Classical Classical Congenital Adrenal Hyperplasia Research Articles

Evaluation of aggression level in adolescent girls with classical congenital adrenal hyperplasia.

In patients with classical congenital adrenal hyperplasia (CAH), virilization affects the brain and external genitalia due to antenatal androgen exposure. There are few studies on how the effects of androgens on brain virilization are reflected in behavior. However, there is no study focused on the adolescence period. The aim of this study was to evaluate the level of aggression in adolescent girls with classical CAH (due to 21 hydroxylase and 11β hydroxylase deficiency) and to investigate the disease-related factors that may affect aggression. Twenty female and 20 male patients aged 13-20 years, diagnosed with classical CAH, with 21 hydroxylase deficiency and 11β hydroxylase deficiency, and 20 healthy girls and 20 boys from the same age group were included. The Buss-Perry Aggression Scale (BPAS), which consists of four subgroups measuring physical aggression, verbal aggression, hostility, and angry behaviors, was used. The ages of the male and female patients with CAH were 16.30 ± 2.65 and 16.60 ± 2.41 years, respectively. Total aggression scale scores were 73.3 ± 14.6 in adolescent girls with CAH, 74.1 ± 11.2 in healthy girls, 71.5 ± 14.8 in boys with CAH, and 75.3 ± 14.5 in healthy boys (p > .05). There was no difference between the subscale scores of patients and healthy adolescents. Aggression scores in adolescents with CAH increased significantly with age. In this study, we found no difference between the aggression scores of adolescents with classical CAH compared to their healthy peers. The total aggression score and subscale were similar in unaffected female adolescents.

Infants with Congenital Adrenal Hyperplasia Exhibit Thalamic Discrepancies in Early Brain Structure

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) have prenatal and postnatal hormonal imbalances. To characterize the ontogeny of reported brain and behavior changes in older children with CAH, we aimed to study the brain structure in infants with CAH compared to healthy controls. Methods: We performed neuroimaging in 16 infants with classical CAH due to 21-hydroxylase deficiency (8 males, gestational age 38.2 ± 1.7 weeks, post-conceptional age [PCA] 42.2 ± 3.0 weeks) and 14 control infants (9 males, gestational age 38.5 ± 1.8 weeks, PCA 42.5 ± 2.4 weeks) utilizing 3-Tesla magnetic resonance imaging. Regional brain volumes were adjusted for PCA and sex, along with an additional adjustment for total brain volume (TBV), for group comparisons by regression analyses (mean, 95% confidence interval [CI]). The degree to which each brain region was differentiated between CAH and control infants was examined by relaimpo analyses, adjusting for all other brain regions, PCA, and sex. Results: Infants with CAH had significantly smaller thalamic volumes (8,606 mm³, 95% CI [8,209, 9,002]) compared to age-matched control infants (9,215 mm³, 95% CI [8,783, 9,647]; β = −609; p = 0.02) which remained smaller after further adjustment for TBV. Upon further adjustment for TBV, the temporal lobe was larger in infants with CAH (66,817 mm³, CI [65,957, 67,677]) compared to controls (65,616 mm³, CI [64,680, 66,551]; β = 1,202, p = 0.03). The brain regions most differentiated between CAH versus controls were the thalamus (22%) and parietal lobe (10%). Conclusions: Infants with CAH exhibit smaller thalamic regions from early life, suggesting a prenatal influence on brain development in CAH. Thalamic emergence at 8–14 weeks makes the region particularly vulnerable to changes in the intrauterine environment, with potential implications for later maturing brain regions. These changes may take time to manifest, meriting longitudinal study through adolescence in CAH.

Electrolyte abnormalities and stress dosing predict illness-related hospitalizations among infants and toddlers with congenital adrenal hyperplasia.

Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for morbidity/mortality arising from life-threatening adrenal crisis. Management of acute illnesses in CAH requires an understanding of factors leading to emergency department (ED) visits and hospitalizations in the first few years of life. We, therefore, examined adrenal crisis at prehospital and ED stages of illness in young children with CAH as they related to medical outcomes. Retrospective cohort study of 39 children with CAH due to 21-hydroxylase deficiency (0-4 years of age) and 27 age-matched controls. ED visit, acute illness symptoms (fever, vomiting, diarrhoea) and other characteristics (hospitalizations, administration of stress-dose hydrocortisone, electrolyte abnormalities). CAH infants and toddlers had significantly higher rates of ED visits (0.50 [0.25-0.88] per person-year) than controls (0 [0-0] per person-year; p < .001). Moreover, CAH children under 6 months old had significantly higher rates of ED visits compared with older ages. Only 50% (51/102) of illness-related ED visits in CAH children were preceded by the administration of either oral (46/51) or intramuscular (11/51) stress dosing by parents. A total of 10.8% of ED visits resulted in hospital admission. Controlling for age and 17-hydroxyprogesterone at diagnosis, electrolyte abnormalities and administration of parenteral hydrocortisone in the ED significantly predicted hospital admission. Receiving a hydrocortisone injection before the ED was a significant predictor of having electrolyte abnormalities. Infants and toddlers with classical CAH are at high risk for acute illness and hospitalizations and often do not receive adequate stress dosing before the ED.

Components of Metabolic Syndrome in Youth With Classical Congenital Adrenal Hyperplasia.

Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common primary adrenal insufficiency in children, involving cortisol deficiency, hyperandrogenism, and cardiometabolic risk. Prior studies have reported that youth with classical CAH have a higher prevalence of the components of metabolic syndrome: obesity, hypertension, elevated fasting blood glucose, and dyslipidemia. Yet, the incidence of the complete metabolic syndrome itself in children and adolescents with CAH is relatively rare. Traditional cardiometabolic risk factors can surface early in children with classical CAH, and continue to present and evolve over the lifetime, although it is only recently that reports of Type 2 diabetes and adverse cardiac events have begun to surface in adults affected by this condition. The pathophysiology underlying the increased prevalence of cardiometabolic risk factors in patients with CAH is not well-understood, with disease treatments and androgen excess having been studied to date. The aim of this review is to evaluate the recent literature on traditional cardiometabolic risk factors in youth with classical CAH, and to consider non-traditional risk factors/biomarkers for subclinical atherosclerosis, inflammation, and insulin resistance. A better understanding of these traditional and non-traditional risk factors in youth with CAH could help guide treatment options and prevent the onset of metabolic syndrome in adulthood, reducing overall patient morbidity.

Weight Loss During Topiramate Treatment in a Severely Obese Adolescent with Congenital Adrenal Hyperplasia and Migraine

Youth with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit an increased prevalence of obesity, early adiposity rebound, and increased abdominal adiposity compared to unaffected youth. Current obesity management in CAH largely focuses on lifestyle modifications. There is evidence that topiramate therapy is effective in reducing body mass index (BMI), as well as visceral adipose tissue (VAT), in unaffected adolescents with exogenous obesity. However, little is known about the efficacy of topiramate in patients with classical CAH. We report on a 17-year-old female with severe obesity and salt-wasting CAH due to 21-hydroxylase deficiency, who demonstrated reductions in BMI, as well as abdominal visceral and subcutaneous adipose tissue (SAT) while on topiramate therapy. The patient was diagnosed with classical CAH as a newborn with a 17-hydroxyprogesterone 11,000 ng/dL. She had a BMI over the 95th percentile at 3 years of age, followed by unremitting obesity. At 17 years old, she was started on topiramate to treat chronic migraines. Following three years of topiramate therapy, her BMI z-score decreased from +2.6 to +2.1. After four years of therapy, her waist circumference decreased from 110 to 101 cm, abdominal VAT decreased substantially by 34.2%, and abdominal SAT decreased by 25.6%. Topiramate therapy was associated with effective weight loss and reduced central adiposity in an adolescent with classical CAH and severe obesity, without any side effects. Further study is warranted regarding topiramate therapy in obese youth with classical CAH and increased central adiposity, who are at higher risk for significant morbidity.

Low Adrenomedullary Function Predicts Acute Illness in Infants With Classical Congenital Adrenal Hyperplasia.

Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. This work aimed to study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. This prospective cohort study comprised participants recruited from a pediatric tertiary care center: 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main outcome measures included plasma epinephrine levels (N = 27), CYP21A2 genotype (N = 15), and incidence of acute illnesses from birth to age 1 year (N = 28). Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (β = -0.018, R = -0.45, P = .02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R = -0.51, P = .007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P = .02). CAH patients had lower epinephrine as newborns than did controls (P = .007) and showed decreases in epinephrine from birth to age 1 year (P = .04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

Gender-role behaviour and gender identity in girls with classical congenital adrenal hyperplasia

IntroductionGirls with classical congenital adrenal hyperplasia (CAH) are exposed to excess fetal adrenal androgens in-utero, and often born with masculinised genitalia. They are conventionally reared as females, but show more “boyish” gender-role behaviour (GRB) and gender-identity (GI) issues in childhood and adolescence. Male-rearing is also reported mainly due to delayed treatment and/or socio-cultural factors. We compared GRB/GI in girls with CAH with healthy age matched children, and explored for associations with socio-demographic and diagnosis/treatment related factors.MethodsGRB and GI were assessed using the Gender Identity Questionnaire for children (GIQC) in 27 girls with classical CAH at a specialised clinic, and compared with 50 age-matched healthy controls, with exploratory-analysis based on socio-demographic and diagnosis/treatment-related factors.ResultsGirls with CAH had lower total GIQC scores compared to healthy children (3.29 vs. 4.04, p = < 0.001) with lower GRB score (3.39 vs. 4.23, p < 0.001), and tendency for lower GI score (3.19 vs. 3.5, p = 0.08). Exploratory analysis showed no differences based on diagnosis/treatment factors including age, degree of virilisation at diagnosis and surgical procedures. and only subtle changes based on ethnicity and maternal education.Discussion/conclusionGirls with CAH managed at a specialised centre showed more masculinised GRB and tendency for ambiguous GI, which did not vary upon diagnosis/treatment related factors, suggesting that prenatal androgen exposure was the likely contributor. Clinicians should be vigilant about the increased risk of gender-related problems in girls with CAH, irrespective of sociocultural background and despite early treatment.

Early Adiposity Rebound Predicts Obesity and Adiposity in Youth with Congenital Adrenal Hyperplasia

Introduction: Youth with classical congenital adrenal hyperplasia (CAH) have higher prevalence of cardiometabolic risk factors such as obesity, abdominal adiposity, and hypertension. Patients with CAH also exhibit an earlier adiposity rebound (AR) compared to normative populations. However, the predictive relationship between AR and cardiometabolic risk factors needs to be better understood. Methods: We performed a retrospective cohort study at a US tertiary pediatric center in youth with classical CAH due to 21-hydroxylase deficiency. AR was determined by cubic polynomial modeling. A subset of participants had fasting analytes, whole-body dual-energy X-ray absorptiometry, and magnetic resonance imaging as adolescents. Results: In 42 youth with CAH (45.2% female, 54.8% Hispanic, and 90.5% salt-wasting form), the average age at AR was 3.4 ± 1.3 years. AR differed by BMI-z, with youth with obesity having an earlier AR (2.8 ± 1.0 years) compared to lean youth (4.1 ± 1.3 years, p = 0.001). However, AR did not differ by either CAH form or sex. Earlier AR predicted higher BMI-z at 7 and 12 years of age. In addition, earlier AR predicted increased central obesity (as measured by waist circumference, subcutaneous adipose tissue, and trunk fat) and total body fat in adolescence. AR was negatively correlated with bone age, and its relationships with HDL and hypertension were trending towards significance. Conclusions: AR in youth with classical CAH could serve as a useful clinical marker to identify those patients who are at higher risk for developing cardiometabolic risk factors during childhood and adolescence.

No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls

The 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: β = −0.001 (−0.008, 0.006); females: β = −0.004 [−0.015, 0.007]; males: β = 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.

SAT-097 Early Adiposity Rebound in Youth with Congenital Adrenal Hyperplasia Predicts Childhood Obesity and Adiposity in Adolescence

Purpose: Youth with classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency have an increased prevalence of obesity, abdominal adiposity, and fat mass compared to unaffected youth. As well, CAH youth in the United Kingdom (UK) have been found to have an earlier adiposity rebound (AR; rise in BMI corresponding to increased adipocyte size and number) at 1.7 years old, three years earlier than the general UK population. In unaffected youth, an earlier AR is predictive of obesity in adolescence. Our objective was to further understand the relationships between AR, weight status, and disease factors inherent to CAH in pediatric patients at our United States (US) center. Methods: In 45 youth with classical CAH, weight-for-length (kg/cm; if <2 yr) percentiles or BMI (kg/m2; if ≥2 yr) Z-scores were calculated every 6 months between the ages of 1 and 7 years, and at the patient’s last clinic visit. The cubic polynomial method was used to determine age at AR, located at the nadir before the second rise in the model. BMI-Z at the last clinic visit (12.6±3.8 yr) was used to classify final weight status as lean (Z<2) or obese (Z≥2). AR, and weight-for-length percentile at 1 yr, were analyzed for prediction of BMI-Z at 7 yr. Additionally, in a subset of 21 CAH youth enrolled in prior studies, total body fat and trunk fat (DXA), as well as abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT; single-slice CT or 3-T MRI at the level of the umbilicus) were cross-sectionally measured. Other CAH factors assessed in all youth included: glucocorticoid dose at AR, 17OHP at newborn diagnosis, and average bone age SD from clinical x-rays. Mann-Whitney U tests and Pearson correlations were used to assess group differences and associations. Simple linear regressions were used to predict childhood obesity and adolescent adiposity. Data are presented as mean±SD. Results: Age at AR for CAH youth was 3.1±1.4 yr, which is earlier than the normative US population (5.5 yr). Stratifying youth by weight status at their last clinic visit, age at AR was earlier in obese (2.5±1 yr, n=23) versus lean (3.7±1.6 yr, n=22; p<0.01) youth. AR strongly predicted BMI-Z at 7 yr (R= -0.65, β= -0.27, p<0.001) whereas weight-for-length percentile did not (R=0.22, p=0.14). AR was negatively correlated with total body fat (R= -0.58, p<0.01), trunk fat (R= -0.60, p<0.01), and abdominal SAT (R= -0.60, p<0.01), but not with VAT (R= -0.24, p=0.3). There were no associations between AR and glucocorticoid dose or newborn 17OHP. However, AR was negatively correlated with bone age SD (R= -0.37, p=0.05). Conclusion: Youth with CAH at our center exhibited an earlier AR by two years compared to the normative US population. This earlier AR was predictive of obesity in childhood, as well as increased total body fat and central adiposity in adolescence. Further study of disease-specific factors such as genotype in CAH are merited.

Absence of Testicular Adrenal Rest Tumors in Newborns, Infants, and Toddlers with Classical Congenital Adrenal Hyperplasia

Introduction: Testicular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH. Objective: We assessed the presence of TART in newborn, infant, and toddler males with classical CAH via scrotal ultrasound. Methods: Males with CAH had scrotal ultrasounds during the first 4 years of life, evaluating testes for morphology, blood flow, and presence of TART. Newborn screen 17-hydroxyprogesterone (17-OHP) and serum 17-OHP at the time of ultrasound were recorded. Bone ages were considered very advanced if ≥2 SD above chronological age. Results: Thirty-one ultrasounds in 16 males were performed. An initial ultrasound was obtained in four newborns at diagnosis (6.8 ± 2.1 days), six infants (2.2 ± 0.9 months), and six toddlers (2.4 ± 0.9 years). Eleven males had at least one repeat ultrasound. A large proportion (11/16) were in poor hormonal control with an elevated 17-OHP (325 ± 298 nmol/L). One infant was in very poor hormonal control (17-OHP 447 nmol/L) at initial ultrasound, and two toddlers had advanced bone ages (+3.2 and +4.5 SD) representing exposure to postnatal androgens. However, no TART were detected in any subjects. Conclusions: TART were not found by scrotal ultrasound in males up to 4 years of age with classical CAH despite settings with expected high ACTH drive. Further research into the occurrence of TART in CAH may elucidate factors that contribute to the detection and individual predisposition to TART.

SUN-281 Topiramate-Induced BMI Reduction in an Adolescent with Severe Obesity Associated with Classical Congenital Adrenal Hyperplasia

Background: Youth with classical congenital adrenal hyperplasia (CAH) exhibit up to double the prevalence of obesity, earlier adiposity rebound, and increased abdominal adiposity and total fat mass compared to unaffected individuals. Lifestyle modification often results in suboptimal body mass index (BMI) reduction. Therefore, more aggressive interventions, such as anti-obesity pharmacotherapies, should be considered in this high-risk cohort. There is growing evidence that topiramate therapy is effective in reducing BMI in adults and adolescents with severe exogenous obesity. However, little is known about the efficacy of topiramate in severe obesity associated with CAH. Case Presentation: We report a 17-year-old female with salt-wasting CAH due to 21-hydroxylase deficiency, and severe obesity since early childhood, who demonstrated significant and sustained BMI reduction while on topiramate therapy prescribed for chronic migraines. She was diagnosed shortly after birth with CAH (17-hydroxyprogesterone 11,000 ng/dL) and treated with hydrocortisone, fludrocortisone, and salt supplementation. She was also noted to have craniosynostosis at birth, and developed generalized tonic-clonic seizures at age 3 months, necessitating phenobarbital therapy for 4 years. Her BMI was > 95th percentile at age 3 years. At age 14 years, she developed chronic migraine headaches and, at age 17 years, was started on topiramate (50 mg daily) by her neurologist. At the time of topiramate initiation, she was on lifestyle modification treatment for obesity, with a BMI 48.3 kg/m2 (BMI z-score +2.2 SD; weight 100.2 kg). Topiramate was titrated up to 100 mg daily over a period of 1 year, and she remained on the same dose, with a BMI 37.8 kg/m2 (weight 79.0 kg) at age 21 years. Her glucocorticoid dose at topiramate initiation was 15 mg/m2/day and 15.3 mg/m2/day at age 21 years. She did not have any episodes of adrenal crisis during topiramate therapy. Body composition studies obtained pre- and post-topiramate therapy showed a decrease in total body fat (51.9 to 45.9%) and trunk fat (45.8 to 40%) on whole-body DEXA scan, as well as a decrease in waist-to-height ratio (0.76 to 0.70). Conclusions: Youth with classical CAH and associated severe obesity are at high risk for morbidity and could therefore benefit substantially from innovative medical therapies for obesity beyond lifestyle modification. In our patient, topiramate produced a clinically meaningful and sustained weight loss, in addition to reduced total body and trunk fat over a 4-year period. Although there exists a single report of topiramate-induced hypoadrenalism in patients with CAH (Jacob et al, BMJ 2009), our patient had neither an increased frequency of adrenal crisis nor an increased glucocorticoid requirement during her treatment course. Further study is warranted to investigate the use of topiramate as treatment for severe obesity in CAH.

Improved medical-alert ID ownership and utilization in youth with congenital adrenal hyperplasia following a parent educational intervention.

Classical congenital adrenal hyperplasia (CAH) is a potentially life-threatening condition, and adrenal crisis is a major cause of morbidity and mortality in affected children. Medical-alert identification (ID) could prevent complications of adrenal crisis by identifying the need for time-sensitive, critical treatment. Our objectives were to evaluate usage of medical-alert IDs by CAH youth, ownership and awareness of IDs amongst their parents, and the effect of an in-clinic educational intervention on ID utilization. Fifty families of youth with classical CAH secondary to 21-hydroxylase deficiency (11.2±5.0 years old, 58% female) were prospectively studied. An in-clinic needs assessment survey was administered at baseline to parents, paired with an educational intervention, and a follow-up needs assessment phone survey 1 month post-intervention. A quality improvement (QI) framework was utilized with plan-do-study-act (PDSA) process-improvement cycles. At baseline, 20/50 (40%) CAH families owned a medical-alert ID, of which only 10/20 (50%) of ID owners reported usage >3 days per week. Only 26/50 (52%) parents were aware of ID options. Post-intervention, ID ownership doubled to 39/50 (78%; p<0.05), usage amongst ID owners reached 100% (39/39), and awareness increased to 42/50 (84%; p<0.05). A surprising barrier reported by five Spanish-speaking families was the inability to order medical-alert IDs online. Only a small percentage of CAH youth frequently wear a medical-alert ID, but utilization can be effectively improved with an in-clinic educational intervention. Further study is merited to assess a potential reduction in morbidity and mortality of adrenal crisis with increased medical-alert ID utilization.

Stigma Associated with Classical Congenital Adrenal Hyperplasia in Women's Sexual Lives.

The risk of intersex-related stigma often serves as social indication for "corrective" genital surgery, but has not been comprehensively documented. In preparation for the development of an intersex-specific stigma assessment tool, this qualitative project aimed to explore stigma in girls and women with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. As part of a comprehensive follow-up project, 62 adult women with classical CAH (age range 18-51years) took part in an open-ended retrospective interview focusing on the impact of CAH and its treatment on various aspects of girls' and women's lives. Deductive qualitative content analysis (Patton, 2014) of de-identified transcripts involved categorization of three types of stigma: experienced, anticipated, and internalized. Two-fifths of the participants reported CAH-related stigma in romantic/sexual situations. Stigma enactment by romantic partners occurred in reaction to both genital and non-genital sex-atypical features of CAH and sometimes included explicit questioning of the women's true gender. Stigma anticipation by the women and their related avoidance of nudity, genital exposure, and romantic involvement altogether were frequent. Internalization of stigma occurred as well. In conclusion, the data suggest that many women with CAH experience, anticipate, and/or internalize intersex-related stigma in the context of their romantic/sexual lives.

Syndrome-Related Stigma in the General Social Environment as Reported by Women with Classical Congenital Adrenal Hyperplasia.

Stigma defined as "undesired differentness" (Goffman, 1963) and subtyped as "experienced" or "enacted," "anticipated," and "internalized" has been documented for patients with diverse chronic diseases. However, no systematic data exist on the association of stigma with somatic intersexuality. The current report concerns women with classical congenital adrenal hyperplasia (CAH), the most prevalent intersex syndrome, and provides descriptive data on CAH-related stigma as experienced in the general social environment (excluding medical settings and romantic/sexual partners) during childhood, adolescence, and adulthood. A total of 62 adult women with classical CAH [41 with the salt-wasting (SW) variant and 21 with the simple-virilizing (SV) variant] underwent a qualitative retrospective interview, which focused on the impact of CAH and its medical treatment on many aspects of women's lives. Deductive content analysis was performed on the transcribed texts. The women's accounts of CAH-related stigma were identified and excerpted as vignettes, and the vignettes categorized according to social context, stigma type, and the associated features of the CAH condition. Nearly two-thirds of women with either variant of CAH provided stigma vignettes. The vignettes included all three stigma types, and most involved some somatic or behavioral feature related to sex or gender. Stigma situations were reported for all ages and all social contexts of everyday life: family, peers, colleagues at work, strangers, and the media. We conclude that there is a need for systematic documentation of stigma in intersexuality as a basis for the development of improved approaches to prevention and intervention.

Decreased adrenomedullary function in infants with classical congenital adrenal hyperplasia.

Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can cause life-threatening adrenal crises as well as severe hypoglycemia, especially in very young children. Studies of CAH patients 4 years old or older have found abnormal morphology and function of the adrenal medulla and lower levels of epinephrine and glucose in response to stress than in controls. However, it is unknown whether such adrenomedullary abnormalities develop in utero and/or exist during the clinically high-risk period of infancy and early childhood. The objective of the study was to characterize adrenomedullary function in infants with CAH by comparing their catecholamine levels with controls. Design/Settings: This was a prospective cross-sectional study in a pediatric tertiary care center. Plasma epinephrine and norepinephrine levels were measured by HPLC. Infants with CAH (n = 9, aged 9.6 ± 11.4 d) had significantly lower epinephrine levels than controls [n = 12, aged 7.2 ± 3.2 d: median 84 [(25th; 75th) 51; 87] vs 114.5 (86; 175.8) pg/mL, respectively (P = .02)]. Norepinephrine to epinephrine ratios were also significantly higher in CAH patients than controls (P = .01). The control infants had primary hypothyroidism, but pre- and posttreatment analyses revealed no confounding effects on catecholamine levels. This study demonstrates for the first time that infants with classical CAH due to 21-hydroxylase deficiency have significantly lower plasma epinephrine levels than controls, indicating that impaired adrenomedullary function may occur during fetal development and be present from birth. A longitudinal study of adrenomedullary function in CAH patients from infancy through early childhood is warranted.

Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Background:There are recommendations regarding the total dose of hydrocortisone to be administered in the treatment of classical congenital adrenal hyperplasia (CAH) to achieve the twin objectives of glucocorticoid replacement and control of hyperandrogenism. However, there is evidence gap regarding the breakup, timing and type of the steroid regimen.Objectives:Efficacy of three different glucocorticoid regimens having the same total dose of steroid, differing in either the timing or type of evening steroid administered, in achieving biochemical control of the disease was assessed.Materials and Methods:The study was done in 13 prepubertal children with classical CAH over a 6-month period with 2 months devoted to each regimen. We used a prospective cross-over design using 10-15 mg/m2 total dose of hydrocortisone. Two-fifths of the total dose of hydrocortisone was administered in the morning and one-fifth of the total dose was administered at noon in all the regimens. The regimens differed in the timing of the evening dose of hydrocortisone, 06.00-07.00 pm in regimen 1 and 09.00-10.00 pm in regimen 2. The third regimen had the evening dose of hydrocortisone replaced by an equivalent dose of prednisolone suspension which was administered at 10.00 pm. Serum 17-hydroxyprogesterone and testosterone levels were compared to assess the efficacy of treatment regimens.Results:The three different regimens were found to be similar in their ability to control 17-hydroxyprogesterone and testosterone levels. The percentage of patients with predefined criteria for biochemically controlled disease was similar in all the three regimens. However, there was a trend toward better control of 17-hydroxyprogesterone levels in patients receiving evening dose of prednisolone.Conclusions:There is no significant advantage in administering the hydrocortisone dose late at night in patients with classical CAH.

Overestimation of final height prediction in patients with classical congenital adrenal hyperplasia using the Bayley and Pinneau method

A typical growth pattern with decreased pubertal growth spurt has been identified in patients with classical congenital adrenal hyperplasia (CAH). To evaluate the accuracy of final height predictions in patients with CAH using the Bayley and Pinneau (B&P) method. Using growth and final height data of 92 patients (57 F/35 M) with CAH due to 21-hydroxylase deficiency (38 SV/54 SW), final height predictions with the B&P method were compared to actual final heights. In females, mean final height was 159.9 +/- 5.3 cm (-1.0 +/- 0.7 SDS) compared to predicted mean final height of 167.9 +/- 10.7 cm (+0.5 +/- 1.7 SDS), p < 0.001, overestimation 7.3 +/- 9.5 cm. In males, mean final height was 170.1 +/- 6 cm (-1.2 +/- 0.8 SDS) compared to predicted mean final height of 185.6 +/- 13.4 cm (+1.2 +/- 1.9 SDS), p < 0.001, overestimation 13.9 +/- 10.8 cm. In classical CAH, final height prediction using the B&P method results in significant overestimation of final height.

Increased large artery intima media thickness in adolescents with either classical or non-classical congenital adrenal hyperplasia.

Increased artery intima-media thickness (IMT) was found in adults with classical congenital adrenal hyperplasia (CAH). No data are available in patients with non-classical (NC) CAH. To evaluate IMT in adolescents with classical and NC CAH and to compare the results with those recorded in a control population. Eighteen adolescents with either classical (Subgroup A1) or NC CAH (Subgroup A2) were compared with 16 controls (Group B). All subjects underwent IMT ultrasonography measurement at different sites; results were correlated with clinical, metabolic, and insulin resistance (IR) data. When compared with Group B, both subgroups exhibited higher IMT values at all sites. No differences were found between classical and NC CAH. Univariate analysis of factors impacting on IMT of CAH patients demonstrated that: a) abdominal aorta (AA) IMT was positively correlated with cumulative glucocorticoid doses, triglyceride serum levels, and diastolic blood pressure SD score and negatively with androstenendione and ACTH levels; b) common carotid (CC) IMT was positively associated with triglycerides and triglyceride/HDL ratio. At multiple regression analysis, the independent positive predictors of AA and CC IMT were respectively triglyceride levels and triglyceride/HDL ratio. a) Even adolescents with NC CAH and not only those with classical form may be at higher risk of artery alterations; b) this risk is not necessarily associated with either obesity or waist/height ratio or dyslipidemia; c) an important role in the pathogenesis of artery alterations in CAH may be played by intermittent iatrogenic hypercortisolism and secondary IR.

Growth Patterns in the First Three Years of Life in Children with Classical Congenital Adrenal Hyperplasia Diagnosed by Newborn Screening and Treated with Low Doses of Hydrocortisone

Background: Linear growth is the best clinical parameter for monitoring metabolic control in classical congenital adrenal hyperplasia (CAH). Objective: To analyze growth patterns in children with CAH diagnosed by newborn screening and treated with relatively low doses of hydrocortisone during the first year of life. Patients and Methods: 51 patients (27 females) were diagnosed with classical CAH by newborn screening. All patients were treated with relatively low doses of hydrocortisone (9–15 mg/m² body surface area). 47 patients were additionally treated with fludrocortisone. Results: At birth, height SDS (H-SDS) was 1.1 ± 1 in girls and 0.9 ± 1.5 in boys. After 3 months, H-SDS decreased to 0.4 ± 0.9 in girls and to 0.1 ± 1.3 in boys. Over the 3-year period, H-SDS further decreased to –0.4 ± 1.8 in girls and to –0.8 ± 1 in boys and approached the genetic height potential (target H-SDS of girls –0.5 ± 0.3 and target H-SDS of boys –0.9 ± 0.7). During the first 9 months of age, growth velocity was slightly decreased in girls (18.2 ± 1.9 cm) and boys (17.3 ± 1.6 cm) when compared to a healthy reference population (girls 19.0 ± 3.9 cm and boys 18.7 ± 4.7 cm). At the age of 3 years, bone age was appropriate for chronological age in both girls (2.7 ± 0.5 years) and boys (2.9 ± 0.5 years). Conclusion: Birth length is above average in children with classical CAH, which might be the result of untreated hyperandrogenism in utero. With relatively low doses of hydrocortisone treatment, growth velocity decreases slightly during the first 9 months and H-SDS then approaches the genetic height potential.