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.

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.

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.

scholarly journals No Evidence for a Difference in 2D:4D Ratio between Youth with Elevated Prenatal Androgen Exposure due to Congenital Adrenal Hyperplasia and Controls

2020 ◽  
Author(s):  
Gideon Nave ◽  
Christina M. Koppin ◽  
Dylan Manfredi ◽  
Gareth Richards ◽  
Steven J. Watson ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Large Body ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Left Hand ◽  
Androgen Exposure ◽  
Wide Range ◽  
Prenatal Androgen Exposure ◽  
21 Hydroxylase Deficiency ◽  
Prenatal Androgen

AbstractThe second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: □ = -0.001 (−0.008, 0.006)]; females: □ = -0.004 [-0.015, 0.007]; males: □ = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

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 &lt; .01), while predicted adult height (PAH) increased by 7.1 ± 6.6 cm (P &lt; .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 &lt; .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.

scholarly journals Effects of Pre and Post-Natal Androgen Exposure on Psychosexual Aspects and Gender Change in Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A500-A501
Author(s):  
Rafael Loch Batista ◽  
Marlene Inacio ◽  
Mirela Costa de Miranda ◽  
Guiomar Madureira ◽  
Larissa Garcia Gomes ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Male Gender ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Androgen Exposure ◽  
Sex Assignment ◽  
And Gender ◽  
21 Hydroxylase Deficiency ◽  
Gender Change

Abstract Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up 90% of CAH. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess in both salt-wasting (SW) or simple virilizing (SV) forms. As androgens play a role in the human psychosexual development favoring male psychosexuality, this study was designed to evaluate the impact of androgen exposure on the psychosexuality of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort includes 46,XX individuals (115 female-assigned; 8 male-assigned) with a molecular diagnosis of CAH due to CYP21A2 pathogenic variants in homozygous or compounds heterozygous state. External genitalia virilization was scored using Prader scale. Phenotype, time at diagnosis, sex assignment, and gender change were assessed. The gender role at childhood was assessed through the playmates and toys profile at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report sexual identity. Compliance of glucocorticoid replacement was assessed by adequate testosterone and androstenedione serum levels for age. Results: CAH was diagnosed at the neonatal time in 73% (n=78). Fifth-nine (51%) had the SW form and 49% (n=56) had the SV form. While all cases of SW were diagnosed at the neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (p=&lt;.001). The median of Prader score was 3 in both forms. Male sex assignment was associated with more virilized external genitalia (p=.002). Gender change occurred in 6 cases (female to male), all with SV form. The prader score was higher among those who changed gender (p=.01). All of those who changed their gender had poor treatment compliance. A total of 13% (n=15) of all groups defined themselves as homosexual. There was a strong association between male toys and preference for male playmates in childhood with homosexuality and male gender identity in adulthood with both gender change from female to male and homosexuality. Conclusion: Prenatal androgen exposure favors male psychosexuality in 46,XX CAH individuals as observed by the association between highest Prader scores and all assessed psychosexual outcomes. This influence is also substantiated by post-natal androgen exposure as observed by compliance issues and late diagnosis among those who changed from female to male gender.

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.

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