Growth Hormone Treatment of Early Growth Failure in Toddlers with Turner Syndrome: A Randomized, Controlled, Multicenter Trial

• Published in: The journal of clinical endocrinology and metabolism 2007-09, Vol.92 (9), p.3406-3416
• Main Authors: Davenport, Marsha L., Crowe, Brenda J., Travers, Sharon H., Rubin, Karen, Ross, Judith L., Fechner, Patricia Y., Gunther, Daniel F., Liu, Chunhua, Geffner, Mitchell E., Thrailkill, Kathryn, Huseman, Carol, Zagar, Anthony J., Quigley, Charmian A.
• Format: Article
• Language: English
• Subjects: Age Determination by Skeleton; Biological and medical sciences; Bone Development - drug effects; Child, Preschool; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Growth Disorders - blood; Growth Disorders - complications; Growth Disorders - drug therapy; Human Growth Hormone - adverse effects; Human Growth Hormone - therapeutic use; Humans; Infant; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - analysis; Medical sciences; Turner Syndrome - blood; Turner Syndrome - drug therapy; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-2874

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 μg/kg·d; n = 45) or no treatment (n = 43) for 2 yr. Main Outcome Measure: The main outcome measure was baseline-to-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.