown. We therefore reviewed the charts of all newborns referred to our clinic from 1990 to 2004 because of a TSH greater than 15 mU/liter on newborn screening. In ectopy (24 boys, 78 girls) at screening, median TSH was lower in boys than girls (75 vs. 135 mU/liter, P = 0.017), whereas total T4 was higher (123 vs. 68 mmol/liter, P = 0.003); the same differences were present at diagnosis: TSH was 90 and 284 mU/liter (P = 0.001) and free T4 10 and 7 pmol/liter (P = 0.049) in boys and girls, respectively. The log-linear relationships between TSH and T4 at screening and diagnosis were similar in both sexes. In athyreosis (10 boys, 14 girls) at screening and diagnosis, TSH was higher in boys [308 vs. 207 (P = 0.053) and 712 vs. 555 mU/liter (P = 0.0057)]. In infants with an orthotopic gland (dyshormonogenesis, nine boys, 13 girls), there was no sex difference in biochemical severity of CH. In conclusion, sexual dimorphism in biochemical severity of CH from thyroid dysgenesis is apparent but differs according to etiology. These novel findings suggest that sexual dimorphism should be considered as a modulator of the mechanisms underlying the fate and function of ectopic thyroid cells.