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In congenital hypothyroidism (CH), age-specific reference ranges (asRR) for fT
and thyrotropine (TSH) are usually used to signal over/under-treatment. We compared the consequences of individual fT
steady-state concentrations (SSC's) and asRR regarding over-treatment signaling and intelligence quotient at 11 y (IQ
) and the effect of early over-treatment with high L-T
dosages on IQ
.
Sixty-one patients (27 severe, 34 mild CH) were psychologically tested at 1.8, 6, and 11 y. Development scores were related to over-treatment in the period 0-24 mo, relative to either individual fT
SSC's or asRR. Three groups were formed, based on severity of over/under-treatment 0-5 mo (severe, mild, and no over/under-treatment).
FT
and TSH asRR missed 41-50% of the over-treatment episodes and consequently 22% of the over-treated patients, classified as such by fT
SSC's. Severe over-treatment 0-5 mo led to lowered IQ
's and to a 5.5-fold higher risk of IQ
< 85 than other treatment regimes. Under-treatment had no effect on development scores. Initial L-T
dosages >10 µg/kg resulted in a 3.7-fold higher risk of over-treatment than lower dosages.
Data suggest that asRR, compared to fT
SSC's, signal over-treatment insufficiently. Using fT
SSC's and avoiding over-treatment may optimize cognitive outcome. Lowered IQ
's are usually a late complication of severe early over-treatment.