Growth hormone (GH) is commonly used during childhood to treat short stature in Silver-Russell syndrome (SRS), but final height and long-term body mass index (BMI) data are limited.
Objective: To evaluate height and BMI in older individuals with molecularly confirmed SRS and compare those previously treated with GH to those untreated.
Methods: Growth data on individuals aged ≥13 years with SRS were evaluated from UK, French and German cohorts. Height and BMI values were converted to age- and sex-specific standard deviation scores (SDS) using country-specific reference data. Participants were stratified into two groups according to prior GH exposure and compared using the Mann-Whitney U test.
Results: 71 individuals (40 females, 31 males) aged 13.269.7 years (median 22.0) were studied. Molecular diagnoses included loss of methylation at H19/IGF2 in 80.3%, maternal uniparental disomy for chromosome 7 in 16.9% and IGF2 mutation in 2.8%. 77.5% received GH with a median treatment duration of 7.10 years (IQR 3.96 to 11.00). The median time since GH discontinuation was 9.97 years (IQR 2.68 to 15.94). Median early height SDS in the GH-untreated and GH-treated groups were −2.91 (IQR −3.62 to −2.40) and −3.46 (IQR −5.15 to −2.76) respectively (P=0.055). Median height gain from early height SDS to final height SDS was 0.53 (IQR −0.13 to 1.37) in the GH-untreated group and 1.53 (IQR 0.80 to 2.52) in the GH-treated group (P=0.006). The median final height SDS of GH-untreated and GH-treated individuals were −2.74 (IQR −3.36 to −1.13) and −2.22 (IQR −3.66 to −1.16) respectively (P=0.720). The median change in BMI from early BMI SDS to final BMI SDS was 3.58 (IQR 1.85 to 5.18) in the GH-untreated group and 1.95 (IQR 0.76 to 2.69) in the GH-treated group (P=0.005). The median BMI SDS of GH-untreated and GH-treated individuals were 1.66 (IQR −0.73 to 2.03) and −1.10 (IQR −1.80 to 0.00) respectively (P=0.002). In the GH-untreated group there was a positive correlation between duration of time since GH treatment and BMI SDS (Spearmans rank correlation coefficient 0.341, P=0.027).
Conclusions: Although final height was comparable in GH-treated versus GH-untreated individuals, height gain was significantly greater in GH-treated individuals who were shorter in childhood. We speculate that strategies to prevent rapid bone-age maturation during puberty may further optimize the benefit of GH treatment until final height. Following GH discontinuation, treatment was associated with lower BMI and lower gain in BMI, suggesting a long-term effect.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology