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

Abstract

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, openlabel, 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 μg/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 (R2 = 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 (R2 = 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. Copyright © 2007 by The Endocrine Society.