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.

Growth Hormone Treatment of Girls With Turner Syndrome: The National Cooperative Growth Study Experience

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 479-481
Author(s):  
Leslie Plotnick ◽  
Kenneth M. Attie ◽  
Sandra L. Blethen ◽  
Judy P. Sy
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Adult Height ◽  
Standard Deviation Score ◽  
Response To Treatment ◽  
Growth Study ◽  
Duration Of Treatment ◽  
Gh Treatment ◽  
Recombinant Growth Hormone ◽  
National Cooperative

Objective. To evaluate growth rate and adult height with recombinant growth hormone (GH) treatment in girls with Turner syndrome (TS) and predictors of their growth response. Methods. Data on girls with TS who were treated with GH in the National Cooperative Growth Study (NCGS) were evaluated. As of January 1997, there were 2798 girls with TS in the NCGS database, 2652 of whom had not previously received GH. Follow-up data on growth were available for 2475 subjects, and data on adult height were available for 622. Results. The average age of girls with TS at enrollment in the NCGS was 10.1 ± 3.6 years. These patients had severely short stature compared with that of unaffected American girls (height, 118.5 ± 16.5 cm; height standard deviation score [SDS], −3.1 ± 0.9), but their heights were typical of those of American girls with TS (TS-specific height SDS, 0.01 ± 0.9). Treatment with GH for an average duration of 3.2 ± 2.0 years resulted in an increase in height SDS of 0.8 ± 0.7 compared with unaffected girls and of 1.2 ± 0.8 compared with TS standards. Growth rates increased from 4.0 ± 2.3 cm/year before treatment to 7.5 ± 2.0 cm/year after 1 year of treatment. Duration of treatment with GH was the strongest predictor of change in height SDS. After 6 to 7 years of treatment with GH, there was a cumulative change of 2.0 in mean height SDS. The 622 girls who reached adult height were older when they began taking GH. Their mean height gain over pre-GH projected height was 6.4 ± 4.9 cm after 3.7 ± 1.9 years of treatment. Their adult height was 148.3 ± 5.6 cm. Conclusions. Although the response to treatment with GH varied, it was associated with highly significant gains in growth and adult height in girls with TS. Duration of treatment with GH was the most important variable predicting adult height.

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

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

2018 ◽  
Vol 90 (3) ◽  
pp. 169-180 ◽  
Author(s):  
Roland Pfäffle ◽  
Christof Land ◽  
Eckhard Schönau ◽  
Paul-Martin Holterhus ◽  
Judith L. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Standard Deviation Score ◽  
Measurement Data ◽  
International Study ◽  
Hormone Treatment ◽  
Height Velocity ◽  
Growth Disorders ◽  
Gh Treatment ◽  
The Usa

Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged.

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 &lt;−2.0, or (2) nAH SDS minus mid-parental height SDS &lt;−1.3, or (3) total ΔHt SDS &lt;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 &lt;1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS &lt;1.0 had an AUC &gt;70%. First-year ΔHt SDS &lt;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.

Growth hormone treatment and bone mineral density in pediatric patients with Prader–Willi syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yuji Oto ◽  
Nobuyuki Murakami ◽  
Takeshi Inoue ◽  
Keiko Matsubara ◽  
Sohei Saima ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Bone Mineral ◽  
Pediatric Patients ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
Prader Willi Syndrome ◽  
Mineral Density ◽  
Gh Treatment ◽  
Total Body

Abstract Objectives Previous reports indicate that growth hormone (GH) treatment for Prader–Willi syndrome (PWS) improves bone mineral density (BMD) only when initiated at a young age and not when initiated in adulthood. However, there are no data on BMD during long-term GH treatment of Japanese children and adolescents with PWS. Thus, this study aimed to investigate BMD changes among patients with PWS, who were undergoing GH treatment from childhood to adolescence. Methods Sixty-seven pediatric patients with PWS who had GH treatment initiated during childhood between January 2003 and June 2020 were evaluated. To avoid underestimation, we used total body BMD, which was evaluated using dual-X-ray absorptiometry adjusted for the BMD z-score using patient height, sex, and age. Results In both sexes, age was negatively correlated with the BMD-standard deviation score (SDS) (male: r=−0.156 [p=0.042]; female: r=−0.197 [p=0.043]), which started to decrease in childhood. Conclusions The BMD-SDS of patients with PWS decreases gradually despite GH treatment. As there are no clear recommendations about monitoring of bone health in patients with PWS, further studies are needed to improve the guidelines for screening of BMD and treatment of patients with PWS.

scholarly journals Impact of growth hormone treatment on children’s height

2014 ◽  
Vol 54 (6) ◽  
pp. 318
Author(s):  
Nur Rochmah ◽  
Muhammad Faizi
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Growth Hormone Treatment ◽  
Body Height ◽  
Hormone Treatment ◽  
Post Treatment ◽  
Hormone Deficiency ◽  
Duration Of Treatment ◽  
Height Measurement ◽  
Gh Treatment

Background The use of growth hormone (GH) is a routinetreatment for growth hormone deficiency (GHD), small forgestational age (SGA), and Turner syndrome (TS). During thetreatment, height measurement at regular intervals is a vital stepto assess success. To date, there have been no previous studieson GH treatment in Dr. Soetomo Hospital, Surabaya, the referralhospital in East Indonesia.Objective To compare body height between pre- and post-growthhormone treatment in pediatric patients.Method This study was a non-randomized, pre-post clinical trialperformed at Dr. Soetomo Hospital, Surabaya. The prospectivecohort was accessed during January 2008-June 2013. Theinclusion criteria was GH treatment for more than 3 months.Clinical data on GH treatment, including diagnosis, age, heightpre-and post-treatment, height gain, duration of treatment, andparental satisfaction were collected. Two-tailed, paired T-test andPearson’s test were used for statistical analyses.Result Nineteen patients underwent GH treatment during thestudy period, but only twelve patients had complete data and wereincluded in the study. Eight subjects were female. Subjects’ meanage was 11 (range 8-15) years. Nine patients had GHD, 2 hadTS, and 1 had SGA. Mean pre-treatment height was 121.05 cm,while mean post-treatment height was 130.5 cm. Mean durationof treatment was 10.5 (range 3-30) months. Mean height gainwas 0.8 cm/month in GHD and SGA cases, and 0.78 cm/monthfor the TS cases. Eleven parents reported satisfaction with theresults of GH treatment in their children. There is significantdiffrent between pre- and post-treatment (P=0.001). Pearson’scorrelation test (r=0.90) revealed a strong correlation betweengrowth hormone treatment and height gain.Conclusion Growth hormone treatment has impact on heights inGH defficiency, Turner syndrome, and small for gestational age.

scholarly journals Childhood growth hormone treatment in women with Turner syndrome - benefits and adverse effects

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tomasz Irzyniec ◽  
Wacław Jeż ◽  
Katarzyna Lepska ◽  
Izabela Maciejewska-Paszek ◽  
Jakub Frelich
Keyword(s):  
Growth Hormone ◽  
Adverse Effects ◽  
Turner Syndrome ◽  
Sex Chromosome ◽  
Initial Period ◽  
Growth Failure ◽  
Hormone Treatment ◽  
Treated Group ◽  
Gh Treatment ◽  
Childhood Growth

Abstract Turner syndrome (TS) is characterized by the partial or complete loss of one sex chromosome and results in growth failure, gonadal insufficiency and cardiac anomalies. Treatment with growth hormone (GH) during childhood has indisputable benefits when taking into account the low stature of TS women. Medical records and biochemical findings of 33 TS women treated with GH in childhood (GH+) were compared to those of 124 TS women who did not receive GH (GH−). It seems that the GH-treated group might have had a more severe initial phenotype than the untreated group, as evidenced by higher FSH, more feeding issues in infancy, more lymphedema cases and urinary system malformations. GH+ women were significantly taller and had a better lipid profile and lower prevalence of arterial hypertension than GH− . However, they also had lower thrombocyte counts, a greater prevalence of retrognathism and nail anomalies, especially when the GH treatment was delayed. Long-term GH use was not as effective for growth as GH treatment during the initial period and seemed to have resulted in elevated creatinine levels. GH treatment in childhood has benefits in adulthood; however, adverse effects may occur, especially in individuals with treatment that is delayed or is too long.

Growth and Adult Height in Girls With Turner Syndrome Following IGF-1 Titrated Growth Hormone Treatment

2020 ◽  
Vol 105 (8) ◽  
pp. 2566-2574
Author(s):  
Amanda Cleemann Wang ◽  
Casper P Hagen ◽  
Leila Nedaeifard ◽  
Anders Juul ◽  
Rikke Beck Jensen
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Real World ◽  
Adult Height ◽  
Standard Deviation Score ◽  
Fixed Dose ◽  
Dose Titration ◽  
Gh Treatment ◽  
Real World Evidence ◽  
Tertiary Center

Abstract Context Girls with Turner syndrome (TS) suffer linear growth failure, and TS is a registered indication for growth hormone (GH) treatment. GH is classically dosed according to body weight, and serum insulin-like growth factor-1 (IGF-1) concentrations are recommended to be kept within references according to international guidelines. Objective To assess the effect of long-term GH treatment in girls with TS following GH dosing by IGF-1 titration. Design and setting A retrospective, real-world evidence, observational study consisting of data collected in a single tertiary center from 1991 to 2018. Patients A cohort of 63 girls with TS treated with GH by IGF-1 titration with a median duration of 6.7 years (interquartile range [IQR]: 3.4-9.7 years). Main outcome measures Longitudinal measurements of height, IGF-1, and adult height (AH) following GH treatment were evaluated and compared between the different karyotypes (45,X, 45,X/46,XX, or miscellaneous). Results Using GH dose titration according to IGF-1, only 6% of girls with TS had supranormal IGF-1 levels. Median dose was 33 µg/kg/day (IQR: 28-39 µg/kg/day) with no difference between the karyotype groups. AH was reached for 73% who attained a median AH of 1.25 standard deviation score (SDS) for age specific TS references (IQR: 0.64-1.50 SDS), and a median gain in height (ΔHSDS: AH SDS minus baseline height SDS of TS references) of 0.50 SDS, equal to 3.2 cm (SD 7.68) for all karyotypes. Conclusion Our real-world evidence study suggested that titration of GH dose to keep IGF-1 levels within the normal range resulted in a lower AH gain than in studies where a fixed dose was used.

scholarly journals Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study

2017 ◽  
Vol 102 (9) ◽  
pp. 3195-3205 ◽  
Author(s):  
Charmian A Quigley ◽  
Christopher J Child ◽  
Alan G Zimmermann ◽  
Ron G Rosenfeld ◽  
Leslie L Robison ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Turner Syndrome ◽  
International Study ◽  
Hormone Treatment ◽  
Idiopathic Short Stature ◽  
Growth Disorders ◽  
Gh Treatment ◽  
Increased Risk ◽  
History Of

Abstract Context Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood. Objective To assess mortality in children receiving GH. Design Prospective, multinational, observational study. Setting Eight hundred twenty-seven study sites in 30 countries. Patients Children with growth disorders. Interventions GH treatment during childhood. Main Outcome Measure Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population. Results Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non–GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65). Conclusions No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non–GH-deficient medical conditions.

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