Free thyroid hormones in evaluating persistently elevated thyrotropin levels in children with congenital hypothyroidism on replacement therapy.

Some children with congenital hypothyroidism receiving L-T4 therapy have elevated serum TSH levels despite having normal serum T4 concentrations, suggesting that they have a higher threshold for the feedback regulation of TSH release. To further study this possibility, we determined serum free T4 (FT4) and T3 (FT3) concentrations in two groups of L-T4-treated hypothyroid children. Group A consisted of 10 patients with high serum TSH levels; group B consisted of 10 patients with normal TSH levels. All patients were clinically euthyroid, and serum total T4 and T3 concentrations were similar in the two groups. A third (control) group (C) consisted of randomly selected normal children. The three groups were age matched. Serum FT3 and FT4 were significantly lower in group A compared to group B. Serum FT4 and T4 were higher and TSH was lower in group B compared to group C. The T4/T3 ratio wash higher in both groups of children with hypothyroidism than in group C. We conclude that in most patients a high serum TSH was due to inadequate L-T4 therapy, as shown by free hormone concentrations (low) but not by total hormone levels (normal). This suggests that L-T4 therapy should be monitored by measurement of TSH and free hormone concentrations. The latter also can be used to indicate moderate overdosage, not clinically detectable, as shown by the comparison between groups B and C. Measurement of serum total T4, as indicated by the lack of difference between groups A and B and also by T4/T3 ratio, cannot be considered a reliable index of therapeutic adequacy in such children.