scholarly journals Histrelin Implantation and Growth Outcomes in Children With Congenital Adrenal Hyperplasia: An Institutional Experience

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Robert A Swendiman ◽  
Barbara E Coons ◽  
Craig A Alter ◽  
Vaneeta Bamba ◽  
Michael L Nance ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Precocious Puberty ◽  
Retrospective Cohort ◽  
Adult Height ◽  
Cohort Analysis ◽  
Bone Age ◽  
Adrenal Hyperplasia ◽  
Growth Data ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

Abstract Background Children with congenital adrenal hyperplasia (CAH) because of 21 hydroxylase deficiency (21OHD) are at risk for early or precocious puberty and a short adult height compared to population means and midparental height. The effect of histrelin in suppressing puberty and improving growth in these children has not been reported. Methods Retrospective cohort analysis of all patients (age ≤ 20) at our institution who underwent histrelin implantation between 2008 and 2017. Treated patients with CAH (classic and nonclassic forms of 21OHD) were identified and their growth data analyzed. Results Fifteen children with CAH were treated with histrelin for a median of 3 years (range 2–5; age at first implantation 7.7 ± 1.5 years). Bone age (BA) to chronologic age (CA) decreased from 1.57 ± 0.4 to 1.25 ± 0.25 (P < .01), while predicted adult height (PAH) increased by 7.1 ± 6.6 cm (P < .01). A subgroup of 10 children reached adult height. Similar changes in BA/CA and PAH were observed with therapy (P = .02). Adult height z improved compared to pretreatment PAH z (–1.42 ± 0.9 vs. –1.96 ± 1.1 respectively, P < .01), but remained lower than midparental height z (P = .01). Conclusion In this retrospective cohort study of children with CAH due to 21OHD and early or precocious puberty, histrelin implantation resulted in a decrease in BA progression compared to CA and an improvement in PAH. In the subgroup who completed growth, adult height remained significantly lower than midparental. These results need to be confirmed with prospective controlled studies.

Growth curves for congenital adrenal hyperplasia from a national retrospective cohort

2016 ◽  
Vol 29 (12) ◽  
Author(s):  
Patricia Bretones ◽  
Benjamin Riche ◽  
Emmanuel Pichot ◽  
Michel David ◽  
Pascal Roy ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adult Height ◽  
Bone Age ◽  
Strong Impact ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Bone Maturation ◽  
The Mean ◽  
Puberty Onset ◽  
21 Hydroxylase Deficiency

Abstract Background: In congenital adrenal hyperplasia (CAH), adjusting hydrocortisone dose during childhood avoids reduced adult height. However, there are currently no CAH-specific charts to monitor growth during treatment. Our objective was to elaborate growth reference charts and bone maturation data for CAH patients. Methods: We conducted a retrospective observational cohort study, in 34 French CAH centers. Patients were 496 children born 1970–1991 with genetically proven 21-hydroxylase deficiency. Their growth and bone maturation data were collected until age 18 together with adult height, puberty onset, parental height, and treatment. The mean (SD) heights were modeled from birth to adulthood. The median±1 SD and ±2 SDs model-generated curves were compared with the French references. A linear model for bone maturation and a logistic regression model for the probability of short adult height were built. Results: Growth charts were built by sex for salt wasting (SW) and simple virilizing (SV) children treated before 1 year of age. In girls and boys, growth was close to that of the general French population up to puberty onset. There was almost no pubertal spurt and the mean adult height was shorter than that of the general population in girls (−1.2 SD, 156.7 cm) and boys (−1.0 SD, 168.8 cm). Advanced bone age at 8 years had a strong impact on the risk of short adult height (OR: 4.5 per year advance). Conclusions: The 8-year bone age is a strong predictor of adult height. It will help monitoring the growth of CAH-affected children.

scholarly journals Delayed Diagnosis of Congenital Adrenal Hyperplasia with Salt Wasting Due to Type II 3β-Hydroxysteroid Dehydrogenase Deficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2076-2080 ◽  
Author(s):  
Trine H. Johannsen ◽  
Delphine Mallet ◽  
Harriet Dige-Petersen ◽  
Jørn Müller ◽  
Katharina M. Main ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Delayed Diagnosis ◽  
Bone Age ◽  
Hydroxysteroid Dehydrogenase ◽  
Type Ii ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency ◽  
Premature Pubarche

Abstract Classical 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3β-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17α-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3β-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly elevated Δ5-steroids, in particular 17α-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated Δ5-/Δ4-steroid ratios. Sequencing of the type II 3β-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17α-hydroxyprogesterone were found on blood spots from Guthrie’s test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3β-HSD gene. Because neonatal diagnosis could have prevented life-threatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology.

Growth of patients with congenital adrenal hyperplasia due to 21-hydroxylase in infancy, glucocorticoid requirement and the role of mineralocorticoid therapy

2018 ◽  
Vol 31 (9) ◽  
pp. 1019-1022
Author(s):  
Jack Sellick ◽  
Sarah Aldridge ◽  
Matthew Thomas ◽  
Tim Cheetham
Keyword(s):  
Standard Deviation ◽  
Congenital Adrenal Hyperplasia ◽  
Standard Deviation Score ◽  
Normal Growth ◽  
Height Velocity ◽  
Adrenal Hyperplasia ◽  
Growth Data ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

Abstract Background The dose of hydrocortisone therapy required to maintain normal growth in infants with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is lower than in later childhood. This reflects the presence of excess non-aromatisable rather than aromatisable androgen but there has been relatively little focus on the role of mineralocorticoid therapy. Methods Growth data of infants with CAH due to 21-hydroxylase deficiency (2008–2016) were reviewed and information regarding hydrocortisone and fludrocortisone regimen was collected. Change in height standard deviation (SD) and height velocity standard deviation score (SDS) were analysed during the first year of life. Results Growth data from 13 children (8 M) were analysed. Height (length) declined from a median of −0.69 SD at 3 months to −1.23 SD at 12 months with a reduction in height velocity SDS from 0.02 between 3 and 6 months to −2.22 between 9 and 12 months (p=0.017) despite a hydrocortisone dose at the lower end of the range as recommended in consensus guidelines. The glucocorticoid activity of hydrocortisone and fludrocortisone was negatively associated with growth velocity (r=−0.55; p=0.049) although renin activity was not suppressed. Conclusions Infants with 21-hydroxylase deficiency can be managed with replacement hydrocortisone. The reasons for this paradigm are now understood although our data confirm that the glucocorticoid activity of fludrocortisone needs to be taken into consideration as well.

scholarly journals Growth-Related Characteristics of Patients <18 Years of Age with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (21OHD): Real World Evidence from the I-CAH Registry

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A715-A716
Author(s):  
Mallory Farrar ◽  
Salma Rashid Ali ◽  
Jillian Bryce ◽  
Federico Baronio ◽  
Hedi L Claahsen-van der Grinten ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Children And Adolescents ◽  
Bone Age ◽  
World Health ◽  
Skeletal Maturation ◽  
Growth Chart ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Final Adult Height ◽  
21 Hydroxylase Deficiency

Abstract Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a rare, autosomal recessive disease of the adrenal cortex leading to a lack of cortisol production and compensatory ACTH secretion, which drives excess androgen production. The chronic exposure to excess androgen, coupled with supraphysiologic glucocorticoid doses, can lead to advanced skeletal maturation with reduced growth in puberty, premature epiphyseal closure, and shorter final adult height. The I-CAH Registry, launched in 2007, currently has &gt;1500 cases of CAH from 26 countries. Aim of the current study was to identify growth-related characteristics of children and adolescents with 21OHD CAH registered in the I-CAH registry and who were based in Europe. Methods: The I-CAH registry was queried on 8-Oct-2019 using the following criteria: CYP21A enzyme deficiency; European site, male or female, age &lt;18 years; and ≥1 growth-related assessment. Descriptive analyses were conducted using data from all patient visits, with age subgroups defined as follows: 0 to &lt;2 years (0-2yr), 2 to 11 years (2-11yr), and 12 to 17 years (12-17yr). Since I-CAH data are longitudinal, patients who aged during registry enrollment may be included in &gt;1 subgroup. Analyses included standard deviation scores (SDS) for patients’ height for chronological age (CA), weight for CA, and height for bone age (BA) using World Health Organization growth chart data for reference values. Results: Of 232 patients in 10 European countries, 126 (54%) were female and most were from Germany (25%), United Kingdom (23%), Netherlands (14%), and Italy (11%). The 232 patients had a total of 2042 visits, with 44% (900 visits) in the 0-2yr group, 42% (860 visits) in the 2-11yr group, and 14% (282 visits) in the 12-17yr group. No discernible pattern by age group was found for height for CA based on mean/median SDS scores. For weight for CA, mean/median SDS scores showed an increasing trend in older patients: 0-2yr (0.22/-0.06 [896 visits]); 2-11yr (0.47/0.55 [855 visits]); and 12-17yr (0.55/0.66 [278 visits]). Mean/median SDS scores for height for BA decreased with age: 0-2yr (0.31/0.05 [36 visits]); 2-11yr (-0.32/-0.23 [172 visits]); and 12-17yr (-0.49/-0.26 [44 visits]). Paired BA and CA values from 259 patient visits showed a trend towards bone age being greater than CA, starting at approximately 48 months of age and leveling out around 120-130 months. Mean BA was advanced by 9.7 months compared to CA (SD: 21.2 months, 95%; CI: 7.1 to 12.3 months, [p&lt;0.0001]). Conclusions: As previous research has indicated, I-CAH registry data suggest that children and adolescents with classic 21OHD CAH in Europe have advanced BA relative to CA, with height relative to BA tending to decrease with older age. The I-CAH registry offers the opportunity to study a variety of growth determinants and measurements with an option for subgroup analysis.

Executive functioning in children with congenital adrenal hyperplasia

2016 ◽  
Vol 65 (1) ◽  
pp. 49-52 ◽  
Author(s):  
A Monica Agoston ◽  
Maria Teresa Gonzalez-Bolanos ◽  
Margaret Semrud-Clikeman ◽  
Nancy Vanderburg ◽  
Kyriakie Sarafoglou
Keyword(s):  
Sex Differences ◽  
Executive Functioning ◽  
Congenital Adrenal Hyperplasia ◽  
Bone Age ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Estrogen Exposure ◽  
Androgen Exposure ◽  
21 Hydroxylase Deficiency ◽  
The Impact

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder characterized by impaired cortisol synthesis leading to excessive production of adrenal androgens. Prenatal and postnatal exposure to excess androgens may increase neural vulnerability to insult and affect cognitive functions, particularly dopamine-dependent neural circuits responsible for executive functioning (EF). Our study aimed to investigate relationship between more pronounced androgen exposure and EF-related behaviors in children with CAH, as well as sex differences in these associations. Parents of patients with CAH (n=41, boys=17, girls=24; age: M=8.41, SD=4.43) completed the Behavior Rating Inventory of Executive Function (BRIEF), a measure assessing behavioral manifestations of EF. Assessments of bone age advancement, a proxy of cumulative androgen exposure, were analyzed. Advanced bone age predicted more inhibition difficulties in boys but not in girls, and more difficulties in all other BRIEF domains in the total sample. Excessive androgen production affected EF such that more advanced bone age led to more EF-related difficulties. Sex differences in inhibition may result from estrogen exposure moderating the impact of androgens in girls but not in boys. Future interventions may include targeting EF in patients with CAH to enhance quality of life and reduce cognitive consequences associated with this disease.

scholarly journals Characteristics of growth in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency during adrenarche and beyond

2021 ◽  
Author(s):  
Tobias Troger ◽  
Grit Sommer ◽  
Mariarosaria Lang-Muritano ◽  
Daniel Konrad ◽  
Beatrice Kuhlmann ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adult Height ◽  
Final Height ◽  
Bone Age ◽  
Growth Patterns ◽  
Adrenal Hyperplasia ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency ◽  
The Impact

Abstract Context Patients with classic congenital adrenal hyperplasia (CAH) often fail to achieve their full growth potential. Adrenarche may accelerate bone maturation and thereby result in decreased growth in CAH. Objective To analyze the impact of growth during adrenarche on final height of adequately treated classic CAH patients. Design Retrospective, multi-center study. Setting Four academic pediatric endocrinology centers. Participants Fourty-one patients with classical CAH, born between 1990 and 2012. Main outcome measures We assessed skeletal maturation (bone age), growth velocity and (projected) adult height outcomes, and analyzed potential influencing factors, such as sex, genotype, and glucocorticoid therapy. Results Patients with classic CAH were shorter than peers (-0.4SDS±0.8SD) and their parents (corrected final height -0.6SDS±1.0SD). Analysis of growth during adrenarche revealed two different growth patterns: patients with accelerating bone age (49%), and patients with non-accelerating bone age compared to chronological age (BA-CA). Patients with accelerating BA-CA were taller than the normal population during adrenarche years (p=0.001) and were predicted to achieve a lower adult height SDS (-0.9SDS, 95%CI -1.3;-0.5) than non-accelerating patients when assessed during adrenarche (0.2SDS, 95%CI -0.3;0.8). Final adult height was similarly reduced in both accelerating and non-accelerating BA-CA groups (-0.4SDS, 95%CI -0.9;0.1 vs -0.3SDS, 95%CI -0.8;0.1). Conclusions Patients with and without significant bone age advancement, and thus differing height prediction during adrenarche, showed similar (predicted) final height when reassessed during pubertal years. Bone age alone should not be used during adrenarche as clinical marker for metabolic control in CAH treatment.

Sign in / Sign up

Export Citation Format

Share Document