Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial.
BACKGROUND
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.


METHODS
This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003).


METHODS
The study was conducted at 11 U.S. pediatric endocrine centers.


METHODS
Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled.


METHODS
Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr.


METHODS
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 (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.


CONCLUSIONS
Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.
Davenport
Marsha L
ML
Division of Pediatric Endocrinology, University of North Carolina, CB 7039, 3341 Medical Biomolecular Research Building, Chapel Hill, North Carolina 27599-7039, USA. mld@med.unc.edu
Crowe
Brenda J
BJ
Travers
Sharon H
SH
Rubin
Karen
K
Ross
Judith L
JL
Fechner
Patricia Y
PY
Gunther
Daniel F
DF
Liu
Chunhua
C
Geffner
Mitchell E
ME
Thrailkill
Kathryn
K
Huseman
Carol
C
Zagar
Anthony J
AJ
Quigley
Charmian A
CA
D000365:Age Determination by Skeleton; D001846:Bone Development / Q000187:drug effects; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D014424:Turner Syndrome / Q000097:blood / Q000188:drug therapy*
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I