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Major Determinants of Height Development in Turner Syndrome Patients Treated with Growth Hormone: Analysis of 987 Patients from KIGS« Back to Volume 23, Issue 2, June 2007 - Table of Contents It is well known that growth hormone (GH) treatment during childhood can lead to a higher adult height in girls with Turner syndrome (TS). This is a report of 987 girls treated to adulthood or near adult height with recombinant human GH from the KIGS data base. Approximately 5 600 girls with TS have been entered into this registry. Data analyzed for this publication included 908 subjects who had reached near adult height, defined as age >15 years with a height velocity during the last year on GH < 2.0 cm/year. The subjects had all been prepubertal during the first year of treatment and had been treated for at least 4 years with a minimum of 5 injections per week. Puberty was defined at the time when spontaneous breast development occurred (Tanner stage B2) or when estrogen replacement therapy was initiated. The following variables were summarized: 1) status at birth: weight SD score, length SD score, ponderal index; 2) genetic background: mother's height SD score, father's height SD score, midparental height (MPH) SD score, and karyotype; 3) treatment modality: GH dosage per kg of body weight and per kg of ideal body weight (weight for height), frequency of GH injections, and accumulated years of GH treatment; 4) variables at the start of treatment: age, bone age, height SD score, weight SD score, height SD score minus MPH SD score, the peak GH concentration in serum during stimulation tests; and 5) variables at puberty onset: age, bone age, height SD score, weight SD score, height SD score minus MPH SD score. SD scores were calculated as follows: SD score = (patient's measured value minus mean value for age and sex-matched normal subjects) ÷ SD of the value for age- and sex-matched normal subjects. These independent variables were utilized in multiple regression analyses to determine which contributed to height or change in height between the start of treatment and the achievement of near adult height. Age at the onset of GH treatment averaged 9.7 years. The average predicted adult height was 146.1 cm. In most cases the initial average GH dose was 0.27 mg/kg/wk delivered in 7 daily injections. Initial height was -2.4 SDS and had reached -1.9 SDS after 1 year of GH therapy. The median gain in height velocity during this first year was 7.4 cm. The age of onset of puberty was 13.5 years and height at this age was 141.8 cm (-1.4 SDS). The overall gain in height from time GH therapy was started was 21.2 cm or 1.5 SDS. Height gain from the start of puberty to near adult height was 9.4 cm. The average age of patients near adult height was 16.9 years with a bone age of 14.5 years. The median height reached was 151 cm, or median gain of 4.9 above the projected height at the time GH treatment was started. The data also showed that height at near adult height was a function of (in order of importance) 1) height at GH start, 2) responsiveness to GH in the first year of treatment, 3) mid-parental height, 4) age at onset of puberty, 5) age at GH start, and 6) mean dose of GH per week. Each of these parameters were significant at a probability level of p<0.01 and accounted for 67% of the variance in near adult height. The gain in height between start of therapy and near adult height was found to be a function of (in order of importance) 1) age at GH start, 2) GH responsiveness during the first year, 3) age at puberty, 4) mid-parental height, 5) height at GH start, 6) mean dose of GH per week, and 7) birth weight. These factors explain 90% of the variance in near adult height. Of note, karyotype did not enter into the multiple regression analyses. The authors remarked that their observations show that responsiveness to GH during the first year of treatment is the foremost factor in response to height gained during subsequent pre-pubertal years. The data also demonstrated that there is no further gain in relative height after the onset of puberty. They stated that their regression equations support the principal concepts of the current treatment recommendations in TS and further suggest that these equations might be suitable to use as guidelines for daily practice. They cautioned however, that use of such equations might mean that the GH dose and timing at the puberty onset should be adapted to individual patient's responsiveness to GH treatment and that in some cases the GH dose might need to be reduced or discontinued. Editor’s CommentThese data reported from the large KIGS database of girls with TS are both reassuring and disquieting. Clearly GH therapy should be initiated at an early age, regardless of the child's current height. Unfortunately, many girls with TS are not identified until their height falls below the 3rd percentile. The KIGS data suggest that treating these girls at that time while clearly beneficial, is not as beneficial in terms of height gain as treating them shortly after diagnosis regardless of their current height. The data also suggest that higher doses of GH, especially during the first year of treatment, may be of significant benefit to achieving greater adult height. Although the authors have carefully developed regression equations for determining near adult height and height gain, between GH start and near adult height, one must be cautioned that statistically significant contributions to the variance in an outcome variable are meant to be used in populations and may not apply in individual cases and may be inappropriate guides for therapy. William L. Clarke, MD
« Back to Volume 23, Issue 2, June 2007 - Table of Contents
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Volume 26 Number 1
September 2010
www.GGHjournal.com
ISSN 1932-9032
