OUTCOME OF SEVERE CONGENITAL HYPOTHYROIDISM - CLOSING THE DEVELOPMENTAL GAP WITH EARLY HIGH DOSE LEVOTHYROXINE TREATMENT

We have previously reported that despite neonatal screening, children with severe congenital hypothyroidism treated at 5 weeks of age with 6 mu g/kg . day levothyroxine have clinically significant intellectual impairment, whereas those with the moderate form of the disease are in distinguishable from controls. The developmental outcome of children w ith severe congenital hypothyroidism treated earlier with higher initi al doses of levothyroxine remained to be determined. In the present st udy, 45 infants with permanent congenital hypothyroidism detected by n eonatal screening are described. For the group, the median age at star ting treatment was 14 days, and the median initial dose of levothyroxi ne was 11.6 mu g/kg . day. Based on the area of their knee epiphyses a t diagnosis, the patients were divided into 2 subgroups: severe (< 0.0 5 cm(2); n = 10) and moderate (greater than or equal to 0.05 cm(2): n = 35). The psychomotor development of 8 patients in each subgroup, mat ched for the socioeducational level of their families, was assessed at 18 months. Mean plasma free T-4 levels were supraphysiological during the first few months of life, but mean plasma T-3 levels remained wit hin the normal range, and there were no signs or symptoms of hyperthyr oidism. The mean plasma TSH concentration was less than 4.5 mIU/L 4 we eks after starting treatment. Bone maturation remained delayed at 12 m onths in the severe cases and was not unduly advanced in the moderate cases. The mean (+/- SD) developmental quotients at 18 months were sim ilar in severe and moderate cases (107 +/- 10 and 110 +/- 5, respectiv ely). We conclude that with earlier treatment and a higher initial dos e of levothyroxine, the early developmental outcome of infants with se vere congenital hypothyroidism is now indistinguishable from that of i nfants with the moderate form of the disease who were used as controls .