Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment.

Abstract

We have previously reported that despite neonatal screening, children with severe congenital hypothyroidism treated at 5 weeks of age with 6 micrograms/kg.day levothyroxine have clinically significant intellectual impairment, whereas those with the moderate form of the disease are indistinguishable from controls. The developmental outcome of children with severe congenital hypothyroidism treated earlier with higher initial doses of levothyroxine remained to be determined. In the present study, 45 infants with permanent congenital hypothyroidism detected by neonatal screening are described. For the group, the median age at starting treatment was 14 days, and the median initial dose of levothyroxine was 11.6 micrograms/kg.day. Based on the area of their knee epiphyses at diagnosis, the patients were divided into 2 subgroups: severe (< 0.05 cm2; n = 10) and moderate (> or = 0.05 cm2; n = 35). The psychomotor development of 8 patients in each subgroup, matched for the socioeducational level of their families, was assessed at 18 months. Mean plasma free T4 levels were supraphysiological during the first few months of life, but mean plasma T3 levels remained within the normal range, and there were no signs or symptoms of hyperthyroidism. The mean plasma TSH concentration was less than 4.5 mIU/L 4 weeks after starting treatment. Bone maturation remained delayed at 12 months in the severe cases and was not unduly advanced in the moderate cases. The mean (+/- SD) developmental quotients at 18 months were similar in severe and moderate cases (107 +/- 10 and 110 +/- 5, respectively). We conclude that with earlier treatment and a higher initial dose of levothyroxine, the early developmental outcome of infants with severe congenital hypothyroidism is now indistinguishable from that of infants with the moderate form of the disease who were used as controls.

In congenital hypothyroidism bone maturation at birth may be a predictive factor of psychomotor development during the first Year of life irrespective of other variables related to treatment

“…In some studies CH severity has been found to be significantly associated with neurocognitive outcome, probably as a consequence of the deleterious effects of prenatal thyroid failure on central nervous system maturation (4, 27). However, this negative impact of severe versus mild CH on DQ can be counteracted by an early and high dose L-T 4 treatment (19,28). On the other hand, children with mild CH who are usually prone to a normal psychomotor development, may also experience an insufficient long term evolution if treated late with a low initial L-T 4 dose (21).…”

Programa de triagem neonatal para hipotireoidismo congênito no nordeste do Brasil: critérios diagnósticos e resultados

“…A introdução dos programas de triagem neonatal representa importante instrumento de prevenção de retardo mental com adequada e tempestiva terapia substitutiva com L-tiroxina para os casos de HC, propiciando o desenvolvimento neuropsíquico da criança e de critérios para sua classificação (4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) Utilizamos os seguintes procedimentos: quantificou-se o número de crianças triadas na capital e no interior e calculou-se a média aritmética, mediana, o percentual e o desvio-padrão das idades das crianças triadas e das concentrações do TSH coletados em papel-filtro (tipo SS 903). O sangue foi colhido com lanceta do calcanhar das crianças, após o nascimento, e o TSH neonatal (TSHneo) foi dosado pelo método imunofluorimétrico da PerkinElmer Life and Analytical Sciences, Wallac, Turku, Finland.…”

Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil

“…A regionalização do Programa de Triagem Neonatal proporcionada pela implantação do Laboratório de Triagem Neonatal no HCFMRP permitiu que o início do tratamento das crianças afetadas para hipotireodismo congênito diminuísse de 70,7 ± 40,7 dias de vida para 25,9 ± 14,2 dias, ocorrendo em grande parte das vezes dentro do tempo considerado ideal, ou seja, até a 2ª semana de vida 9,10,24,25,26,27 . Na avaliação realizada em Santa Catarina, em 1998, o percentual de crianças atendidas até 28 dias de vida ainda foi de 46,7% 19 17 .…”