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Effect of Growth Hormone Therapy on Height in Children With Idiopathic Short Stature
A Meta-analysis
Beth S. Finkelstein, PhD;
Thomas F. Imperiale, MD;
Theodore Speroff, PhD;
Ursula Marrero, MSSA;
Deborah J. Radcliffe, PhD;
Leona Cuttler, MD
Arch Pediatr Adolesc Med. 2002;156:230-240.
Context Use of growth hormone (GH) therapy to promote growth in children with
idiopathic short stature is controversial. A fundamental issue underlying
the controversy is uncertainty about the magnitude of effectiveness of GH
for this condition.
Objective To determine the effect of GH on short- and long-term growth in idiopathic
short stature.
Study Design Systematic review of controlled and uncontrolled studies.
Data Sources MEDLINE (1985-2000), key journals, cross-referencing of bibliographies,
abstract booklets, and experts.
Study Selection and Data Extraction We performed a meta-analysis of all studies satisfying the inclusion
criteria for idiopathic short stature: initial height below the 10th percentile,
normal stimulated GH levels (>10 µg/L), absence of comorbid conditions,
no previous GH therapy, treatment with biosynthetic GH, and inclusion of major
outcome measures.
Primary Outcome Measures Growth velocity and height SD score (number of SDs from mean height
for age and sex) at baseline and after 1 year to evaluate the short-term effect
of GH. Adult height was analyzed to evaluate the long-term effect of GH.
Data Synthesis Ten controlled trials (434 patients) and 28 uncontrolled trials (655
patients) met the inclusion criteria. While baseline growth velocities were
equivalent at baseline, 1-year growth velocity of the GH-treated group significantly
exceeded that of controls by 2.86 cm/y. Similarly, in uncontrolled trials,
growth velocity increased after 1 year, and height SD score increased from -2.72
at baseline to -2.19. In controlled studies, the adult height of the
GH-treated group significantly exceeded controls by 0.84 SD, and in uncontrolled
trials the adult height attained after GH treatment (-1.62 SDs) exceeded
that predicted at baseline (-2.18 SDs). These results suggest an average
gain in adult height of approximately 4 to 6 cm (range, 2.3-8.7 cm) with GH
therapy. Given current treatment costs, this corresponds to more than $35 000
per inch (2.54 cm) gained in adult height in idiopathic short stature.
Conclusions Treatment with GH results in short-term increases in growth for children
with idiopathic short stature, and long-term GH can increase adult height.
These results are fundamental to decisions about GH use and raise questions
about the goals of treatment. Use of GH for idiopathic short stature in clinical
practice will depend on its efficacy in promoting growth and the value of
this effect to families, physicians, and third-party payers.
From the Departments of Pediatrics (Drs Finkelstein, Radcliffe, and
Cuttler and Ms Marrero) and Pharmacology (Dr Cuttler), Rainbow Babies and
Children's Hospital, Case Western Reserve University, Cleveland, Ohio; the
Divisions of Gastroenterology and General Internal Medicine, Indiana University
Medical Center and Roudebush Veterans Medical Center, Indianapolis (Dr Imperiale);
and the Division of Health Services Research, the Departments of Medicine
and Preventive Medicine, Center for Clinical Improvement, Vanderbilt University
Medical Center, Nashville, Tenn (Dr Speroff). Dr Cuttler has been an invited
symposium speaker, participated in multisite clinical studies, consulted,
or participated in basic science research grants for AstraZeneca Pharmaceuticals,
London, England; Eli Lilly & Co, Indianapolis, Ind; Merck and Co, Rahway,
NJ; Novo Nordisk, Bagsværd, Denmark; Genentech, Inc, South San Francisco,
Calif; Pharmacia & Upjohn, Kalamazoo, Mich; Athersys, Cleveland, Ohio;
and Serono, Norwell, Mass
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