MON-102 Serum Concentrations of FT4 and TSH in the First Six Months of L-Thyroxine Treatment in Infants with Congenital Hypothyroidism: Target Attainment Rates Should Be Improved

Levo-Thyroxine (L-T4) is the medication of choice for treating congenital hypothyroidism (CH). Adequate L-T4 treatment is essential for early neurodevelopment in affected patients. Both under- and overtreatment with L-T4 were associated with long-term adverse neurological outcomes. Based on clinical experience, initial L-T4 dosing does not always result in optimal TSH and FT4 concentrations in all CH patients. The purposes of this study were 1) to quantify FT4 and TSH target attainment rates (TAR) in the first six months of L-T4 treatment in infants with CH, 2) to compare characteristics of patients with FT4 concentrations “OUT of” versus “IN” the target range at first time of monitoring. A multicenter retrospective analysis was conducted in infants born between 1995 and 2018. TSH and FT4 TARs were defined according to the most recent guidelines of the European Society for Paediatric Endocrinology (ESPE), as the percentage of concentrations “in” and “in the upper half” of the corresponding laboratory age-specific reference range for TSH and FT4, respectively. We analyzed a total of 208 TSH and 186 FT4 serum concentrations from 60 patients during the first 6 months of L-T4 treatment. The pretreatment FT4 and TSH serum concentrations (mean±SD) were 8.3±5.7 pmol/L and 338±248 mU/L, respectively. CH severity according to ESPE guidelines was severe, moderate and mild for 32%, 27% and 32% of the patients. Postnatal age (PNA) (mean±SD) at start of treatment was 10±12 days. Starting dose of L-T4 (mean±SD) for severe, moderate and mild CH were 10±4, 10±3, and 7±4 µg/kg/day, respectively. Over the study period, TSH TARs of 63% did not further improve between the first monitoring (mean at 17 days of treatment) and fourth monitoring (mean at 4 months of treatment), while FT4 TARs increased from 22% to 45% paralleled with a decrease of too high FT4 values from 55% to 21%. Comparing patients with FT4 concentrations “OUT of” versus “IN” the target range at first time monitoring (16 versus 18 days after starting treatment; p=0.45), they did not differ in pretreatment FT4 concentrations (p=0.2). In contrast, patients who had FT4 concentrations “OUT of” versus “IN” the target range received first dose of L-T4 at an earlier median PNA (7 versus 16 days; p=0.008), had higher pretreatment mean TSH concentrations (364 versus 181 mU/L; p=0.02) and received a higher mean initial L-T4 dose (10.3 versus 7.1 µg/kg/day; p=0.01). First, our results show that FT4 and TSH target ranges were not reached in all patients in the first six months of treatment. Second, our data suggest that TARs could be improved by individualizing initial L-T4 dosing not only according to pretreatment FT4 but also to pretreatment TSH concentrations. L-T4 dosing optimization is needed in this population.