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

L. Chiovato, L. Giusti, M. Tonacchera, M. Ciampi, C. Mammoli, F. Lippi, P. Lapi, S. Bargagna, P. Dini, G. Ferretti, M. Marcheschi, G. Cesaretti, G. Saggese, G. F. Fenzi, P. Pfanner, A. Pinchera

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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.

Original languageEnglish
Pages (from-to)957-964
Number of pages8
JournalJournal of Endocrinological Investigation
Issue number11
Publication statusPublished - 1991


  • Congenital hypothyroidism
  • free thyroid hormones
  • growth in height and weight
  • L-thyroxine therapy
  • neonatal thyroid screening
  • neuropsychological development
  • TSH

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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