Parental Origin of the X-Chromosome Does Not Influence Growth Hormone Treatment Effect in Turner Syndrome

2012 ◽  
Vol 97 (7) ◽  
pp. E1241-E1248 ◽  
Author(s):  
Marie Devernay ◽  
Diana Bolca ◽  
Lamia Kerdjana ◽  
Azzedine Aboura ◽  
Bénédicte Gérard ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
X Chromosome ◽  
Treatment Effect ◽  
Hormone Treatment ◽  
Population Based ◽  
First Year ◽  
Parental Origin ◽  
Gh Treatment ◽  
Height Gain ◽  
Previously Treated

Abstract Context: The parental origin of the intact X-chromosome has been reported to affect phenotype and response to GH treatment in Turner syndrome (TS). Objective: Our objective was to evaluate the influence of the parental origin of the X-chromosome on body growth and GH treatment effect in TS. Design and Setting: We conducted a population-based cohort study of TS patients previously treated with GH. Participants: Participants included patients with a nonmosaic 45,X karyotype; 556 women were identified as eligible, 233 (49%) of whom participated, together with their mothers. Data were analyzed for 180 of these patients. Main Outcome Measures: We performed fluorescence in situ hybridization analysis to exclude mosaicism and microsatellite analysis of nine polymorphic markers in DNA from the patients and their mothers. The influence on growth and effect of GH were analyzed by univariate and multivariate methods. Results: The X-chromosome was of paternal origin (Xpat) in 52 (29%) of 180 and of maternal origin (Xmat) in 128 (71%) of 180 patients. Height gain from the start of GH treatment to adult height was similar in Xmat and Xpat patients (+2.1 ± 0.9 vs. +2.2 ± 0.8 TS sd score, P = 0.45). The lack of influence of parental origin of the X-chromosome was confirmed in multivariate analysis. Parental origin of the X-chromosome also had no effect on the other growth characteristics studied, including growth velocity during the first year on GH treatment. Patient height was correlated with the heights of both parents and was not influenced by the parental origin of the X-chromosome. Conclusion: In this, the largest such study carried out to date, the parental origin of the X-chromosome did not alter the effect of GH treatment or affect any other features of growth in TS.

scholarly journals Is a Two-Year Growth Response to Growth Hormone Treatment a Better Predictor of Poor Adult Height Outcome Than a First-Year Growth Response in Prepubertal Children With Growth Hormone Deficiency?

2021 ◽  
Vol 12 ◽  
Author(s):  
Saartje Straetemans ◽  
Raoul Rooman ◽  
Jean De Schepper
Keyword(s):  
Growth Hormone ◽  
Growth Response ◽  
Adult Height ◽  
Poor Response ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
First Year ◽  
Gh Treatment ◽  
Height Gain ◽  
Design And Methods

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS <−2.0, or (2) nAH SDS minus mid-parental height SDS <−1.3, or (3) total ΔHt SDS <1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.ResultsEleven percent of the cohort had a total ΔHt SDS <1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS <1.0 had an AUC >70%. First-year ΔHt SDS <0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.

scholarly journals Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001

2002 ◽  
pp. 625-633 ◽  
Author(s):  
MB Ranke ◽  
CJ Partsch ◽  
A Lindberg ◽  
HG Dorr ◽  
M Bettendorf ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Adult Height ◽  
Bone Age ◽  
First Year ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Height Gain ◽  
Puberty Onset

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

Machine learning-based prediction of response to growth hormone treatment in Turner syndrome: the LG Growth Study

2020 ◽  
Vol 33 (1) ◽  
pp. 71-78
Author(s):  
Mo Kyung Jung ◽  
Jeesuk Yu ◽  
Ji-Eun Lee ◽  
Se Young Kim ◽  
Hae Soon Kim ◽  
...  
Keyword(s):  
Machine Learning ◽  
Growth Hormone ◽  
Prediction Model ◽  
Turner Syndrome ◽  
Multiple Regression ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
First Year ◽  
Growth Study ◽  
Gh Treatment

AbstractBackgroundGrowth hormone (GH) treatment has become a common practice in Turner syndrome (TS). However, there are only a few studies on the response to GH treatment in TS. The aim of this study is to predict the responsiveness to GH treatment and to suggest a prediction model of height outcome in TS.MethodsThe clinical parameters of 105 TS patients registered in the LG Growth Study (LGS) were retrospectively reviewed. The prognostic factors for the good responders were identified, and the prediction of height response was investigated by the random forest (RF) method, and also, multiple regression models were applied.ResultsIn the RF method, the most important predictive variable for the increment of height standard deviation score (SDS) during the first year of GH treatment was chronologic age (CA) at start of GH treatment. The RF method also showed that the increment of height SDS during the first year was the most important predictor in the increment of height SDS after 3 years of treatment. In a prediction model by multiple regression, younger CA was the significant predictor of height SDS gain during the first year (32.4% of the variability). After 3 years of treatment, mid-parental height (MPH) and the increment of height SDS during the first year were identified as significant predictors (76.6% of the variability).ConclusionsBoth the machine learning approach and the multiple regression model revealed that younger CA at the start of GH treatment was the most important factor related to height response in patients with TS.

scholarly journals Clinical Significance of the Parental Origin of the X Chromosome in Turner Syndrome

2007 ◽  
Vol 92 (3) ◽  
pp. 846-852 ◽  
Author(s):  
Liora Sagi ◽  
Nehama Zuckerman-Levin ◽  
Aneta Gawlik ◽  
Lucia Ghizzoni ◽  
Atilla Buyukgebiz ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Clinical Significance ◽  
X Chromosome ◽  
Parental Origin

Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature

1994 ◽  
Vol 131 (3) ◽  
pp. 246-250 ◽  
Author(s):  
Jan Åman ◽  
Sten Rosberg ◽  
Kerstin Albertsson-Wikland
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Growth Hormone Treatment ◽  
Gh Deficiency ◽  
Hormone Treatment ◽  
Glucose Disposal ◽  
First Year ◽  
Gh Treatment ◽  
Prepubertal Boys

Aman J. Rosberg S, Albertsson-Wikland K. Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature. Eur Endocrinol 1994;131:246–50. ISSN 0804–4643 The purpose of this study was to evaluate the effect on insulin secretion and glucose metabolism of daily growth hormone (GH) treatment, 0.1 U/kg. for up to 3 years in 42 short prepubertal boys without GH deficiency. Their median height standard deviation (sd) score increased from −2.7 to −1.7, whereas their weight for height sd score was unchanged after 3 years of treatment. Fasting plasma glucose concentrations were unchanged, but median fasting insulin concentrations increased from 6.0 mU/l before treatment to 7.8 mU/l (p < 0.05) after the first year. No further increase was seen during the second or third years. The median insulin area under the curve 10–60 min after an intravenous glucose tolerance test increased from 480 mU·1−1·min−1 before treatment to 799 mU·1−1 · min−1 (p < 0.05) after 1 year. The median glucose disposal rate (K value) before GH treatment, 2.2%/min, was unchanged after 1 year of treatment. A significant positive correlation was found between the change in the height sd score and the change in fasting insulin concentration during the first (r = 0.45; p < 0.01) and second (r = 0.56; p < 0.05) years of GH treatment. It was concluded that GH treatment in prepubertal children without GH deficiency caused a moderate increase in fasting and stimulated insulin concentrations during the first year of treatment. There was no further change during the following years of treatment, and there were no negative effects on fasting plasma glucose concentrations or glucose disposal rates. The increase in insulin concentration was related positively to the growth response. Jan Åman, Department of Pediatrics, Örebro Medical Centre Hospital, S-701 85 Örebro, Sweden

scholarly journals Growth Hormone Treatment in Short Children Born Prematurely—Data from KIGS

2011 ◽  
Vol 96 (6) ◽  
pp. 1687-1694 ◽  
Author(s):  
Margaret C. S. Boguszewski ◽  
Hanna Karlsson ◽  
Hartmut A. Wollmann ◽  
Patrick Wilton ◽  
Jovanna Dahlgren
Keyword(s):  
Birth Weight ◽  
Gestational Age ◽  
Growth Response ◽  
Growth Failure ◽  
Hormone Treatment ◽  
Height Velocity ◽  
First Year ◽  
Gh Treatment ◽  
Provocative Test ◽  
Short Children

Context: Children born prematurely with growth failure might benefit from GH treatment. Objectives: The aim was to evaluate the first year growth response to GH treatment in short children born prematurely and to identify predictors of the growth response. Design/Patients: A total of 3215 prepubertal children born prematurely who were on GH treatment were selected from KIGS (The Pfizer International Growth Database), a large observational database. They were classified according to gestational age as preterm (PT; 33 to no more than 37 wk) and very preterm (VPT; &lt;33 wk), and according to birth weight as appropriate for gestational age [AGA; between −2 and +2 sd score (SDS)] and small for gestational age (SGA; −2 SDS or below). Results: Four groups were identified: PT AGA (n = 1928), VPT AGA (n = 629), PT SGA (n = 519), and VPT SGA (n = 139). GH treatment was started at a median age of 7.5, 7.2, 6.7, and 6.0 yr, respectively. After the first year of GH treatment, all four groups presented a significant increase in weight gain and height velocity, with a median increase in height SDS higher than 0.6. Using multiple stepwise regression analysis, 27% of the variation in height velocity could be explained by the GH dose, GH peak during provocative test, weight and age at GH start, adjusted parental height, and birth weight SDS. The first year growth response of the children born PT and SGA could be estimated by the SGA model published previously. Conclusion: Short children born prematurely respond well to the first year of GH treatment. Long-term follow-up is needed.

scholarly journals Karyotype Abnormalities in the X Chromosome Predict Response to the Growth Hormone Therapy in Turner Syndrome

2021 ◽  
Vol 10 (21) ◽  
pp. 5076
Author(s):  
Jakub Kasprzyk ◽  
Marcin Włodarczyk ◽  
Aleksandra Sobolewska-Włodarczyk ◽  
Katarzyna Wieczorek-Szukała ◽  
Renata Stawerska ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
X Chromosome ◽  
Growth Hormone Therapy ◽  
Marker Chromosome ◽  
Height Velocity ◽  
First Year ◽  
Rhgh Therapy ◽  
Different Types ◽  
Second Year

Short stature is characteristic for Turner syndrome (TS) patients, and particular karyotype abnormalities of the X chromosome may be associated with different responsiveness to recombinant human GH (rhGH) therapy. The aim of the study was to analyze the effect of different types of TS karyotype abnormalities on the response to rhGH therapy. A total of 57 prepubertal patients with TS treated with rhGH with a 3 year follow-up were enrolled in the study and categorized according to their karyotype as X monosomy (n = 35), isochromosome (n = 11), marker chromosome (n = 5), or X-mosaicism (n = 6). Height and height velocity (HV) were evaluated annually. In the first year, all groups responded well to the therapy. In the second year, HV deteriorated significantly in X-monosomy and isochromosome in comparison to the remaining two groups (p = 0.0007). After 3 years of therapy, all patients improved the score in comparison to their target height, but better outcomes were achieved in patients with marker chromosome and X-mosaicism (p = 0.0072). X-monosomy or isochromosome determined a poorer response during the second and third year of rhGH therapy. The results of the study indicate that the effects of rhGH therapy in patients with TS may depend on the type of TS karyotype causing the syndrome.

scholarly journals Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens

2003 ◽  
Vol 88 (3) ◽  
pp. 1119-1125 ◽  
Author(s):  
Yvonne K. van Pareren ◽  
Sabine M. P. F. de Muinck Keizer-Schrama ◽  
Theo Stijnen ◽  
Theo C. J. Sas ◽  
Maarten Jansen ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Low Dose ◽  
Final Height ◽  
Height Velocity ◽  
Chronological Age ◽  
First Year ◽  
Bone Maturation ◽  
Gh Treatment ◽  
Group A ◽  
Group B

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m2·d; ∼0.045 mg/kg/d), group B (first year, 4 IU/m2·d; thereafter 6 IU/m2·d), or group C (first year, 4 IU/m2·d; second year, 6 IU/m2·d; thereafter, 8 IU/m2·d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 ± 0.7 yr, low dose micronized 17β-estradiol was given orally. After a mean duration of GH treatment of 8.6 ± 1.9 yr, FH was reached at a mean age of 15.8 ± 0.9 yr. FH, expressed in centimeters or sd score, was 157.6 ± 6.5 or −1.6 ± 1.0 in group A, 162.9 ± 6.1 or −0.7 ± 1.0 in group B, and 163.6 ± 6.0 or −0.6 ± 1.0 in group C. The difference in FH in centimeters, corrected for height sd score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P &lt; 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P &lt; 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, −1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH sd score, more than −2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH sd score: GH dose, height sd score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.

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