Individualized treatment to optimize eventual cognitive outcome in congenital hypothyroidism

In congenital hypothyroidism (CH), age-specific reference ranges (asRR) for fT₄ and thyrotropine (TSH) are usually used to signal over/under-treatment. We compared the consequences of individual fT₄ steady-state concentrations (SSC's) and asRR regarding over-treatment signaling and intelligence quotient at 11 y (IQ₁₁) and the effect of early over-treatment with high L-T₄ dosages on IQ₁₁.

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 fT₄SSC's or asRR. Three groups were formed, based on severity of over/under-treatment 0-5 mo (severe, mild, and no over/under-treatment).

FT₄ and TSH asRR missed 41-50% of the over-treatment episodes and consequently 22% of the over-treated patients, classified as such by fT₄SSC's. Severe over-treatment 0-5 mo led to lowered IQ₁₁'s and to a 5.5-fold higher risk of IQ₁₁ < 85 than other treatment regimes. Under-treatment had no effect on development scores. Initial L-T₄ dosages >10 µg/kg resulted in a 3.7-fold higher risk of over-treatment than lower dosages.

Data suggest that asRR, compared to fT₄SSC's, signal over-treatment insufficiently. Using fT₄SSC's and avoiding over-treatment may optimize cognitive outcome. Lowered IQ₁₁'s are usually a late complication of severe early over-treatment.