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.

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 Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

2016 ◽  
Vol 174 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Brigitte Odenwald ◽  
Uta Nennstiel-Ratzel ◽  
Helmuth-Günther Dörr ◽  
Heinrich Schmidt ◽  
Manfred Wildner ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hospital Admissions ◽  
Discharge Summary ◽  
Severe Illness ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency

ObjectiveTo evaluate adrenal crises after the start of treatment up to the age of 6 years in children with classic congenital adrenal hyperplasia (CAH).DesignAnalysis of data extracted from a population-based prospective long-term follow-up study of children detected in neonatal screening.MethodsData of 102 Bavarian children with classic CAH due to 21-hydroxylase deficiency were analyzed, using parental questionnaires and medical reports. Parent-reported hospital admissions of children diagnosed with acute health impairment were included in the analysis if salt loss (hyponatremia) or hypoglycemia was documented in the discharge summary.ResultsA total of 74 children (72.5%) had no report of hospital admissions with salt loss or hypoglycemia during the observational period. However, in 27.5% of the children, 22 salt-wasting crises (seven of these also with low blood glucose) and 16 hypoglycemic episodes without salt loss were reported. Furthermore, the cumulative incidence for seizures was elevated; 13 children experienced seizures during hyponatremia or hypoglycemia. Most adrenal crises were triggered by infections, often with inappropriate emergency management, but in 11 cases hypoglycemia occurred unexpectedly, without evidence of severe illness and without any management errors. Frequency of adrenal crises was 6.5 per 100 patient years (95% CI: 4.6–8.8).ConclusionsCrisis prevention remains a permanent challenge for families and physicians caring for children with classic CAH. Expert care and compliance with emergency recommendations are crucial. Further research on the interactions among glucocorticoid deficiency, adrenomedullary dysfunction, and glucose metabolism is necessary for the prevention of hypoglycemia, especially in young CAH patients.

Growth Patterns and Final Height in Congenital Adrenal Hyperplasia due to Classical 21-Hydroxylase Deficiency

2001 ◽  
Vol 55 (4) ◽  
pp. 161-171 ◽  
Author(s):  
Gábor Hargitai ◽  
János Sólyom ◽  
Tadej Battelino ◽  
Jan Lebl ◽  
Zuzanna Pribilincová ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Final Height ◽  
Growth Patterns ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

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.

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 MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment

2017 ◽  
Vol 176 (4) ◽  
pp. R167-R181 ◽  
Author(s):  
Anne Bachelot ◽  
Virginie Grouthier ◽  
Carine Courtillot ◽  
Jérôme Dulon ◽  
Philippe Touraine
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Management Strategies ◽  
The United States ◽  
Fertility Treatment ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency ◽  
And Control

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge.

scholarly journals OR25-02 A Phase 3 Study of a Modified-Release Hydrocortisone in the Treatment of Congenital Adrenal Hyperplasia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Deborah P Merke ◽  
Ashwini Mallappa ◽  
Wiebke Arlt ◽  
Aude Brac de la Perriere ◽  
Angelica Linden Hirschberg ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Disease Control ◽  
Hormonal Control ◽  
Dose Titration ◽  
Modified Release ◽  
Adrenal Hyperplasia ◽  
Diurnal Cortisol ◽  
Classic Cah ◽  
The Mean ◽  
21 Hydroxylase Deficiency

Abstract Background: Patients with congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency have poor health outcomes related to inadequate glucocorticoid (GC) replacement. We compared disease control of adults with classic CAH treated with a modified release hydrocortisone (MRHC), which replicates physiological diurnal cortisol secretion, versus standard GC therapy. Methods: 6 month, open label, study in 122 patients randomised either to treatment with MRHC (Chronocort®, Diurnal Ltd, Cardiff, UK) twice daily at ~ 0700h & ~2300h, or to remain on their standard GC regimen (hydrocortisone, prednisolone, prednisone, dexamethasone). Patients had 24-hr profiling of serum 17-hydroxyprogesterone (17-OHP) at baseline and for dose titration at 4 and 12 weeks. The primary efficacy endpoint was the change from baseline to 24 weeks in the natural logarithm of the mean of the 24-hr standard deviation score (SDS) profile for 17-OHP. Results: Both groups achieved improved hormonal control at 24 weeks. The mean 24-hour 17-OHP SDS was significantly lower on MRHC compared to standard GC at 4 weeks (p = 0.0074) and 12 weeks (p = 0.019), but not at 24 weeks. In post-hoc analyses at 24 weeks, MRHC treatment showed a greater reduction in 17-OHP SDS compared to standard GC in the morning, 0700-1500h (p = 0.0442) and a greater reduction in log transformed 17-OHP 24 hour AUC (p=0.0251). Defining a morning 17-OHP <1200ng/dl (<36 nmol/L) as good control, for patients not controlled at baseline 85% were well controlled at 24 weeks with MHRC versus 50% on standard GC. For patients controlled at baseline 100% were controlled at 24 weeks on MHRC versus 84% with standard GC (p = 0.0018). The variability of 17-OHP over 24 hours was significantly reduced in the MRHC group compared to standard GC: the ratio of amplitude at 24 weeks divided by amplitude at baseline was for MRHC, 0.361 [95% CI: 0.235, 0.651], and standard GC, 0.917 [0.773, 1.366]; (p = 0.0001).There were no adrenal crises on MRHC and fewer stress doses despite similar incidence of inter-current illness to the standard GC group which had 3 adrenal crises. MRHC was associated with patient reported benefit including restoration of menstruation in 4 patients on MRHC and 1 on standard GC and two partner pregnancies in patients on MRHC and none on standard GC. Discussion: This is the largest randomised controlled trial of GC treatment in CAH and showed that intensification of therapy could improve control of the androgen-precursor, 17-OHP, and that this hormonal control was superior in the morning with MRHC. MRHC reduced the fluctuations in 17-OHP such that in the majority of patients the 17-OHP profile was within the reference range throughout 24 hours, providing consistent and optimal disease control. Conclusion: Diurnal cortisol replacement with a MRHC improves the biochemical control of classic CAH with a twice-daily therapeutic regimen.

Near-final height in 82 Chinese patients with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency: a single-center study from China

2016 ◽  
Vol 29 (7) ◽  
Author(s):  
Lin Juan ◽  
Ma Huamei ◽  
Su Zhe ◽  
Li Yanhong ◽  
Chen Hongshan ◽  
...  
Keyword(s):  
Treatment Group ◽  
Congenital Adrenal Hyperplasia ◽  
Early Treatment ◽  
Final Height ◽  
Adrenal Hyperplasia ◽  
Target Height ◽  
Hydroxylase Deficiency ◽  
Cox Regression Analysis ◽  
Late Treatment ◽  
21 Hydroxylase Deficiency

AbstractThe objective of this study was to identify variables that might interfere with reaching the near final height (NFH) in Congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD).A cross-sectional study of 82 (24 males and 58 females) classic (23 salt-wasting form [SW] and 59 simple-virilizing form [SV]) CAH 21-OHD patients seen in our institution between 1989 and 2015 with 10.6 (0.5~25.5) years of follow-up who reached their NFH was conducted. The variables related to NFH were explored.NFH (153.35±8.31) cm, (–1.9±1.1) SD was significantly lower than the normal population (p<0.001). The treated patients reached a significantly higher NFH (–1.7±1.1) SD than those untreated (–2.6±1.0) SD (p<0.05). Both of early treatment and late treatment group were taller than untreated group (p<0.001, p=0.013, respectively), and early treatment group had a taller height trend than late treatment group (p=0.089). A better height outcome was observed in patients with advantage in target height, good compliance, and low hydrocortisone dose by multivariate Cox regression analysis in 62 treatment patients. NFH and hydrocortisone dose was negatively correlated (r=–0.23, p=0.078) in treated group. Patients complicated by central precocious puberty (CPP) received gonadotropin-releasing hormone analogue (GnRHa) plus letrozole had increased NFH with height SD for bone age and Ht SD improved after treatment compare to no intervention group (p=0.001, p=0.035).Patients with classic 21-OHD have blunted final height, as compared with their target height and the population norm, not-treated even worse. Careful treatment adjustments have a favorable influence on growth. Alternative treatments, such as the use of puberty inhibitors GnRHa in addition to anti-estrogen therapy letrozole can somewhat improve NFH in children with 21-OHD complicated by CPP.

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