The significance of relatively low thyroxine (T4) levels in preterm infants with and without respiratory distress syndrome (RDS) was assessed by evaluating the free T4 level, the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH), and intellectual development in infants ≤35 weeks with cord blood T4 concentrations sjlt 6.5 μg/100 ml. Fifty-four (19 well, 28 with RDS, and seven without RDS and sick) of 215 premature infants (25%) and 27 of 8,831 term infants (0.3%) had cord T4 levels sjlt 6.5 μg/100 ml. Serum T4 levels were measured in 39 surviving preterm infants (20 RDS and 19 well) during the first 5 days of life and at 2, 4, 24, and 52 weeks postnatally. Serum total T4 level during the first week was 4.5 ± 0.3 μg/100 ml (mean ± SEM). Free T4 levels ranged from 1.1 to 2.2 ng/100 ml (normal adult range 0.8 to 2.3 ng/100 ml). Administration of TRH resulted in a clear increase in both TSH and T4 levels in all infants. T4 levels increased significantly ( r = .70, P sjlt .01) with increasing postnatal age, reaching stable levels by 6 to 7 weeks. Developmental quotients obtained in the infants with low T4 levels were no different from those found in a matched control population at 12 months of age. The low T4, free T4, and TSH concentrations and normal TSH responses to TRH found in these infants are characteristic of hypothalamic (tertiary) hypothyroidism, but differ from classic tertiary hypothyroidism in that the disorder was transient. The normal intellectual development at 12 months of age and the spontaneous increase in T4 levels that occurs over the first six weeks of life suggest that the low T4 levels in these infants reflect a benign relative delay in maturation of hypothalamic-pituitary-thyroid control.
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