Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism.
OBJECTIVE
To test whether early treatment with a high initial dose of levothyroxine can prevent suboptimal mental development in all neonates with congenital hypothyroidism (CH).


METHODS
Sixty-one patients, 27 with severe CH and 34 with mild CH, were treated either early (<13 days) or late (> or =13 days) with either a high initial dose of levothyroxine (> or =9.5 microg/kg/d) or a low initial dose (<9.5 microg/kg/d). With these criteria, 4 treatment groups were formed. The results of the Bayley test, performed at the age of 10 to 30 months and expressed as mental developmental index (MDI) and psychomotor developmental index (PDI), were related to socioeconomic status, treatment group, initial free thyroxine (FT(4)) concentration, and mean FT(4) concentration during the first 3 months of treatment (FT(4)-A) and the ensuing 9 months (FT(4)-B).


RESULTS
Mean (+/- SD) MDI was 113 +/- 14, and mean PDI was 114 +/- 12. In the severe CH group, only the patients treated early with a high initial dose had normal MDI scores (124 +/- 16), whereas the scores of the other groups ranged from 97 to 103. In contrast, all patients in the mild CH group had normal scores (range, 122-125), except those in the group treated late with a low initial dose, whose score was 110 +/- 10. Forty-three percent of the variance in MDI and PDI scores was explained by treatment factors, such as the treatment group, initial FT(4) concentration, FT(4)-A, and FT(4)-B.


CONCLUSIONS
Our data suggest that optimal treatment includes achievement of euthyroidism before the third week of life by initiation of therapy before 13 days with a levothyroxine dose above 9.5 microg/kg/d and maintenance of FT(4) concentrations in the upper normal range during the first year. Thus treated, patients with CH can achieve normal psychomotor development at 10 to 30 months, irrespective of the severity of the disease.
Bongers-Schokking
J J
JJ
Department of Endocrinology, the Department of Child and Adolescent Psychiatry, the Academic Hospital Sophia Children's Hospital, Rotterdam, The Netherlands.
Koot
H M
HM
Wiersma
D
D
Verkerk
P H
PH
de Muinck Keizer-Schrama
S M
SM
D002657:Child Development; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000151:congenital* / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000187:drug effects*; D013974:Thyroxine / Q000008:administration & dosage*; D013997:Time Factors
D013974:Thyroxine