Growth Hormone In Turner Syndrome Research Articles

Growth hormone therapy in a girl with Turner syndrome – An experience from Bangladesh

Turner syndrome (TS) is the most common sex chromosome abnormality in females. Short stature and hypogonadism are principal signs of TS. Turner syndrome is well-established. There have been studies that have evaluated the benefits of growth hormone in TS with significant benefit in adult height. A 9-year 11 months-old girl who presented to the Paediatric Endocrinologist, with complaint of not growing according to her age. Her growth was noticed to be slow from early age but her parents initially thought it was normal. They however became worried when she was not growing yet to start pubertal development. Her parents eventually took her to this referral hospital for further evaluation and management.

Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome

Short stature and thyroid autoimmunity are common comorbidities in Turner syndrome (TS). Recombinant human growth hormone (rhGH) significantly improves height growth in TS individuals. This study aims to investigate the association of thyroid autoimmunity and the response to rhGH treatment in TS patients. Medical records of 494 patients with TS were reviewed. Among 126 patients who regularly tested for thyroid autoantibodies, 108 patients had received rhGH treatment. Clinical characteristics, including karyotype and the presence of autoimmune thyroid diseases, as well as rhGH treatment records were analyzed. Height velocity (HV) of patients with or without thyroid autoimmunity was compared to assess the response to rhGH treatment. For patients who developed thyroid autoantibodies during rhGH treatment, HV before and after antibody presence were compared. 45XO monosomy presented in 36% (176/496) of patients. 42.1% of patients (53/126) had elevated circulating anti-thyroid peroxidase antibody and anti-thyroglobulin antibody. In 108 patients who received rhGH treatment, HVs were significantly correlated to age, height, weight and BMI at the initiation of treatment. For patients who developed thyroid autoantibodies during rhGH treatment, HVs after thyroid autoantibody presence significantly decreased compared with HVs before thyroid autoantibody detection (n=44, p=0.0017). Our data suggested that in TS patients who developed thyroid autoantibodies during rhGH treatment, the response to rhGH is negatively associated with the development of thyroid autoimmunity.

Growth and growth hormone in Turner syndrome: Looking back, looking ahead.

Short stature is the most ubiquitous feature of Turner syndrome (TS). Today, many girls with TS are treated with recombinant human growth hormone (GH) to accelerate growth in childhood and to improve adult height. Here, we will review the history of our understanding of growth in TS, reflect on the path of clinical trials ultimately leading to regulatory approval for clinical use of GH, discuss factors associated with growth outcomes and survey the current unanswered questions about growth and GH in TS.

Safety of Growth Hormone for Children with Turner Syndrome

Endocrinology| June 01 2008 Safety of Growth Hormone for Children with Turner Syndrome AAP Grand Rounds (2008) 19 (6): 69–70. https://doi.org/10.1542/gr.19-6-69 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Safety of Growth Hormone for Children with Turner Syndrome. AAP Grand Rounds June 2008; 19 (6): 69–70. https://doi.org/10.1542/gr.19-6-69 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: somatotropin, somatropin, turner's syndrome Source: Bolar K, Hoffman AR, Maneatis T, et al. Long-term safety of recombinant human growth hormone in Turner syndrome. J Clin Endocrinol Metab. 2008;93(2):344–351; doi:10.1210/ jc.2007-1723. To assess the safety of treating children with Turner Syndrome (TS) with recombinant human growth hormone (rhGH), researchers from the University of Texas-Galveston, Stanford, and Genentech, Inc. reviewed data collected as part of the National Cooperative Growth Study (NCGS). The NCGS is an ongoing project of Genentech. Investigators beginning patients on a Genentech rhGH product are required to provide reports of serious adverse events (AEs) and targeted AEs, irrespective of relationship to rhGH, including malignancy, diabetes mellitus, intracranial hypertension (IH), scoliosis, slipped femoral epiphysis (SCFE), and pancreatitis. For the current study, safety data for 5,220 children with TS and almost 50,000 non-TS patients treated with rhGH from 1985 until 2006 were compared. Age at enrollment was 0.1–21.2 years for TS patients with a mean age of 9.8 years. Safety data were presented in four categories: overall safety including deaths; targeted events associated with rhGH; events associated with TS; and other serious AEs. The incidence of reported serious AEs among patients with TS was 2.2% compared to 2.9% for the non-TS population. The incidence of targeted AEs among the 5,220 TS patients was 8.5% (442) compared with 7.3% in the non-TS population. Seven TS patients died, five from aortic dissection or rupture, a known complication of TS.1,–3 The incidence of events known to be associated with rhGH including IH, SCFE, scoliosis, diabetes, and pancreatitis were all higher in TS patients than in those without TS. The incidence of new-onset malignancies in patients without other risk factors was 0.11% for TS patients compared with 0.06% for non-TS patients. The authors conclude that patients with TS who were treated with rhGH had an increased risk for selected AEs. However, the rate of death from aortic dissection/rupture in TS patients in this study is similar to that found in previous studies of TS patients not receiving growth hormone;1,–3 thus, it is unlikely that rhGH contributed to these patients’ deaths. It is uncertain whether the reported malignancies represent an inherited increased risk in TS patients. The NCGS and similar registries, although focused in the years during rhGH treatment, may provide valuable information regarding the natural history of TS in childhood. Dr. Varma has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. This study, which was organized and supported by Genentech, drew on the largest database of TS individuals in the US. TS is a common chromosomal anomaly which is seen in about 1:2,500 live female births.4 At any given time in the US there are about 50,000 girls and women who are affected by this disorder. Patients with TS are at increased risk for a variety of problems including coarctation of aorta, bicuspid aortic valve, aortic dilation, dissection, and rupture.... You do not currently have access to this content.

Growth Promoting Treatment Normalizes Speech Frequency in Turner Syndrome

To assess objective and subjective voice parameters among Turner syndrome (TS) women in relation to genotype, hearing, growth, and previous treatment with growth hormone (GH) and androgen given that lowering of speaking fundamental frequency (SFF) during treatment is regarded as a negative side effect. Cross-sectional, controlled for karyotype and age. Voice function was studied objectively (SFF) and subjectively (questionnaire) in 117 women with TS. SFF did not differ between treated and nontreated participants or between patients with a spontaneous versus induced puberty. SFF was dependent on karyotype but not age. Subjective voice change was reported four times more often among treated compared with nontreated TS women (odds ratio [OR] = 4.4; 95% confidence interval [CI]: 0.9-20.10), whereas voice and articulation problems were reported three times more often among untreated compared with treated cases (OR = 2.9; 95% CI: 1.0-8.3). Voice symptoms were over-represented among patients having micrognathia (OR = 6.0; 95% CI: 1.6-22.3), hearing loss (OR = 8.6; 95% CI: 1.7-43.1), and monosomy (OR = 6.2; 95% CI: 0.8-36.2) but not among those with an arched palate. When given to TS girls, GH (33-66 microg/kg/d) and androgen (0.05 mg/kg/d) normalized SFF and reduced voice and articulation problems in adulthood. The TS phenotype includes important voice and speech problems, which in turn are associated with hearing problems, although genotypic, monosomic, and isochromosome patients have more voice problems and also more high-pitched voices than mosaic patients. Most TS women, despite their karyotype or age, exhibit a higher frequency of pitched voice than non-TS women.

Growth Hormone in Turner Syndrome: Twenty Years after, What Can We Tell our Patients?

Growth Hormone in Turner Syndrome: Twenty Years after, What Can We Tell our Patients?

Growth hormone in Turner syndrome

Growth hormone in Turner syndrome

Prediction of Long-Term Response to Recombinant Human Growth Hormone in Turner Syndrome: Development and Validation of Mathematical Models

Prediction of Long-Term Response to Recombinant Human Growth Hormone in Turner Syndrome: Development and Validation of Mathematical Models

Predicting the response to recombinant human growth hormone in Turner syndrome: KIGS models. KIGS International Board. Kabi International Growth Study.

A mathematical model for predicting the growth response in patients with Turner syndrome who received growth hormone (GH) therapy was developed by analysing data from KIGS, the Pharmacia & Upjohn International Growth Database. A model for year 1 of GH therapy explained 46% of the variability of the growth response, with GH dose being the most important of the predictors of height velocity. In years 2-4 of therapy, height velocity during the previous year was the most important predictor, suggesting that an individual's initial response to GH may determine the height outcome of treatment. Additional predictors of height velocity in years 1-4 of GH therapy included age (negative), weight SDS and additional treatment with oxandrolone. The predictions in all 4 years were highly accurate, as indicated by the low error SDs. However, relatively low predictive power (R) during years 2-4 of treatment suggests the models are missing other parameters that would explain more of the variability of the growth response. These growth prediction models could help clinicians to design individualized treatment regimens, provide realistic expectations of therapy outcomes, and adjust treatment on the basis of detected differences between observed and predicted height velocities.

Growth hormone therapy in Turner syndrome--current uncertainties and future strategies.

The effect of growth hormone (GH) on short-to-medium-term growth in girls with Turner syndrome is well-established. However, it is only relatively recently that final height data have become available. This paper reviews 10 reports from Europe (including Sweden, Austria, France, Holland, Belgium and Scotland), Canada, USA and Japan, on final height and near-final height in girls with Turner syndrome receiving GH therapy. An improvement in final height outcome versus projected adult height was found in all the studies, except for the Scottish study, in which the median final height was only 142.6 cm, and the Canadian study, in which the projected adult height was unexpectedly high at 148.2 cm. Although the mean final height was 150 cm or greater in six studies, all 10 showed considerable individual variation in final height with minimum values ranging between 131.5 and 145 cm. These results must be interpreted cautiously since the mean age of starting treatment was relatively late at 9.1-13.1 years. However, the overall modesty and interpatient variability of response to GH in Turner syndrome, and continuing uncertainty as to the role of oxandrolone and the timing of estrogen therapy, emphasizes the need for further research. National and international collaboration in both retrospective and prospective studies are necessary to achieve sufficient data to offset the large number of variables to be analysed. In the UK, the British Society for Paediatric Endocrinology and Diabetes hopes to do a retrospective meta-analysis of final/near-final height outcome, comparing this with midparental and maternal height, as well as projected height and control data. A prospective study with GH dose standardized at 30 IU/m2 per week in the form of daily injections, with randomization to receive oxandrolone or not at 9 years, and estrogen at either 12 or 14 years, is also planned.

Growth Hormone (GH) Treatment in Turner Syndrome (TS) and Predictors of Response: a Comparison between Japan, Sweden, and the UK as Documented in the Kabi Pharmacia International Growth Study (KIGS) Database

Baseline auxology and responses to growth hormone (GH) treatment in girls with Turner syndrome (TS) from three countries, Japan, Sweden and the United Kingdom, were compared, using data from the Kabi Pharmacia International Growth Study (KEGS). Differences were observed between countries in respect to pretreatment height and height velocity, chronological and bone ages at onset of GH, parental and target heights, body proportions, weight-for-height index, birth weight, and peak GH levels in provocation tests.Median values for height velocity in the first 3 year of GH treatment were greatest in Sweden and lowest in Japan. A previously derived model for predicting first year response in TS was applied to data from the 3 countries: there was no difference between the Studentised residuals of observed-predicted height velocities between countries.It was concluded that although there were differences in response to GH between countries, there was no difference in “responsiveness”. The predictive model for first year response was robust but only accounted for 25% of the variability of response; other factors predicting response to GH in TS should be sought.

LONG-TERM EFFECTS OF GROWTH HORMONE, ESTROGEN, OR PLACEBO ON SELF-IMAGE AND BEHAVIOR IN TURNER SYNDROME

Girls with Turner syndrome (TS) are short and lack endogenous estrogen. Our aim in this study was to evaluate the behavioral effects of continuous growth hormone (GH), ethinyl estradiol (E), or placebo (P) treatment in TS girls. Subjects were recruited from an ongoing randomized trial, consisting of 4 TS treatment groups: 1.E (25-50 ng/kg/day until age 12, 100 ng/kg, ages 12-14, 200-800 ng/kg/day above 14), 2. GH (0.1 mg/kg, SQ, tiw), 3. E, as above, plus GH, and 4. P until age 12, followed by E, as above. The psychological assessment (at baseline and yearly intervals) included 2 tests: The Child Behavior Checklist (CBCL), a parental report of social and behavior problems, and the Piers-Harris Self-Concept Scale (child reported), a test of overall self-concept. Results were analyzed from 106 girls with TS, ages 5-16 years, with treatment durations of 0-5 years. Baseline karyotype, age, SES level, and growth rate were similar in all 4 groups. Multiple regressions explored the association between treatment group, duration, and the psychological measures for TS girls treated early (prior to age 11.5) or late (after age 11.5), In the early-treated girls, no associations between type or duration of treatment and the psychological measures were revealed. In the late-treated girls, longer E treatment was associated with improved ratings on the Piers Total self-concept scale (p=.0001). Longer GH treatment was associated with more positive ratings on the intellectual and physical subscales (p=.0001). On the CBCL, longer GH treatment was associated with decreased, negative Internalizing and Externalizing (p=.004) behaviors and improved school functioning (p=.0001). We conclude: (1) for early-treated TS girls, treatment with E, GH, or P had no significant effects on the behavioral variables and (2) for late-treated TS girls, both E and GH treatment was associated with improved behavioral outcomes.

GROWTH HORMONE INSUFFICIENCY IN TURNER SYNDROME: IS BODY WEIGHT THE KEY FACTOR?

The age related decline in spontaneous growth hormone (GH) secretion has been suggested to cause growth failure in girls with Turner syndrome (TS). We studied 23 girls (mean age: 11.1 yrs with 95% confidence intervals (CI) 9.9 to 12.3) diagnosed to have Turner syndrome by karyotype analysis. 15 prepubertal age-matched subjects (mean age: 11.6 yrs with CI 10.4 to 12.8) with growth retardation due to familial short stature and/or constitutional growth delay were chosen as controls. Spontaneous 12-hour nocturnal GH secretion was assessed by RIA at 30 minutes intervals. Plasma IGF-1 levels were determined by RIA after acid-ethanol extraction. In TS, the percentage of ideal body weight was significantly higher than controls (mean: 127.5 with CI 116 to 139 in TS, and 100.3 with CI 96 to 104.5 in controls; P = 0.0005), and correlated with bone age (r= 0.62, P < 0.005). Spontaneous GH secretion was significantly lower in TS than controls (mean: 3.2 ng/ml with CI 2.5 to 3.9 in TS, and 5.4 ng/ml with CI 4.8 to 6.0 in controls; P < 0.0001). No significant difference was found in IGF-1 levels. In controls, GH concentrations correlated with bone age (r= 0.56, P < 0.05), whereas in TS no correlation was found. Interestingly, in TS GH levels negatively correlaled with percentage of ideal body weight (r= - 0.43, P < 0.05). Our results, confirming that obesity is a common finding in girls with TS, at least in the age range of our patients, suggest that overweight might be the key factor in determining the subnormal spontaneous GH secretion. On the basis of our previous observations showing a close inverse relationship between body weight and serum IGFBP-1 levels in TS, it might be hypothesized that obesity, probably by increasing insulin secretion, would reduce IGFBP-1 levels eventually leading to an enhancement of IGF negative feed-back effect on GH secretion.

Growth hormone assessment and short-term treatment with growth hormone in Turner syndrome

Growth hormone assessment and short-term treatment with growth hormone in Turner syndrome

Response to Long-Term Administration of Human in Turner's Syndrome Growth Hormone

Three patients with XO sex chromosome constitutions had human growth hormone (HGH) measurements. Exogenous HGH was given to one patient to observe its effect on linear growth. All patients had normal HGH response to hypoglycemia or arginine maleate stimulation. The growth rate of the treated patient was followed during three one-year periods. During the control period the patient's growth rate was 0.23 cm/month. It increased to 0.5 cm/month while she was receiving HGH, 10 mg/ week. During the last period, she took small doses of estrogenic substances conjugated and grew 0.3 cm/ month. Although the patient with Turner's syndrome is genetically destined to be short, growth may be stimulated in some patients with exogenous HGH.