Effects of Initial Levothyroxine Dose on Growth and Neurodevelopmental Outcomes During the First Year of Life in Children with Congenital Hypothyroidism

Background: An important issue in the management of congenital hypothyroidism (CH) is the best initial dose of levothyroxine (L-T4) in order to achieve optimal neurocognitive outcomes. Both European and American guidelines suggest an initial dose of 10–15 mg/kg per die but trials on long-term effects of different doses within this range are lacking. Objective and hypotheses: This was a multicenter randomized trial to evaluate the effects of the initial dose of L-T4 on growth and neurodevelopmental outcomes in children with CH. Method: Seventy-two children with CH diagnosed by neonatal screening were enrolled in the study. They were randomly assigned to receive an initial L-T4 dose of 10–12.5 mg/kg per die (group A) or 12.6– 15 mg/kg per die (group B). All patients underwent clinical examination and FT4 and TSH measurement after 7–10 days of treatment and at the age of 1.5, 3, 6, 9 and 12 months. At the age of 12 months they underwent Griffiths Mental Development Scales to evaluate cognitive development. Four patients were lost to the follow-up and two patients have not yet reached 12 months of age; therefore only 66 children (32 from group A and 34 from group B) concluded the first year of study. Results: No significant differences were detected in auxological parameters between the two groups. The intelligent quotient (IQ) at 12 months of age was similar in the two groups (104.79G13.18 vs 104.77G12.81). IQ correlated with age at diagnosis (rZK0.03, PZ0.02) and FT4 levels after 7–10 days of L-T4 therapy (rZ0.33, PZ0.01). Conclusion:Different initial doses of L-T4 within the range of 10–15 mg/kg per die provide similar outcomes in growth and neurocognitive development in CH patients.