Thyroid hormone levels in children with Prader–Willi syndrome: a randomized controlled growth hormone trial and 10-year growth hormone study

Abstract

Abstract Context Several endocrine abnormalities were reported in children with Prader–Willi syndrome (PWS), including hypothyroidism. Growth hormone (GH) treatment may impact the thyroid hormone axis by direct inhibition of T4 or TSH secretion or by increased peripheral conversion of free T4 (FT4) to T3. Objective The objective of this study is to evaluate thyroid function during GH treatment in a large group of children with PWS. Methods Serum FT4, T3, and TSH are measured in a 2-year randomized controlled GH trial (RCT) and 10-year longitudinal GH study (GH treatment with 1.0 mg/m²/day [∼0.035 mg/kg/day]). Results Forty-nine children with PWS were included in the 2-year RCT (median [interquartile range, IQR] age: GH group 7.44 [5.47-11.80] years, control group 6.04 [4.56-7.39] years). During the first 6 months, median (IQR) FT4 standard deviation score (SDS) decreased in the GH group from −0.84 (−1.07 to −0.62) to −1.32 (−1.57 to −1.08) (P < .001) and T3 SDS increased from 0.31 (−0.01-0.63) to 0.56 (0.32-0.79) (P = .08), while in the control group, FT4 and T3 SDS remained unchanged. In our 10-year GH study, 240 children with PWS (median [IQR] age: 1.27 (0.54-4.17) years] were included. Between 2 and 10 years, median (IQR) FT4 SDS remained unchanged, being −0.87 (−0.98 to −0.77) after 2 years and −0.88 (−1.03 to −0.74) after 10 years (P = .13). TSH SDS decreased from −0.35 (−0.50 to −0.21) after 2 years to −0.68 (−0.84 to −0.53) after 10 years (P < .001). Conclusions Our findings suggest that GH treatment decreases FT4 levels, due to increased peripheral conversion of FT4 to T3 in the first months of treatment, but thereafter, FT4 and T3 normalize and remain stable during long-term GH treatment in almost all children and adolescents with PWS.