Evaluation of L-thyroxine replacement therapy in children with congenital hypothyroidism

Abstract

The outcome of L-thyroxine (L-T₄) replacement therapy in children with congenital hypothyroidism (CH) remains to be completely evaluated. In this paper the overall pattern of response to L-T₄ replacement therapy was studied in a group of 19 children with CH diagnosed by neonatal screening (10 with hypoplastic/aplastic thyroid disease, group H/A; 9 with gland ectopy, group E) who were followed-up for 60 ± 27 months (mean ± SD). With 1 exception serum T₄ at diagnosis was > 2 µg/dl in children of group E and < 2 µg/dl in those of group H/A. The initial dose of L-T₄ (8–10 µg/kg BW/day) was modified in relation to age and weight in order to maintain serum TSH ≼ 5 µU/ml and FT₃ in the normal range. A general inverse correlation between serum TSH and FT₄ or FT₃ concentrations was found, and the mean levels of serum FT₄ and FT₃ were significantly higher according to the following order of TSH results: low TSH (0–0.5 µU/ml) > normal (>0.5–5 µU/ml) > elevated TSH (>5 µU/ml). TSH levels < 5 µU/ml were associated with FT₄ values in the upper half of the normal range (54% of observations) or even higher (46%). Elevation of serum FT₄ alone with FT₃ values in the normal range did not result in clinical thyrotoxicosis, alteration of growth or premature craniosynostosis. Mean L-T₄ doses (µg/kg BW/day) administered to CH children were: 7.0 ± 1.6 between 1 and 6 months; 5.2 ± 0.9 between 6 and 12 months; 4.0 ± 0.6 between 1 e 5 yr; 3.4 ± 0.6 over 6 yr. In general, the mean L-T₄ closes given to children showing low, normal or elevated TSH were widely overlaped. Growth in weight and height was normal, no significant difference being observed in children of group H/A vs. those of group E. Mental development was within the normal range, but at age 12 months children in group H/A had significantly lower DQ scores than those in group E, and at age 3 yr both groups of CH children had significantly lower IQ scores than unaffected controls. In conclusion: i) in children with CH serum TSH can be suppressed to normal or even subnormal concentrations provided that enough L-T₄ is given to maintain FT₄ in the upper half of the normal range or slightly higher; ii) sporadic elevations of TSH during treatment could be attributed to: failure to reassess the dose of L-T₄ following the infant’s rapid gain in weight, lack of compliance, malabsorption of the drug, misunderstanding of prescription; iii) neuropsychological development was within the normal range of tests; however, the absence of functioning thyroid tissue, as shown by low T₄ at diagnosis and by negative radioisotope imaging, was a risk factor for lower mental scores.