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 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.

The Role of Serial Sampling in the Diagnosis of Growth Hormone Deficiency

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 521-524
Author(s):  
Frank B. Diamond ◽  
E. Verena Jorgensen ◽  
Allen W. Root ◽  
Dorothy I. Shulman ◽  
Judy P. Sy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Growth Velocity ◽  
Idiopathic Short Stature ◽  
Study Cohort ◽  
Growth Study ◽  
Gh Treatment ◽  
Serial Sampling ◽  
The Mean ◽  
National Cooperative

We analyzed 12-hour serial sampling of growth hormone (GH) levels in two cohorts of short children: 96 children referred to a university endocrine clinic or studied on a research protocol and 825 children in the National Cooperative Growth Study of children treated with exogenous GH. The mean 12-hour GH levels correlated with growth velocity in 60 children with normal height and growth velocity in the university study, and this correlation was stronger in the boys. The testosterone levels also correlated with growth velocity and mean 12-hour GH levels in the boys. The mean 12-hour GH levels were lower in a group of 36 children with idiopathic short stature than in the control subjects, as were the peak GH levels within 1 hour after the onset of sleep and the insulin-like growth factor I levels. In the National Cooperative Growth Study cohort, pooled 12-hour GH levels were lower in the group with idiopathic GH deficiency (n = 300) than in the group with idiopathic short stature (n = 525), but the difference was not significant. The duration of GH treatment was the most significant predictor of change in the height SD score in both groups. Indices of spontaneous secretion of GH were not predictive of the response to GH treatment, nor were the results of provocative GH testing, the responses to GH treatment being similar in both groups over time. We conclude that the results of GH testing must be interpreted for each patient and that several testing modalities may be helpful in finding GH insufficiency that originates at various levels of the somatotropic axis.

scholarly journals SAT-105 The Natural History of Pituitary Cysts in Patients with Growth Hormone Deficiency and Idiopathic Short Stature

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zeyad El-Naghy ◽  
Nicholas Andrew Krasnow ◽  
James Haigney ◽  
Tara Patale ◽  
Liam McGuirk ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Pediatric Endocrinology ◽  
Post Contrast ◽  
Pituitary Cyst ◽  
Pituitary Cysts ◽  
Over Time

Abstract Background: The sequential follow-up of simple fluid-filled pituitary cysts (PC) has not been fully elucidated. In this study, we further report our follow up of PCs in a cohort of pediatric patients (PTs). Objective: To further analyze the sequential cyst volume (CV) change in short children. Patients and Methods: A pediatric endocrinology and neuroradiology center was queried for the presence of PCs. PTs who underwent multiple high resolution post-contrast MRIs (1mm slices) were subjects of this study. PTs with additional MRI abnormalities were excluded. Pituitary volumes (PV) and CVs were measured using the ellipsoid formula (LxWxH/2). The percentage of the gland occupied by the cyst (POGO) was measured and calculated. A cyst with a POGO ≤15% was defined as a small pituitary cyst (SPC), and a POGO >15% was defined as a large pituitary cyst (LPC). 34 PTs met inclusion criteria, all of whom were diagnosed with short stature (23 growth hormone deficient (GHD) PTs and 11 idiopathic short stature (ISS) PTs). All PTs were receiving GH during data collection. Results: The mean (MN) and median (MD) ages for these subjects were 10.7 yrs ±3.5 and 11.1 yrs, respectively (RSP). Of the 34 PTs, 24 PTs’ (71%) initial MRI demonstrated a SPC and 10 PTs’ (29%) initial MRI demonstrated a LPC. The MN and MD times between first and second MRIs were 1.23 yrs and 0.83 yrs RSP, with a range (RG) of 0.14 to 4.08 yrs. The MN and MD ΔCV for all PTs was 23.33% ±179.17% and -25.94% RSP, with a RG of -100.00% to 763.94%. The MN and MD ΔPOGO by the cyst for all PTs was 48.59% ±313.26% and -36.84% RSP, with a RG of -100.00% to 1734.79%. The MN and MD ΔCV for PTs with a SPC was 10.68% ±2.65% and 11.09% RSP, with a RG of -100.00% to 763.94%. The MN and MD ΔPOGO by the cyst for PTs with a SPC was 78.33% ±369.96% and -31.34% RSP, with a RG of -100.00% to 1734.79%. The MN and MD ΔCV for PTs with a LPC was -24.60% ±51.89% and -26.57% RSP, with a RG of -88.57% to 91.38%. The MN and MD ΔPOGO by the cyst for PTs with a LPC was -22.79% ±44.90% and -40.46% RSP, with a RG of -80.95% to 47.11%. Statistical analysis showed no significant %ΔCV or %ΔPOGO when comparing male vs. female, SPC vs. LPC, GHD vs. ISS, or pre-pubertal vs. pubertal PTs. Analysis of ΔPOGO of the 24 SPC PTs demonstrated that 4 (17%) of them developed into LPCs. Analysis of the 10 LPC PTs showed that 6 (60%) of them shrunk into SPCs, one of which re-enlarged into a LPC, and another of which fluctuated between LPC and SPC over a period of 7.34 yrs and 9 sequential MRIs. None of the PTs experienced significant sequelae related to their PCs. Conclusion: CV can change greatly over time, however few sequelae should be expected. LPCs tend to demonstrate major changes in size and should be tracked for CV change. A minority of SPCs will develop into LPCs. Prediction of change in CV over time requires more sequential data. Change in CV did not appear to be influenced by GH therapy.

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 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.

The Psychological Consequences of Turner Syndrome and Review of the National Cooperative Growth Study Psychological Substudy

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 488-491 ◽  
Author(s):  
Patricia T. Siegel ◽  
Richard Clopper ◽  
Brian Stabler
Keyword(s):  
Growth Hormone ◽  
Behavior Problems ◽  
Short Stature ◽  
Turner Syndrome ◽  
Child Behavior ◽  
Child Behavior Checklist ◽  
Idiopathic Short Stature ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Control Subjects

Objective. To present longitudinal data on the psychological profile of a cohort of girls with and without Turner syndrome (TS) treated for 3 years with growth hormone (GH). Methods. Among a sample of 283 children with short stature, 37 girls with TS were recruited at 27 US medical centers. Of the original cohort, 22 girls with TS, 13 girls with isolated growth hormone deficiency (GHD), and 12 girls with idiopathic short stature were followed through 3 years of GH therapy. All were school-age, were below the 3rd percentile for height, had low growth rates, and were naive to GH therapy. Psychological tests (the Wide Range Achievement Test and the Slosson Intelligence Test) were administered to the clinical groups within 24 hours of their first GH injection and yearly thereafter. Control subjects were 25 girls with normal stature matched for age and socioeconomic status, who were tested only at baseline. One parent of each subject also completed the Child Behavior Checklist for that subject. Results. At baseline, the clinical groups had more internalizing behavioral problems, had fewer friends, and participated in fewer activities than did the control subjects. The groups did not differ in mean IQ or academic achievement, but the TS group did have more problems in mathematics achievement. Height and growth rate significantly increased in the clinical groups over the 3 years of GH therapy, but IQ and achievement scores did not. Significant linear reductions were noted in both Internalizing and Externalizing Behavior Problems after GH treatment, with the TS group having fewer behavior problems before and after GH treatment than did the GHD–idiopathic short stature group. Decreases in specific Child Behavior Checklist subscales, including attention, social problems, and withdrawal, also were seen in the clinical groups after GH therapy. Conclusions. The comprehensive treatment of girls with TS should include educational and behavioral interventions in addition to traditional medical therapies.

scholarly journals The prevalence and volumetry of pituitary cysts in children with growth hormone deficiency and idiopathic short stature

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Nicholas Krasnow ◽  
Bradley Pogostin ◽  
James Haigney ◽  
Brittany Groh ◽  
Winston Weiler ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Growth Failure ◽  
Brain Magnetic Resonance Imaging ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Cyst Volume ◽  
Pituitary Cysts

AbstractBackgroundPituitary cysts have been speculated to cause endocrinopathies. We sought to describe the prevalence and volumetry of pituitary cysts in patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS).MethodsSix hundred and eighteen children evaluated for growth failure at the Division of Pediatric Endocrinology at New York Medical College between the years 2002 and 2012, who underwent GH stimulation testing and had a brain magnetic resonance imaging (MRI) prior to initiating GH treatment were randomly selected to be a part of this study. High resolution MRI was used to evaluate the pituitary gland for size and the presence of a cyst. Cyst prevalence, cyst volume and percentage of the gland occupied by the cyst (POGO) were documented.ResultsFifty-six patients had a cyst, giving an overall prevalence of 9.1%. The prevalence of cysts in GHD patients compared to ISS patients was not significant (13.5% vs. 5.7%, p=0.46). Mean cyst volume was greater in GHD patients than ISS patients (62.0 mm3vs. 29.4 mm3, p=0.01). POGO for GHD patients was significantly greater (p=0.003) than for ISS patients (15.3%±12.8 vs. 7.1%±8.0). Observers were blinded to patient groups.ConclusionsGHD patients had a significantly greater volume and POGO compared to ISS patients. This raises the question of whether cysts are implicated in the pathology of growth failure.

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.

Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?

2015 ◽  
Vol 28 (1-2) ◽  
Author(s):  
Tal Ben-Ari ◽  
Yael Lebenthal ◽  
Moshe Phillip ◽  
Liora Lazar
Keyword(s):  
Gender Differences ◽  
Growth Hormone ◽  
Short Stature ◽  
Standard Deviation Score ◽  
Idiopathic Short Stature ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Pubertal Status ◽  
Male Predominance ◽  
Predicted Height

AbstractGrowth hormone (GH) registries indicate that boys receive preferential GH treatment for idiopathic short stature (ISS). The aim was to determine whether age, auxological parameters, pubertal status, and target height differ between genders at GH initiation.Review of the computerized files of the endocrine department of a tertiary pediatric medical center identified 184 patients who started GH therapy for ISS between 2003–2011. Data on auxologic parameters, predicted height, parental height, and pubertal status were collected and compared between boys and girls.Boys accounted for a significantly higher percentage of the study group (65.8%, p<0.001). At onset of GH therapy, there were no significant differences between boys and girls in age (10.2±3.1 vs. 9.9±2.4 years), height-standard deviation score (SDS) (–2.64±0.5 vs. –2.79±0.5), body mass index-SDS[(–0.65±1.01) vs. (–0.80±1.13)], or pubertal status (66% vs. 63.5% prepubertal). Predicted height-SDS was significantly higher in boys (–1.95±1.05 vs. –2.56±0.73, p<0.001). Midparental height-SDS was similar in the two groups, as were paternal and maternal height.The similar age, height deficit, and pubertal status at onset of GH treatment in boys and girls suggests that gender differences do not exist. Male predominance may stem from family preferences to treat boys. Future studies are warranted to assess the psychosocial aspects in the decision to initiate therapy.

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