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Cited by 147Growth Hormone and Insulin-like Growth FactorsGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesHypothalamic control of reproductive hormones

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

Davenport, Marsha L., Crowe, Brenda J., Travers, Sharon H., Rubin, Karen, Ross, Judith L., Fechner, Patricia Y., Gunther, Daniel F., Liu, Chunhua +5 more·2007·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2006-2874
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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, 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 mug/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 (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.

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  • Only six RCTs have compared GH treatment with concurrent non-treatment or placebo control for at least one year.

    “Despite numerous studies of GH treatment in TS, only six randomized, controlled trials (RCTs) have compared GH treatment with a concurrent non-treatment or placebo control for at least one year157-162”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [162]

  • Younger age at treatment initiation, including at least 4 years of treatment prior to puberty, is associated with greater GH treatment effect.

    “Younger age at treatment initiation,158,162,163 including at least 4 years of treatment prior to puberty,175,179,180 is associated with greater GH treatment effect.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [162]

  • Factors predictive of taller adult height include taller baseline height, tall parental heights, younger age at initiation, longer duration of treatment, and higher GH dose.

    “Overall, factors predictive of taller adult height include taller baseline height prior to GH initiation, tall parental heights (ie, mid-parental height), younger age at initiation of therapy, longer duration of treatment (especially pre-pubertal treatment duration) and higher GH dose.162,171,175,176”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [162]

  • Early GH treatment in TS prevents further growth failure and provides the opportunity to maintain height within the age-appropriate normal range.

    “Early GH treatment in TS prevents further growth failure162,163,180 and provides the opportunity to maintain height within the age-appropriate normal range.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [162]

  • Multiple lines of evidence have demonstrated relative IGF-I resistance in girls with TS.

    “multiple lines of evidence have demonstrated relative IGF-I resistance in girls with TS.148-151,162”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [162]

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Authors
Davenport, M. L., Crowe, B. J., Travers, S. H., Rubin, K., Ross, J. L., Fechner, P. Y., Gunther, D. F., Liu, C., Geffner, M. E., Thrailkill, K., Huseman, C., Zagar, A. J., & Quigley, C. A.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University of Lilly Research Laboratories (B.J.C., C.L., A.J.Z., C.A.Q.), Indianapolis, Indiana 46285
  • University of Colorado Denver (US)
  • Connecticut Children's Medical Center (US)
  • Thomas Jefferson University (US)
  • Seattle Children's Hospital (US)
  • Children's Hospital Los Angeles (US)
  • University of Arkansas for Medical Sciences (US)
  • Children's Mercy Hospital (US)
Corresponding author
Davenport, Marsha L.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2007-09-01
Volume
92
Issue
9
Pages
3406-3416
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2006-2874
OpenAlex
W2063265780
Cited by
147
References
52
Citations by year
2026: 2 · 2025: 1 · 2024: 10 · 2023: 8 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 11 · 2014: 5 · 2013: 7 · 2012: 8
FWCI
8.77
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eli Lilly and Company
  • Pfizer
  • Bunning Food Allergy Institute, Ann and Robert H. Lurie Children's Hospital of Chicago
  • University of Washington
  • Thomas Jefferson University
  • Seattle Children's Research Institute
  • Children's Mercy Hospital
  • Connecticut Children's Medical Center
  • Insmed
  • Novo Nordisk
  • National Institutes of Health (RR-00046)
  • Genentech
  • Gillings School of Public Health
  • University of North Carolina at Chapel Hill
  • National Center for Research Resources (RR00046, M01RR000046, RR00037)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
Turner syndrome, growth hormone therapy, short stature, toddlers, height SDS, height velocity, mid-parental height, treatment response prediction, recombinant human growth hormone
MeSH terms
Age Determination by Skeleton, Bone Development, Child, Preschool, Female, Growth Disorders, Humans, Infant, Insulin-Like Growth Factor I, Turner Syndrome, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor Binding Protein 3, Human Growth Hormone

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