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 Growth Hormone Stimulation Testing Patterns Contribute to Gender Disparities in Growth Hormone Treatment

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A677-A677
Author(s):  
Camilia Kamoun ◽  
Colin Patrick Hawkes ◽  
Hareesh Gunturi ◽  
Andrew Nahum Dauber ◽  
Joel N Hirschhorn ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Statistical Significance ◽  
Gender Disparities ◽  
Categorical Variables ◽  
P Value ◽  
Z Score ◽  
Gh Treatment ◽  
Poor Growth ◽  
Entire Study

Abstract Introduction: Growth hormone (GH) registries demonstrate that males outnumber females 2:1 for all indications combined and 3:1 for the idiopathic short stature indication. The aim of this study was to determine if gender disparities in GH treatment are due to differences in rates of stimulation testing and/or GH prescribing. Methods: Retrospective chart review was performed including children aged 2-16 years seen for short stature or poor growth in 2012-2019 at a large tertiary referral center. Children previously diagnosed with GHD were excluded. Continuous variables, reported as medians [IQR], were compared by Wilcoxon rank sum test and categorical variables by Chi-squared test. A two-tailed p-value &lt;0.05 defined statistical significance. Results: Of 10,125 children seen for evaluation of short stature or poor growth (35% [3542] females [F], 65% [6583] males [M]), 1,245 underwent GH stimulation testing (30% [379] F, 70% [866] M). A larger proportion of males than females were tested (M 13.2%, F 10.7%; p &lt;0.001). Amongst the entire study population, females had lower height Z-scores than males (F -1.98 [-2.46, -1.44], M -1.80 [-2.24, -1.31]; p&lt;0.001). This difference persisted in those who proceeded to GH stimulation testing (F -2.52 [-3.00, -2.04], M -2.18 [-2.6, -1.81]; p&lt;0.001) and GH treatment (F -2.62 [-3.11, -2.07], M -2.19 [-2.60, -1.81; p&lt;0.001). Mean difference between height Z-score and mid-parental height (MPH) Z-score for the entire population did not differ by sex (F -1.52 [-2.17, -0.87], M -1.52 [-2.04, -0.97]; p=0.76), but the difference was greater in females among those who underwent GH stimulation testing (F -1.95 [-2.57, -1.40], M -1.79 [-2.32, -1.32]; p=0.009) and started GH treatment (F -1.93 [-2.58, -1.48], M -1.80 [-2.30, -1.32]; p=0.016). Peak stimulated GH levels were similar for males and females (F 9.6 [6.0, 13.6] ng/mL, M 9.4 [6.1, 13.2] ng/mL, p=0.62). The proportion of children prescribed GH after stimulation testing did not differ by gender (F 55% [208], M 56% [488]; p=0.63). This finding did not change upon sub-analysis by peak stimulated GH concentration groups (peak GH concentrations &lt;7 ng/mL, 7-10 ng/mL, and &gt;10 ng/mL). Conclusion: The male predominance among children seen for subspecialist evaluation of short stature was compounded by a greater proportion of those males subsequently undergoing GH stimulation testing despite less severe short stature. Although females who underwent GH stimulation testing had greater height deficit from their genetic potential than tested males, peak stimulated GH concentrations and GH prescription rates were similar by sex. Thus, gender disparities in GH treatment occur at the subspecialist referral and stimulation testing, but not GH prescription, steps. Further, GH stimulation test results failed to account for the more severe shortness among tested females, yet another limitation identified with such testing.

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.

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 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.

Correlation Between the Responses to Growth Hormone (GH) Treatment During Childhood and Adulthood in a Monocentric Cohort of GH-Deficient Patients

2018 ◽  
Vol 50 (06) ◽  
pp. 462-468
Author(s):  
Sarah Thilmany ◽  
Leila Mchirgui ◽  
Chloé Brunelle ◽  
Véronique Beauloye ◽  
Dominique Maiter ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Velocity ◽  
Significant Positive Correlation ◽  
Growth Parameters ◽  
Hormone Deficiency ◽  
First Year ◽  
Z Score ◽  
Gh Treatment ◽  
Positive Correlation ◽  
Igf I

AbstractOur aim was to analyze a cohort of patients with childhood-onset growth hormone deficiency (GHD) to evaluate if there is some correlation between the response to GH treatment during childhood and adulthood, respectively. This was an observational retrospective monocentric cohort study of 47 patients treated with GH during childhood and adulthood. Changes in growth parameters during childhood were compared with the increase of IGF-I z-score and other indexes of GH response (body composition, lipid profile) after 1 year of treatment in adulthood. The only significant positive correlation was observed between final growth velocity during the last year of childhood GH treatment and increase in IGF-I z-score in GH-treated adults (r=0.592, p=< 0.01). No correlation was observed between growth-promoting effects of GH as child and metabolic changes induced by GH as adult. We also observed a negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults (r=− 0.335, p <0.05). No significant positive correlation could be observed between the main parameters that evaluate response to GH treatment in children and adults. However, the final growth velocity, which may be considered as one of the main criteria of end of GH treatment in children, was identified as parameter that could predict future response to GH treatment in adulthood.

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.

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 Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jung-Eun Moon ◽  
Cheol Woo Ko
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Human Growth ◽  
Bone Age ◽  
Pediatric Endocrinology ◽  
Gh Therapy ◽  
Gh Treatment ◽  
The Impact

Purpose. Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well. Objective. To investigate the effects of GH therapy in SGA patients with short stature according to BA delay. Methods. We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children’s Hospital. Results. Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82; p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65; p=0.002). When height SDS was compared between with and without GHD, there were no significant differences. Conclusions. Delayed BA (>2 years) may impact the response to GH treatment in SGA children with 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.

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