How Should We Be Treating Children with Congenital Hypothyroidism?

Abstract

Early detection by newborn screening and appropriate L-thyroxine treatment leads to normal or near-normal neurocognitive outcome in infants with congenital hypothyroidism. Many newborns with congenital hypothyroidism have some residual thyroid hormone production, and even in those with athyreosis, transplacental passage of maternal thyroid hormone offers some protection for a time. Given the serum T4 half-life of 6 days, the neonatal T4 level will fall and disappear over the first 2-3 weeks of life. Thus, there is a crucial 'window of opportunity' to correct the hypothyroidism and minimize the time the brain is exposed to hypothyroxinemia. While there are few truly prospective, randomized clinical trials investigating treatment parameters, studies measuring IQ outcome support a starting L-thyroxine dose of 10-15 microg/kg/day. Further, studies show that the most severely hypothyroid infants are at risk for a 5-20 point decrease in IQ. Such infants may benefit from a starting dose of 12-17 microg/kg/d, which has been shown to normalize T4 in 3 days and TSH in 2 weeks. Target serum T4 or free T4 levels appear to be higher in the first two weeks of treatment. Infants require more frequent laboratory monitoring, every 1-2 months in the first 6 months and every 3-4 months until age 3 years, as the developing brain has a critical dependence on thyroid hormone in the first 2-3 years of life.

Risk factors for neurodevelopmental deficits in congenital hypothyroidism after early substitution treatment

“…In a review of ten studies that examined the effects of different starting L-T 4 doses on psychometric outcome, two reported no effect, six reported a higher IQ with higher starting doses, and another two reported a higher IQ with lower starting doses [22]. Furthermore, an additional study did not find a correlation between the initial L-T 4 dose and outcome [25].…”

Thyroid hormones and fetal neurological development

“…If thyroid hormone replacement for congenital hypothyroid babies is not initiated soon after birth, further impairment of cognitive development occurs. More recent evidence suggests that even mild reductions in maternal thyroid hormone levels in early pregnancy are associated with reduced IQ in offspring (LaFranchi & Austin 2007, Gyamfi et al 2009). The molecular mechanisms by which thyroid hormones affect fetal neurological structures are still not well understood.…”

Tamizaje nacional unificado de hipotiroidismo congénito en el Perú: un programa inexistente

“…La razón primordial de la necesidad de tratamiento inmediato en casos confirmados de HC se debe a que en las etapas tempranas del desarrollo (los primeros 3 años de vida) el cerebro tiene dependencia crítica de la hormona tiroidea (1) . La demora en el tratamiento del HC puede ocasionar el deterioro de la función cerebral, así como pérdida del coeficiente intelectual y/o alteración del desarrollo psicomotor normal (14) .…”

“…La prevalencia mundial de HC es reportada como 1: 4000 nacidos vivos en países desarrollados del hemisferio norte (1) . A nivel latinoamericano, un estudio de prevalencia de HC en Argentina durante los años 1997-2010 describió 1:2367 -1:3108 nacidos vivos (2) .…”