Recombinant growth hormone in children and adolescents with Turner syndrome. 2003

C B Cave, and J Bryant, and R Milne
Wessex Institute for Health Research and Development, University of Southampton, Bassett Crescent East, Mailpoint 728, Biomedical Sciences Building, Southampton, UK, SO16 7PX.

BACKGROUND Turner syndrome (TS) affects about one in 1,500 to 2,500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Untreated women are approximately 20-21 cm shorter than normal women within their respective populations. Recombinant human growth hormone (hGH) has been used to increase growth and final height in women who have Turner syndrome. OBJECTIVE To assess the effects of recombinant growth hormone on short-term growth and final height in children and adolescents with Turner syndrome. METHODS Published and unpublished randomised-controlled trials (RCTs) were sought by searching the Cochrane Central Register of Controlled Trials (Central) (2002, Issue 3), Medline (1981 to July 2002), Embase (1980 to June 2002), PubMed (search 30 July, 2002 for entries in last 180 days), Science Citation Index (search 30 July, 2002), BIOSIS (search 30 July, 2002) and Current Controlled Trials (search 30 July, 2002). Article reference lists were assessed for trials and experts and pharmaceutical companies were contacted. METHODS Randomised controlled trials were included if they were carried out in children with Turner Syndrome before achieving final height. Growth hormone had to be administered for a minimum of six months and compared with a placebo or no treatment control condition. A growth or height outcome measure must have been assessed. In addition, in the context of a growth assessment other outcomes reflecting psychological adjustment were also included. METHODS Two reviewers assessed studies for inclusion criteria and for methodological quality. Data were extracted by one reviewer and checked by a second. The main outcomes were final height (in cm or standard deviation score), growth (in velocity or velocity standard deviation score). Additional outcomes included bone age, quality of life, cognitive performance, and adverse effects. To estimate summary treatment effects, data were pooled using a random effects model (when data were sufficient and appropriate to combine) with calculation of weighted mean differences (WMD) for continuous outcomes. RESULTS Four RCTs that included 211 participants after one year of treatment were included. These were described in six publications. Three studies were included in the analyses of growth outcomes (one study did not report any data). Only one trial reported results on final height. This trial reported that average final height in 40 treated women was 146.2 cm and 141.4 cm in 29 untreated women (mean difference (MD) 4.8 cm, 95% CI 2.2 to 7.4). Short-term growth velocity was greater in treated than untreated girls after one year (two trials, weighted mean difference (WMD) 3.3 cm/yr, 95% CI 2.4 to 4.3) after 18 months (one trial, MD 2.6 cm/yr, 95% CI 2.1 to 3.1) and after two years (one trial, MD 1.8 cm/yr, 95% CI 1.3 to 2.3). Results were similar when reported as growth velocity standard deviation scores. Skeletal maturity was not accelerated by treatment with recombinant growth hormone (hGH). Bone age divided by chronological age was approximately one in both treated and untreated groups in one trial after both one and two years of treatment. One trial selectively reported psychological outcomes that suggested that psychological adjustment was better in girls treated with hGH, but selective reporting leaves these results in some doubt. Adverse effects were minimally reported. There is little evidence of serious short-term adverse effects in these trials, but they are underpowered to detect rare adverse effects. CONCLUSIONS Recombinant human growth hormone (hGH) doses between 0.3 - 0.375 mg/kg/wk increase short-term growth in girls with Turner Syndrome (TS) by approximately 3 cm in the first year of treatment and by approximately 2 cm per year after 2 years of treatment. There is little evidence on the effects of hGH on final height. Treatment in one trial increased final height by approximately 5 cm over an untreated control group. Despite this increase, the fated control group. Despite this increase, the final height of treated women was still outside the normal range (more than two standard deviations below the normal population mean). Additional trials of the effects of hGH carried out with control groups until final height is achieved would allow better informed decisions about whether the benefits of hGH treatment outweigh the requirement of treatment over several years at considerable cost.

UI MeSH Term Description Entries
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D001827 Body Height The distance from the sole to the crown of the head with body standing on a flat surface and fully extended. Body Heights,Height, Body,Heights, Body
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D005260 Female Females
D006130 Growth Disorders Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth. Stunted Growth,Stunting,Disorder, Growth,Growth Disorder,Growth, Stunted,Stuntings
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D013006 Growth Hormone A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized. Growth Hormone, Recombinant,Pituitary Growth Hormone,Recombinant Growth Hormone,Somatotropin,Somatotropin, Recombinant,Growth Hormone, Pituitary,Growth Hormones Pituitary, Recombinant,Pituitary Growth Hormones, Recombinant,Recombinant Growth Hormones,Recombinant Pituitary Growth Hormones,Recombinant Somatotropins,Somatotropins, Recombinant,Growth Hormones, Recombinant,Recombinant Somatotropin
D014424 Turner Syndrome A syndrome of defective gonadal development in phenotypic females associated with the karyotype 45,X (or 45,XO). Patients generally are of short stature with undifferentiated GONADS (streak gonads), SEXUAL INFANTILISM, HYPOGONADISM, webbing of the neck, cubitus valgus, elevated GONADOTROPINS, decreased ESTRADIOL level in blood, and CONGENITAL HEART DEFECTS. NOONAN SYNDROME (also called Pseudo-Turner Syndrome and Male Turner Syndrome) resembles this disorder; however, it occurs in males and females with a normal karyotype and is inherited as an autosomal dominant. Bonnevie-Ullrich Syndrome,Gonadal Dysgenesis, 45,X,Gonadal Dysgenesis, XO,Monosomy X,Status Bonnevie-Ullrich,Turner's Syndrome,Ullrich-Turner Syndrome,Bonnevie Ullrich Syndrome,Status Bonnevie Ullrich,Syndrome, Ullrich-Turner,Turners Syndrome,Ullrich Turner Syndrome,XO Gonadal Dysgenesis
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical

Related Publications

C B Cave, and J Bryant, and R Milne
January 1995, The Southeast Asian journal of tropical medicine and public health,
C B Cave, and J Bryant, and R Milne
September 2005, The Journal of clinical endocrinology and metabolism,
C B Cave, and J Bryant, and R Milne
December 2021, BMC endocrine disorders,
C B Cave, and J Bryant, and R Milne
December 2008, Therapeutics and clinical risk management,
C B Cave, and J Bryant, and R Milne
February 2020, Diagnostics (Basel, Switzerland),
C B Cave, and J Bryant, and R Milne
April 1993, The Journal of clinical endocrinology and metabolism,
C B Cave, and J Bryant, and R Milne
October 1996, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity,
C B Cave, and J Bryant, and R Milne
January 1999, Journal of Tongji Medical University = Tong ji yi ke da xue xue bao,
C B Cave, and J Bryant, and R Milne
February 2008, The Journal of clinical endocrinology and metabolism,
Copied contents to your clipboard!