scholarly journals Racial/Ethnic Disparities in US Pediatric Growth Hormone Treatment

2018 ◽  
Vol 90 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Adda Grimberg ◽  
Anders Lindberg ◽  
Michael Wajnrajch ◽  
Andrew J. Cucchiara ◽  
Cecilia Camacho-Hübner
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Census Data ◽  
Treatment Initiation ◽  
Ethnic Disparities ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Male Predominance ◽  
Relative Risks ◽  
Racial Ethnic

Background/Aims: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. Methods: Race/ethnicity-based expected frequencies of height <–2.25 SD were determined by applying relative risks for short stature, calculated from a regional population of 189,280 pediatric primary care patients, to US census data, and compared to racial/ethnic proportions of US subjects enrolled in the Pfizer International Growth Study (KIGS) using the χ2 test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). Results: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (–2.97 vs. –2.56 SD) and to their mid-parental heights (–2.47 vs. –1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (–0.86 vs. –0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (–1.12 vs. –0.08 SD). Male predominance did not differ by race for any or all indications. Conclusion: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.

Growth hormone stimulation testing patterns contribute to sex differences in pediatric growth hormone treatment

2021 ◽  
Author(s):  
Camilia Kamoun ◽  
Colin Patrick Hawkes ◽  
Hareesh Gunturi ◽  
Andrew Dauber ◽  
Joel N. Hirschhorn ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Sex Differences ◽  
Short Stature ◽  
The United States ◽  
Medical Decision ◽  
Z Score ◽  
Growth Data ◽  
Gh Treatment ◽  
Poor Growth ◽  
Male Predominance

Introduction: Males are twice as likely as females to receive pediatric growth hormone (GH) treatment in the United States, despite similar distributions of height z-scores in both sexes. Male predominance in evaluation and subspecialty referral for short stature contributes to this observation. This study investigates whether sex differences in GH stimulation testing and subsequent GH prescription further contribute to male predominance in GH treatment. Methods: Retrospective chart review was conducted of all individuals, age 2-16 years, evaluated for short stature or poor growth at a single large tertiary referral center between 2012-2019. Multiple logistic regression models were constructed to analyze sex differences. Results: Of 10,125 children referred for evaluation, a smaller proportion were female (35%). More males (13.1%) than females (10.6%) underwent GH stimulation testing (p<0.001) and did so at heights closer to average (median height z-score -2.2 [interquartile range (IQR) -2.6, -1.8] vs. -2.5 [IQR -3.0,-2.0], respectively; p<0.001). The proportion of GH prescriptions by sex was similar by stimulated peak GH level. Predictor variables in regression modeling differed by sex: commercial insurance predicted GH stimulation testing and GH prescription for males only, whereas lower height z-score predicted GH prescription for females only. Conclusions: Sex differences in rates of GH stimulation testing, but not subsequent GH prescription based on response to GH stimulation testing, seem to contribute to male predominance in pediatric GH treatment. That height z-score predicted GH prescription in females but not males raises questions about the extent to which sex bias—from children, parents and/or physicians—, as opposed to objective growth data, influence medical decision-making in the evaluation and treatment of short stature.

scholarly journals ACAN Gene Mutations in Short Children Born SGA and Response to Growth Hormone Treatment

2016 ◽  
Vol 102 (5) ◽  
pp. 1458-1467 ◽  
Author(s):  
Manouk van der Steen ◽  
Rolph Pfundt ◽  
Stephan J.W.H. Maas ◽  
Willie M. Bakker-van Waarde ◽  
Roelof J. Odink ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Bone Age ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Midface Hypoplasia ◽  
Short Children ◽  
Hormone Analog

Abstract Background: Some children born small for gestational age (SGA) show advanced bone age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations have been described in children with short stature and advanced BA. Objective: To determine the presence of ACAN gene mutations in short SGA children with advanced BA and assess the response to GH treatment. Methods: BA assessment in 290 GH-treated SGA children. ACAN sequencing in 29 children with advanced BA ≥0.5 years compared with calendar age. Results: Four of 29 SGA children with advanced BA had an ACAN gene mutation (13.8%). Mutations were related to additional characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and broad great toes (P = 0.003). Children with one or fewer additional characteristic had no mutation. Of children with two additional characteristics, 50% had a mutation. Of children with three additional characteristics, 100% had a mutation. All GH-treated children with a mutation received gonadotropin-releasing hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than his father with the same ACAN gene mutation. Conclusion: This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have an ACAN gene mutation. ACAN sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems, or broad great toes. Our findings suggest that children with an ACAN gene mutation benefit from GH treatment with 2 years of GnRHa.

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 First report on growth hormone treatment response in a patient with spondylodysplastic type of Ehlers-Danlos syndrome with normal growth hormone secretion

2021 ◽  
Vol 50 (1) ◽  
pp. 47-56
Author(s):  
Katarina Božić ◽  
Tatjana Milenković ◽  
Srđan Pašić ◽  
Katarina Mitrović ◽  
Slađana Todorović ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Case Report ◽  
Short Stature ◽  
Treatment Response ◽  
Growth Hormone Treatment ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Ehlers Danlos Syndrome ◽  
Gh Secretion ◽  
First Case

Introduction/Aim: Spondylodysplastic Ehlers-Danlos Syndrome (sdEDS) is a rare genetic disorder of collagen synthesis, caused by a mutation in the B4GALT7, B3GALT6, or SLC39A13 gene. Features of this very rare disorder are short stature, hypotonia, hyperflexible joints, soft, thin, and overly stretchable skin, sparse hair and eyebrows, elderly face, wide forehead and prolonged wound healing. Molecular genetic analysis is needed for definite confirmation of the diagnosis. So far, only three case reports describing growth hormone treatment response in patients with sdEDS have been published. All of these patients had growth hormone (GH) deficiency. We present the first case report regarding growth hormone treatment response in a patient with sdEDS and normal GH secretion (without GH deficiency). Case report: Patient was a girl with short stature and normal GH secretion. Having in mind that the girl was born small for the gestational age, due to her short stature, she started using HR, before the diagnosis of sdEDS was made. Based on the lack of improvement in growth velocity as well as the girl's phenotype, genetic analyses were performed and the diagnosis of sdEDS due to biallelic mutations of the B4GALT7 gene was established. After the diagnosis of sdEDS was made and due to suboptimal response in growth velocity to the GH treatment, the GH therapy was stopped at the age of 11 years. Conclusion: This is a first case report regarding GH treatment in a child with sdEDS and normal GH secretion, demonstrating a very limited therapeutic effect of GH on linear growth in the presented patient.

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.

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.

scholarly journals Growth Hormone Treatment in Children Born Small for Gestational Age (SGA)

PRILOZI ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 143-149
Author(s):  
Aleksandra Janchevska ◽  
Marina Krstevska-Konstantinova ◽  
Velibor Tasic ◽  
Zoran Gucev
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Short Stature ◽  
Growth Velocity ◽  
Growth Hormone Treatment ◽  
Hormone Treatment ◽  
Genetic Alterations ◽  
Gh Treatment ◽  
Exon 2 ◽  
Dysmorphic Features

Abstract Introduction: Growth failure is a common consequence in small for gestational age (SGA) children. Patients and Methods: The growth patterns and serum insulin like growth factor 1 (IGF1) concentrations before and after the 1st year under growth hormone treatment of 32 short stature SGA born children have been evaluated. In addition, we investigated the insulin like growth factor 1 receptor (IGF1R) exon 2 as a hotspot for IGF1R genetic alterations. It is of note that no dysmorphic features were observed in this group of children. Results: The tests for pituitary reserve were within normal ranges for all 32 patients. Growth hormone (GH) treatment (0.037 mg/kg/day) was initiated at the mean age of 9.32±3.19 years. Growth velocity increased yearly from −1.80 SDS after the first year to −0.03 SDS in the sixth year of treatment. Their IGF1 serum concentrations before treatment were age and sex appropriate, while during treatment a significant increase was observed fitting in the upper third of the normal range: before the treatment IGF1 SDS was 0.84±1.78 after 1st year the concentrations increased to IGF1 SDS 0.94±2.23. No genetic alterations were found in the IGF1R exon 2 by PCR analysis. Conclusions: Herein we present 32 short stature SGA children with no dysmorphic features treated with GH. They all had increased growth velocity and entered the normal growth range on their growth charts. No side-effects were observed. GH treatment in children with no genetic alterations on the IGF1R exon 2 is safe and efficient in treating SGA children with short stature.

scholarly journals Racial/Ethnic Disparities in the Investigation and Treatment of Pediatric Growth Hormone Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A688-A689
Author(s):  
Colin Patrick Hawkes ◽  
Hareesh Gunturi ◽  
Andrew Nahum Dauber ◽  
Joel N Hirschhorn ◽  
Adda Grimberg
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Ethnic Disparities ◽  
Retrospective Chart Review ◽  
The United States ◽  
Prescribing Patterns ◽  
Hormone Deficiency ◽  
Hispanic Children ◽  
Gh Treatment ◽  
Chi Squared

Abstract Introduction : In the United States, non-Hispanic white (NHW) children are disproportionately over-represented relative to children of racial and ethnic minorities in pediatric growth hormone (GH) treatment registries. This study sought to determine if this racial inequity is due to differences in GH stimulation testing and/or GH prescribing patterns in children referred for endocrine evaluation of short stature. Methods : Retrospective chart review was performed including children aged 2-16 years, with height z-score ≤ -1.5, and of NHW, non-Hispanic black (NHB) or Hispanic race/ethnicity, referred for endocrine growth evaluation between January 1, 2012 and December 31, 2019. Age, sex, anthropometry, GH stimulation test results and GH treatment data were extracted. Comparisons between NHB, NHW and Hispanic children were performed using analysis of variance, chi-squared tests, Mann Whitney U and logistic regression tests. Results : This study included 7,425 patients (5,905 NHW, 800 NHB, and 720 Hispanic). GH stimulation testing was performed in 992, and 576 were prescribed GH. NHW children were 1.4 (95% CI 1.04 - 1.8) times more likely than NHB children and 1.7 (95% CI 1.2 - 2.2) times more likely than Hispanic children to undergo GH stimulation testing. NHB children treated with GH had: 1) lower median peak GH concentration when compared with NHW (p=0.02) and Hispanic (p=0.08) children (NHB 4.7 [1.2, 8.3] ng/ml, NHW 7.2 [4.9, 9.7] ng/ml, Hispanic 7.1 [4.3, 11.9] ng/ml); 2) lower median height z-scores than NHW (p=0.01) but not Hispanic children (p=0.5); and 3) a greater height deficit from mid-parental height when compared with NHW (p=0.01) and Hispanic (p=0.002) children Discussion: Racial and ethnic disparities are present in the evaluation and treatment of children with disordered growth. This likely results from both over-investigation of NHW children as well as under-investigation and under-treatment of children from minority communities. The evaluation and treatment of children with short stature should be determined by clinical concern alone, but this is unfortunately not current practice.

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