ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab 2018;103:1459-1469

The ESPE guidelines on CH recommend an initial LT4 dose of 10-15 microgram/kg per day¹. Infants with severe CH, defined by a very low pretreatment TT4 or FT4 concentration, should be treated with the highest initial dose. However, little is known about long-term effects on developmental and anthropometric outcomes in CH children treated with initial high doses (>10 microgram/kg/day).

The strength of this study by Aleksander et al. is the detailed characterization of the participants to provide comprehensive data on intellectual and somatic outcomes. No IQ difference could be found between patients and healthy siblings, considering all possible biases. Further, no difference was detected for any anthropometric or metabolic parameter. Most importantly, thyroid hormone levels during the critical period of the first 24 months had no influence on intellectual outcomes. Additionally, the authors performed a detailed meta-analysis of all available studies evaluating mean IQ in the context of CH severity and LT4 starting dose (<8 microgram/kg/d; 8-10 microgram/kg/d; >10 microgram/kg/d). Complete raw datasets of 4 studies were provided by the principal investigators of those previous studies: Patients with severe CH showed significantly lower IQ than patients with mild/moderate CH if treated with LT4 doses of <8 micrograms/kg/d or 8-10 micrograms/kg/d. Only high dose LT4 treatment was able to protect patients with severe CH from IQ loss.

These important results advocate for high dose LT4 treatment without adverse effects in adult life in accordance with a recent study from New Zealand² and the current ESPE guidelines. Concerns raised recently concerning worse intellectual outcome in CH patients at the age of 11 years after episodes of overtreatment during the first two years of life³ were not confirmed in this study.

1. Léger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, Polak M, Buler G; ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE; Comgemital Hypothyroidism Consensus Conference Group. European Society for Paediatirc Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab 2014;99:363-384.

2. Albert BB, Heather N, Derraik JG, Cutfield WS, Wouldes T, Tregurtha S, Mathai S, Webster D, Jefferies C, Gunn AJ, Hofman PL. Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring. J Clin Endocrinol Metab 2013;98:3663-3670.

3. Bongers-Schokking JJ, Resing WC, de Rijke YB, de Ridder MA, de Muinck Keizer-Schrama SM. Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment? J Clin Endocrinol Metab 2013;98:4499-4506.