scholarly journals High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height

2010 ◽  
Vol 162 (4) ◽  
pp. 653-660 ◽  
Author(s):  
S A van Gool ◽  
G A Kamp ◽  
R J Odink ◽  
S M P F de Muinck Keizer-Schrama ◽  
H A Delemarre-van de Waal ◽  
...  
Keyword(s):  
Short Stature ◽  
Adult Height ◽  
Treated Group ◽  
Idiopathic Short Stature ◽  
High Dose ◽  
Bone Maturation ◽  
Gh Treatment ◽  
Height Gain ◽  
Design And Methods ◽  
And Control

ObjectiveTo assess the long-term effect of prepubertal high-dose GH treatment on growth in children with idiopathic short stature (ISS).Design and methodsForty children with no signs of puberty, age at start 4–8 years (girls) or 4–10 years (boys), height SDS <−2.0 SDS, and birth length >−2.0 SDS, were randomly allocated to receive GH at a dose of 2 mg/m2 per day (equivalent to 75 μg/kg per day at start and 64 μg/kg per day at stop) until the onset of puberty for at least 2 years (preceded by two 3-month periods of treatment with low or intermediate doses of GH separated by two washout periods of 3 months) or no treatment. In 28 cases, adult height (AH) was assessed at a mean (s.d.) age of 20.4 (2.3) years.ResultsGH-treated children (mean treatment period on high-dose GH 2.3 years (range 1.2–5.0 years)) showed an increased mean height SDS at discontinuation of the treatment compared with the controls (−1.3 (0.8) SDS versus −2.6 (0.8) SDS respectively). However, bone maturation was significantly accelerated in the GH-treated group compared with the controls (1.6 (0.4) versus 1.0 (0.2) years per year, respectively), and pubertal onset tended to advance. After an untreated interval of 3–12 years, AH was −2.1 (0.7) and −1.9 (0.6) in the GH-treated and control groups respectively. Age was a positive predictor of adult height gain.ConclusionHigh-dose GH treatment restricted to the prepubertal period in young ISS children augments height gain during treatment, but accelerates bone maturation, resulting in a similar adult height compared with the untreated controls.

Idiopathic Short Stature

2001 ◽  
Vol 14 (s2) ◽  
Author(s):  
A.M. Pasquino ◽  
A. Albanese ◽  
M. Bozzola ◽  
G.E. Butler ◽  
F. Buzi ◽  
...  
Keyword(s):  
Short Stature ◽  
Adult Height ◽  
Idiopathic Short Stature ◽  
Psychological Benefits ◽  
Normal Children ◽  
Gh Treatment ◽  
Number Of Children ◽  
The Status ◽  
Gonadotrophin Releasing Hormone

AbstractIdiopathic short stature (ISS) is a term used to describe the status of children with short stature that cannot be attributed to a specific cause. Many children diagnosed as having ISS have partial GH insensitivity, which can result from disturbances at various points of the GH-IGF-I axis. Several clinical studies on spontaneous growth in ISS showed that adult height was almost in the range of target height. GH treatment led to adult height not significantly higher than the pretreatment predicted adult height in most reports. No metabolic side effects have been observed, even when the dose was higher than in GH deficiency. Manipulation of puberty with gonadotrophin releasing hormone analogues reported by a few authors in a small number of children has shown conflicting results. Long-term psychological benefits of GH therapy for short normal children have not been demonstrated to date.

scholarly journals Clinical and Molecular Evaluation of SHOX/PAR1 Duplications in Léri-Weill Dyschondrosteosis (LWD) and Idiopathic Short Stature (ISS)

2011 ◽  
Vol 96 (2) ◽  
pp. E404-E412 ◽  
Author(s):  
S. Benito-Sanz ◽  
E. Barroso ◽  
D. Heine-Suñer ◽  
A. Hisado-Oliva ◽  
V. Romanelli ◽  
...  
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Copy Number ◽  
Clinical Manifestations ◽  
Idiopathic Short Stature ◽  
Pseudoautosomal Region ◽  
Height Gain ◽  
Multiple Copies ◽  
Copy Number Changes ◽  
Design And Methods

abstract Context: Léri-Weill dyschondrosteosis (LWD) is a skeletal dysplasia characterized by disproportionate short stature and the Madelung deformity of the forearm. SHOX mutations and pseudoautosomal region 1 deletions encompassing SHOX or its enhancers have been identified in approximately 60% of LWD and approximately 15% of idiopathic short stature (ISS) individuals. Recently SHOX duplications have been described in LWD/ISS but also in individuals with other clinical manifestations, thus questioning their pathogenicity. Objective: The objective of the study was to investigate the pathogenicity of SHOX duplications in LWD and ISS. Design and Methods: Multiplex ligation-dependent probe amplification is routinely used in our unit to analyze for SHOX/pseudoautosomal region 1 copy number changes in LWD/ISS referrals. Quantitative PCR, microsatellite marker, and fluorescence in situ hybridization analysis were undertaken to confirm all identified duplications. Results: During the routine analysis of 122 LWD and 613 ISS referrals, a total of four complete and 10 partial SHOX duplications or multiple copy number (n &gt; 3) as well as one duplication of the SHOX 5′ flanking region were identified in nine LWD and six ISS cases. Partial SHOX duplications appeared to have a more deleterious effect on skeletal dysplasia and height gain than complete SHOX duplications. Importantly, no increase in SHOX copy number was identified in 340 individuals with normal stature or 104 overgrowth referrals. Conclusion: MLPA analysis of SHOX/PAR1 led to the identification of partial and complete SHOX duplications or multiple copies associated with LWD or ISS, suggesting that they may represent an additional class of mutations implicated in the molecular etiology of these clinical entities.

Height Gain and Safety Outcomes in Growth Hormone-Treated Children with Idiopathic Short Stature: Experience from a Prospective Observational Study

2019 ◽  
Vol 91 (4) ◽  
pp. 241-251 ◽  
Author(s):  
Christopher J. Child ◽  
Charmian A. Quigley ◽  
Gordon B. Cutler, Jr ◽  
Wayne V. Moore ◽  
Kupper A. Wintergerst ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
International Study ◽  
Study Data ◽  
Idiopathic Short Stature ◽  
Gh Treatment ◽  
Safety Issues ◽  
Safety Outcomes ◽  
Height Gain ◽  
Over Time

Background/Objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice. Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data. Results: Compared to children with isolated idiopathic GH deficiency (IGHD), those with ISS were shorter at baseline but had similar age and GH dose. Mean ± SD height SD score (SDS) increase was similar for ISS and IGHD, with 0.6 ± 0.3 (first), 0.4 ± 0.3 (second), 0.3 ± 0.3 (third), and 0.1 ± 0.3 (fourth year) for ISS. Girls with ISS (27% of subjects) were younger and shorter than boys but had similar height gain over time. At NAH in the ISS group (n = 467), mean ± SD age, GH duration, and height SDS were 17.3 ± 2.3 years, 4.6 ± 2.7 years, and –1.2 ± 0.9, respectively. Height gain from baseline was 1.1 ± 1.0 SDS and was greater for boys than girls (1.2 ± 1.0 vs. 0.9 ± 0.9), but boys were treated longer (5.1 ± 2.8 vs. 3.6 ± 2.5 years). Adverse events were reported for 24% with ISS versus 20% with IGHD – most were common childhood conditions or previously reported in GH-treated patients. Conclusions: GH-treated children with ISS achieved substantial height gain, similar to patients with IGHD. Fewer GH-treated girls were enrolled than boys, but with similar height SDS gain over time. No ISS-specific safety issues were identified. Thus, GH treatment of ISS appears to have a safety/effectiveness profile similar to that of IGHD.

scholarly journals Isolated Growth Hormone Deficiency and Idiopathic Short Stature: Comparative Efficiency after Growth Hormone Treatment up to Adult Height

2021 ◽  
Vol 10 (21) ◽  
pp. 4988
Author(s):  
Ana-Belen Ariza-Jimenez ◽  
Isabel Leiva Gea ◽  
Maria Jose Martinez-Aedo Ollero ◽  
Juan Pedro Lopez-Siguero
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Treatment ◽  
Treated Group ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Comparative Efficiency ◽  
Height Gain ◽  
Group A ◽  
Group B

Introduction: Treatment with growth hormone (GH) is not approved for idiopathic short stature (ISS) in Europe. Objectives: To compare the growth of children treated with isolated GH deficiency (IGHD) vs. ISS-treated and untreated children. Methods: A retrospective descriptive study of patients treated in the last 14 years for IGHD (Group A), in comparison with ISS-treated (Group B) and untreated (Group C) subjects. Results: Group A had 67 males, who showed a height gain of 1.24 SD. Group B had 30 boys, who showed a height gain of 1.47 SD. Group C had 42 boys, who showed an improvement of 0.37 SD. The final heights were −1.52 SD, −1.31 SD, and −2.03 SD, respectively. Group A and C did not reach their target heights (with differences of 0.27 SD and 0.59 SD, respectively). Group B surpassed their target height by 0.29 SD. Conclusions: The final heights of the IGHD and treated ISS are similar. Treated groups were taller than untreated groups.

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.

scholarly journals Management of children with idiopathic short stature

2006 ◽  
Vol 155 (suppl_1) ◽  
pp. S35-S38 ◽  
Author(s):  
Leo Dunkel
Keyword(s):  
Short Stature ◽  
Well Being ◽  
Idiopathic Short Stature ◽  
Controlled Study ◽  
Growth Disorders ◽  
Gh Treatment ◽  
Height Gain ◽  
Clinically Significant ◽  
Predicted Height ◽  
Dose Response Study

The Food and Drug Administration (FDA) approved the use of biosynthetic GH for the treatment of children with idiopathic short stature (ISS) in the US in 2003. Primarily, the decision was based on two studies: a randomized placebo-controlled study and a dose–response study, both demonstrating an increase in adult height over the predicted height at baseline and over placebo-treated controls by an average of 4–7 cm. Despite these data and FDA approval of GH treatment for ISS, there is still a significant controversy among paediatric endocrinologists about how, and to what extent, GH should be used in this indication. GH is clearly efficacious in several growth disorders and has the potential to alleviate debilitating short stature. However, it has been questioned whether ISS should be considered a condition warranting pharmacological treatment, whether the degree of morbidity of untreated ISS is clinically significant, and whether improved psychosocial status or well-being is achieved through GH treatment and height gain. The benefits must outweigh treatment costs and risks to justify GH treatment in ISS. The safety of GH treatment in ISS has been the main subject in two recent articles from pharmaceutical companies that conducted the pioneering studies mentioned earlier. No new safety concerns were observed in the ISS populations, but there were some limitations in study designs that prevent clinicians, their patients and families from ‘resting assured’. Studies addressing these controversial issues are needed before the widespread use of GH treatment in ISS is warranted.

scholarly journals The Effect of Gonadotropin-Releasing Hormone Analogue on Final Adult Height in Children with Idiopathic Short Stature

2019 ◽  
Vol 28 (6) ◽  
pp. 509-516 ◽  
Author(s):  
Nahla Khawaja ◽  
Hala Owaineh ◽  
Anwar Batieha ◽  
Oraib Frahid ◽  
Mohammed EL-Khateeb ◽  
...  
Keyword(s):  
Short Stature ◽  
Adult Height ◽  
Gonadotropin Releasing Hormone ◽  
Idiopathic Short Stature ◽  
Hormone Analogue ◽  
Historical Cohort ◽  
Releasing Hormone ◽  
Final Adult Height ◽  
Gonadotropin Releasing Hormone Analogue ◽  
Height Gain

Objective: To assess final adult height (FAH) in children with short stature treated with gonadotropin-releasing hormone analogue (GnRHa). Methods: All patients with idiopathic short stature (ISS) with normally timed puberty and a Tanner stage between 2 and 3, who achieved their FAH between 2005 and 2015, were included in this clinical historical cohort study. Height gain, FAH, and mid-parental height of 28 children with ISS who received GnRHa treatment for 1.8 ± 1.0 years to delay their puberty were compared to 31 untreated children. Results: The FAHs of the treated and the untreated girls were 151.3 ± 5.1 and 146.8 ± 3.8 cm (p = 0.01), respectively. The FAHs of the treated and the untreated boys were 156.4 ± 4.7 and 152.3 ± 5.7 cm (p = 0.111), respectively. The height gain in the treated and the untreated girls was 1.6 ± 7.8 and –3.6 ± 5.7 cm (p = 0.036), respectively. Height gain in the treated and the untreated boys was –5.1 ± 13.6 and –11.5 ± 8.4 cm (p = 0.171), respectively. Conclusion: GnRHa therapy has a modest effect in improving FAH in adolescent females with ISS but not in boys.

scholarly journals SAT-107 Improved Adult Height in Brazilian Turner Syndrome Patients Treated with Growth Hormone

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Renata Da Cunha Scalco ◽  
Adriana Farrant Braz ◽  
Alexsandra C Malaquias ◽  
Sonir Roberto Rauber Antonini ◽  
Gil Guerra-Junior ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Adult Height ◽  
Delayed Diagnosis ◽  
Bone Age ◽  
Treated Group ◽  
Gh Treatment ◽  
Significant Difference ◽  
Referral Hospitals ◽  
Height Gain

Abstract Background: Short stature is the most frequent clinical manifestation in Turner syndrome (TS), occurring in 98% of these patients. Growth hormone was shown to improve adult height in TS patients from diverse genetic backgrounds. However, there are few studies on adult height in TS patients from developing countries, where the diagnosis is frequently delayed. Objective: To compare adult height between GH-treated and untreated TS patients. Patients and methods: 120 GH-treated and 109 GH-untreated TS patients from 3 referral hospitals in Brazil were evaluated. The most common reasons for not treating TS patients with GH were late diagnosis or GH unavailability. Data on karyotype, parents’ height, puberty development and GH treatment were obtained from their medical records. Adult height was determined when growth velocity was inferior to 1cm/year during a minimum follow-up period of 12 months. Results: The frequency of 45,X karyotype was similar between the groups (48.7% vs. 41.9% in GH-treated vs. GH-untreated TS patients, respectively, P= 0.639). GH-treated TS patients started GH therapy at a chronological age (CA) of 11.2 ± 3.7 yr, bone age of 9.3 ± 3.1 yr, height SDS (British 1965 standards) -3.1 ± 1.1. GH mean dose was 48µg/kg.d and GH treatment duration was 5.4 ± 3.0 yr. Estrogen replacement was started late, at CA of 14.3 ± 2.0 yr in GH-treated and at 14.9 ± 1.9 yr in GH-untreated patients, and the rate of spontaneous puberty was similar between the groups (GH-treated 16.8% vs. GH-untreated 22,8%, P=0.304). Adult height was significantly higher after GH treatment (150.1 ± 5.8 cm vs. 143.3 ± 7.2 cm in GH-treated vs. untreated TS patients, respectively, P &lt; 0.001), even with a small but significant difference in target height between the groups (158.2 ± 4.8 vs. 159.8± 4.5 cm in GH-treated vs. untreated TS patients, respectively, P= 0.015). More than half of the TS GH-treated patients reached normal adult height (equal or higher than 150.2 cm), whereas only 15.6% of GH-untreated patients reached it. Conclusion: Despite the delayed diagnosis of TS patients in our cohort, GH treatment was associated with a significant height gain, and the TS GH-treated group was around 7 cm taller than the GH-untreated group.

The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis

2020 ◽  
Vol 33 (12) ◽  
pp. 1577-1588
Author(s):  
George Paltoglou ◽  
Ioannis Dimitropoulos ◽  
Georgia Kourlaba ◽  
Evangelia Charmandari
Keyword(s):  
Systematic Review ◽  
Growth Hormone ◽  
Short Stature ◽  
Human Growth Hormone ◽  
Adult Height ◽  
Linear Growth ◽  
Meta Analysis ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Idiopathic Short Stature

AbstractObjectivesIdiopathic short stature (ISS) is a recognized, albeit a controversial indication for treatment with recombinant human growth hormone (rhGH).The objective of the present study was to conduct a systematic review of the literature and meta-analyses of selected studies about the use of rhGH in children with ISS on linear growth and adult height (AH).MethodsA systematic literature search was conducted to identify relevant studies published till February 28, 2017 in the following databases: Medline (PubMed), Scopus and Cochrane Central Registry of Controlled Trials. After exclusion of duplicate studies, 3,609 studies were initially identified. Of those, 3,497 studies were excluded during the process of assessing the title and/or the abstract. The remaining 112 studies were evaluated further by assessing the full text; 21 of them fulfilled all the criteria in order to be included in the current meta-analysis.ResultsChildren who received rhGH had significantly higher height increment at the end of the first year, an effect that persisted in the second year of treatment and achieved significantly higher AH than the control group. The difference between the two groups was equal to 5.3 cm (95% CI: 3.4–7 cm) for male and 4.7 cm (95% CI: 3.1–6.3 cm) for female patients.ConclusionIn children with ISS, treatment with rhGH improves short-term linear growth and increases AH compared with control subjects. However, the final decision should be made on an individual basis, following detailed diagnostic evaluation and careful consideration of both risks and benefits of rhGH administration.

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