Dynamics of the plasma concentrations of TSH, FT4 and T3 following thyroxine supplementation in congenital hypothyroidism.

Objective: The dynamics of the plasma concentrations of various diagnostic determinants of thyroid function were analysed in children with congenital hypothyroidism (CH) after the start of T4 supplementation. The description of the biochemical dynamics of TSH and free T4 (FT4) during the first period of thyroxine treatment is important to depict the practical outlines of the initial dosage of T4 and dosage adjustments for newborns with variable forms of CH.

Design: A retrospective analysis was performed of frequent plasma TSH, total T4 (T4), FT4 and total T3 (T3) measurements in 30 CH neonates during the first weeks of treatment, treated with initial daily T4 dosages ranging from 4.8 to 11.1 microg/kg.

Results: A 50% reduction in the initial plasma TSH concentration was achieved after 3-4 days of treatment, independent of CH severity. At a median of 32 days after the start of T4 supplementation, plasma TSH ranged between 0.4 and 4.0 mU/l. The mean interval needed for FT4 to reach the age-related normal values (12-29 pmol/l) was 3 days. The increase in plasma T3 concentrations levelled off within a few days, when T4 reached concentrations of around 100 nmol/l.

Conclusions: Plasma T3 and FT4 concentrations reach the normal range a few days after thyroxine treatment is started. By contrast, normalization of plasma TSH concentration takes several weeks. At the time that plasma TSH is normalized, CH neonates show a higher range of plasma FT4 concentrations than the normal range. When TSH normalization is the goal of treatment in CH, the target range for plasma FT4 during treatment in the first months needs to be adapted. During the first month of treatment the plasma TSH concentration is not helpful in assessing the proper T4 supplementation dosage. Once plasma TSH has reached normal values, it becomes a reliable determinant in addition to plasma FT4.