Should the levothyroxine starting dose be tailored to disease severity in neonates with congenital hypothyroidism?

Early levothyroxine treatment is crucial to minimize neurocognitive impairment associated with congenital hypothyroidism. In this Practice Point commentary, I discuss the findings, implications, and limitations of the study of Mathai et al. in which neonates with congenital hypothyroidism were treated with variable initial doses of levothyroxine. A high initial levothyroxine dose was used for newborn babies with athyreosis, an intermediate dose for those with ectopic glands, and a low dose for those with dyshormonogenesis. Serum free T(4) levels normalized within 2 weeks, but serum TSH levels within up to 4 weeks. A dose adjustment (mostly a dose reduction) was required in about half of the neonates in the first 2 weeks of life. As Mathai et al. carried out no neuropsychological tests, we do not know if their approach has a more beneficial effect on neurocognitive outcomes than other treatment strategies. Nevertheless, as tailoring the levothyroxine dose to severity rapidly normalized serum free T(4) levels, one would predict a beneficial effect of this approach on neurocognitive outcome.