Growth hormone treatment of early growth failure in toddlers with turner syndrome: A randomized, controlled, Multicenter trial

Context: Typically, growth failure in Turner syndrome ( TS) begins prenatally, and height SD score ( SDS) declines progressively from birth. Objective: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort. Design: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial ( Toddler Turner Study, August 1999 to August 2003). Setting: The study was conducted at 11 U. S. pediatric endocrine centers. Subjects: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled. Interventions: Interventions comprised recombinant GH ( 50 g/kg.d; n = 45) or no treatment ( n = 43) for 2 yr. Main Outcome Measure: The main outcome measure was baselineto-2-yr change in height SDS. Results: Short stature was evident at baseline ( mean length/ height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 ( 1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 ( 0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS ( P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS ( r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone ( R-2 = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data ( 4-month or 1-yr height velocity) in the model ( R-2 = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected. Conclusion: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.