Treatment of congenital hypothyroidism – impact of secular changes in levothyroxine initial dose on early growth

Introduction: Newborn screening of congenital hypothyroidism (CH) has enabled early treatment with levothyroxine (LT4), ensuring normal growth and development. The initial LT4 dose recommendation has increased over decades. We evaluated whether the increased LT4 dosing influenced thyroid-stimulating hormone (TSH) and thyroxine (fT4) concentrations, growth, or treatment-related symptoms.
Methods: LT4 doses, TSH, fT4, anthropometrics, and treatment-related symptoms until age two years were evaluated in 172 Finnish CH patients born between 1980 and 2018. The patients were grouped according to birth decade: 1980s (n = 19, mean LT4 starting dose 6.8 µg/kg/day), 1990s (n = 50, 7.4 µg/kg/day), 2000s (n = 59, 9.7 µg/kg/day) and 2010s (n = 44, 10.8 µg/kg/day) 
Results: TSH concentrations were higher during the first two years of life in children born in 1980s compared to children born later. TSH concentrations were often subnormal in children receiving higher LT4 doses (children born in 2000s and 2010s). However, symptoms of overtreatment were uncommon. Linear or head growth showed no differences between the groups during the first two years of life. Although growth was within the normal spectrum, children in all groups were shorter than their target length at two years and their weight-for-length was above the mean through the first two years of life.
Discussion/Conclusion: Current treatment practice with higher LT4 dose normalizes TSH rapidly without significant increase in side effects. However, irrespective of initial LT4 dose, children were shorter than expected at 2 years of age. Effects of different initial LT4 dose on cognitive development urges further investigation. 
