Congenital Adrenal Hyperplasia Group Research Articles

Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

ODP394 Prevalence of Anxiety and Depressive Symptoms in Children and Adolescents with Congenital Adrenal Hyperplasia (CAH)

Abstract Background CAH is a life-long inherited condition in which individuals require multiple daily doses of medication and are at risk for life-threatening adrenal crises. Adult studies have demonstrated increased rates of psychiatric morbidity with CAH. Given the chronicity and severity of CAH, children are at risk for psychiatric morbidity as well. This study aimed to examine the prevalence of anxiety and depressive symptoms in children and adolescents with CAH. Method: This was a cross-sectional cohort study in which children and adolescents (ages 7-17 years) with CAH (classical or non-classical, on steroid treatment) and their parents were recruited from our institution's urban outpatient clinics from May to December 2021. Healthy, well-controlled children and adolescents with congenital or autoimmune hypothyroidism (HT) and their respective parents served as control participants. Children and adolescents completed questionnaires, based on age eligibility: Screen for Child Anxiety Related Disorders (SCARED), Children's Depression Inventory 2 Self Report – Short (CDI-2), and Patient Health Questionnaire modified for Adolescents (PHQ-A). Parents completed respective parent-proxy questionnaires. Higher scores indicated greater symptoms of anxiety and depression. "At risk" scores were specific to each questionnaire. Measures were completed at a clinic visit, and demographic and past medical history were collected via a separate survey and the electronic medical record. Results A total of 58 child-parent dyads completed questionnaires. Thirty-two children had CAH (66% female, age 11.4 ±2.6 years, CAH duration 8.9 ±3.9 years) and 26 had HT (73% female, age 12.7 ±2.9 years, HT duration 6. 0±4.2 years). Thirty-two, 30 and 13 CAH children and 25, 26 and 16 HT children completed the SCARED, CDI-2 and PHQ-A, respectively. There was no significant difference in level of anxiety and depressive symptoms in children with CAH as compared to the HT group (SCARED 19 ±12 vs. 26±17, P=0.200; CDI-2 53±11 vs. 55±11, P=0.400). The CAH group had fewer depressive symptoms than the HT group on the PHQ-A (4±6 vs 6±5, P=0. 038). There was no difference in rate of "at risk" scores between the CAH and HT groups (SCARED 33% vs. 44%, P=0.400; CDI-2 24% vs. 31%, P=0.500; PHQ-A 15% vs. 31%, P=0.400). No adolescent participants were found to have active suicidal ideation or intent. Children with CAH were more likely to score higher than parent-proxy responses for anxiety-related disorder (19 ±12 vs. 10±8, P=0. 003) and depressive symptoms (CDI-2 53±11 vs. 49±10, P=0. 046). Conclusions Prevalence of anxiety and depressive symptoms does not appear to be higher in children and adolescents with CAH as compared to controls. There is a lack of agreement between child and parent-proxy responses with parents endorsing fewer anxiety and depression symptoms than children. Findings suggest that children with CAH may benefit from routine mental health evaluations as part of CAH care and not only after voiced parental concern. Presentation: No date and time listed

Psychosocial Impact of the COVID-19 Pandemic on Children with Congenital Adrenal Hyperplasia and Their Families.

This study aimed to investigate the psychosocial impact of the pandemic in pediatric patients with congenital adrenal hyperplasia and their families and whether congenital adrenal hyperplasia imposes an additional burden compared to other endocrine disorders. Patients with congenital adrenal hyperplasia (n = 38) and congenital hypothyroidism (n = 41) and their families were enrolled in the prospective longitudinal survey study. Questionnaires that were completed remotely in June 2020 and in July 2021 included Depression Anxiety Stress Scale short form, The State-Trait Anxiety Inventory for Children, and purpose-built daily routine, parent, and child COVID information scores, factors affecting drug usage, and parents' thoughts about the pandemic. At the end of 1 year, Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children were repeated in the congenital adrenal hyperplasia group and they were questioned about the incidence and severity of coronavirus infection. Median Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children scores were similar between the congenital adrenal hyperplasia and congenital hypothyroidism groups. In the congenital adrenal hyperplasia group, median purpose-built daily routine was higher in those who had a State-Trait Anxiety Inventory for Children-State score above the threshold (P = .048), also Depression Anxiety Stress Scale short form-Depression, Depression Anxiety Stress Scale short form-Anxiety, Depression Anxiety Stress Scale short form-Stress, Parent COVID Information Score were higher among parents who followed news/data because of chronic diseases/medications of the child (P = .010, P = .034, P = .044, P = .045, respectively), and State-Trait Anxiety Inventory for Children-State was higher among parents who believed "having chronic diseases" and "using medications" increase the risk of COVID-19 infection (P = .011, P = .016, respectively). In the second survey, State-Trait Anxiety Inventory for Children-State, Depression Anxiety Stress Scale short form-Anxiety, and Depression Anxiety Stress Scale short form-Stress decreased significantly (P < .01, P = .009, P = .008, respectively). Three patients with congenital adrenal hyperplasia who reported positive nasopharyngeal swab tests revealed mild symptoms. The pandemic has negative consequences on the mental well-being of individuals with chronic diseases, albeit from different causes.

Analysis of clinical features and etiological diagnostic indices of reproductive age women with hyperandrogenism

Objective: To investigate the clinical features and the value of different diagnostic indices for etiology in reproductive age women with hyperandrogenism. Methods: The medical records of 96 reproductive age women with hyperandrogenism in the multi-disciplinary team of Peking University First Hospital from January 2020 to April 2021 were collected. The patients were divided into four groups based on final diagnosis: congenital adrenal hyperplasia (CAH) (n=8), polycystic ovary syndrome (PCOS) (n=67), idiopathic hyperandrogenism (n=13) and other specific diseases (n=8), respectively. The indices related to androgens in different groups were compared, and then their efficiency for diagnosis of CAH and PCOS were analyzed with receiver operator characteristic curve (ROC curve). Results: A total of 96 patients with hyperandrogenism were recruited, with the age of 19-45 (29±6) years old. Overall, 4.2% (4/96) of the patients were with single clinical hyperandrogenism, 56.3% (54/96) were with single laboratory hyperandrogenaemia and 39.6% (38/96) were with both. The breakdown into laboratory hyperandrogenaemia subtypes was as follows: only T elevation 22.8% (21/92), only A2 elevation 7.6% (7/92), none DHEAS elevation, only FAI elevation 5.4% (5/92) and elevation of more than one of the androgen indices mentioned above accounted for 64.1% (59/92). In the reasons of consultation, simple irregular menstruation (36.0%, 32/89) or accompanied by clinical hyperandrogenism with or without infertility (36.0%, 32/89) were the most common. As for primary visiting departments, Obstetrics and Gynecology accounted for 53.2% (51/96), and then Endocrinology as 39.5% (38/96). The 17-OHP level of CAH, PCOS and idiopathic hyperandrogenism group was 20.0 (8.2, 33.1), 1.1 (0.8, 1.4), 0.9 (0.8, 1.3) ng/ml, respectively. The androstenedione level in these groups was 6.3 (4.6, 8.7), 3.8 (2.9, 4.8) and 3.2 (2.7, 3.7) ng/ml, respectively. The 17-OHP and androstenedione levels of CAH group were significantly higher than that in PCOS or idiopathic hyperandrogenism group (all P<0.05). The ratio of LH and FSH in these three groups was 0.8(0.5, 1.0), 1.3(0.6, 1.9) and 0.6(0.3, 0.7), respectively. The ratio of LH and FSH was significantly higher in PCOS than that in idiopathic hyperandrogenism group (P=0.024), but yet there was no significant difference compared with CAH group (P>0.05). The AUC of ROC curve of 17-OHP for CAH diagnosis was 0.94, followed by androstenedione 0.83, whereas LH/FSH for PCOS diagnosis was only 0.63. Conclusions: Among the reasons of consultation in reproductive age women who visited our multi-disciplinary team for female hyperandrogenism, simple irregular menstruation or accompanied by clinical hyperandrogenism with or without infertility are the most common. PCOS accounts for the majority of different androgen excess disorders. 17-OHP is the most valuable parameter for the diagnosis of CAH and secondly androstenedione.

Sexual function in adult females after feminizing genitoplasty for congenital adrenal hyperplasia

To investigate sexual function and subjective attitudes towards surgery in adult women after feminizing genitoplasty (FG) for congenital adrenal hyperplasia (CAH). We retrospectively reviewed the medical files of patients who underwent FG from 1996 to 2018. Of those, patients older than 16 years of age were asked to answer non-standardized questions aiming at the awareness of genital surgery and standardized questionnaire evaluating sexual function (GRISS). The anonymized answers were compared to a control group of 50 healthy females. Student's t-test, Pearson's χ2 test, Fisher's exact test and Spearman's rank correlation coefficient were performed. A P-value less than 0.05 was considered significant. Out of 106 patients who underwent FG, 64 were included, 55 successfully contacted and 32, aged 17-40 years (median 25.5), answered the questionnaires (58% response rate). In all, 11 patients underwent historical clitorectomy in early childhood by a pediatric gynecologist before 1996 and pull-through vaginoplasty at puberty. A total of 21 patients underwent modern one- or two-staged FG. There were statistically significant differences between the CAH group and controls as to the proportion living in committed partnerships (28% and 84%, respectively; p=0.0000), having sexual intercourse (41% and 92%, respectively; p=0.0000) and having their own children (13% and 36%, respectively; p=0.0369). The median overall GRISS score was 4 (range 1-7) in the CAH group compared to 1 (range 1-9) in the control group, with infrequency and vaginismus representing the least favorable subscales (median 5). In all, 81% of the women operated on for CAH would recommend such an operation to any other individual with CAH and 66% of them suggested the surgery should be performed in early childhood. By this study we have contributed to the debate over suggestions that FG may cause adverse effects on sexual life of the patients in adulthood, beside already published effects on their mental well-being and LUTS. Despite possible selection bias due to only 58% response rate the comparison with control group shows only a moderate sexual dysfunction and more significant impact on long-term partnership that might be caused by other factors related to CAH beside FG itself. Partnership, offspring, sexual frequency and function were impaired in adult females with CAH after FG. However, the median GRISS score was below the pathological level of 5.

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aimWe aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH).Materials and methods Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system.Results There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status.Conclusion In this study, the CIMT values of CAH cases were similar to those of healthy subjects.

Vocal profile of 46,XX individuals with congenital adrenal hyperplasia.

Describe the vocal profile of 46,XX congenital adrenal hyperplasia (CAH) patients followed up at the Genetics Outpatient Clinic of the Federal University Bahia (GOC-UFBA). This is a descriptive, exploratory, cross-sectional study. The study sample consisted of 28 volunteers: 14 individuals diagnosed with CAH, followed up by the multiprofessional team of the GOC-UFBA, and 14 46,XX individuals without vocal changes and endocrine and/or genetic pathologies. Voice sample collection was performed individually in a quiet environment with participants properly seated. Acoustic (PRAAT program) and auditory-perceptual (Consensus Auditory-Perceptual Evaluation of Voice - CAPE-V) analyses were conducted. In the qualitative assessment of pitch, eight (61.54%) patients in the CAH group showed low vocal pattern and eight (61.54%) individuals in the group without CAH presented high vocal pattern. There were statistically significant differences between the groups only for the following vocal attributes of the CAPE-V: overall severity (p=0.01), roughness (p=0.00), and pitch (p=0.01). No statistically significant difference was observed in the other acoustic parameters investigated (p>0.05). The present study demonstrated that 46,XX CAH individuals, even when submitted to hormone therapy, present rough, low, deviant voice.

Pregnancy, delivery and neonatal outcomes among women with congenital adrenal hyperplasia: a study of a large US database

Research questionWhat is the association between congenital adrenal hyperplasia (CAH) and pregnancy, delivery and neonatal outcomes, using a population database cohort. DesignRetrospective study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database from 2004–2014. ICD-9 code 255.2 was used to extract the cases of CAH. Pregnancies complicated with CAH were compared with the other pregnancies. All confounding variables were adjusted using multivariate logistic regression, based on any significant differences between the two groups. ResultsA total of 9,096,788 deliveries occurred during the study period. Two hundred and ninety-nine pregnant women had CAH. Chorioamnionitis was higher in CAH compared with controls after controlling for risk factors (adjusted OR 2.67, 95% CI 1.17 to 6.06). The rates of caesarean section and maternal infection were also higher in CAH than controls (adjusted OR 2.10, 95% CI 1.44 to 3.07 and adjusted OR 2.63, 95% CI 1.22 to 5.63, respectively). Risk of gestational diabetes and pregnancy-induced hypertension rates were not significantly different in CAH (adjusted OR 1.53, 95% CI 0.91 to 2.58 and adjusted OR 0.87, 95% CI 0.49 to 1.56, respectively). At birth, 8% and 2.2% of the neonates were found to be small for gestational age in the CAH and the control groups, respectively (adjusted OR 3.37, 95% CI 1.86 to 6.11). Congenital anomalies were encountered in 2.7% and 0.4% in the CAH and control groups, respectively (adjusted OR 5.24, 95% CI 2.31 to 11.90). ConclusionsWomen with CAH were at risk of complications and fetal anomalies. Expected increases in rates of hypertension and gestational diabetes were not encountered. These patients will benefit from surveillance to decrease morbidity.

Sexual function in women with androgen excess disorders: classic forms of congenital adrenal hyperplasia and polycystic ovary syndrome

PurposeWe compared the sexual function in women with classic forms of congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS) to find if the cause of androgen excess determines sexual functioning.MethodsHundred and four women (21 with CAH, 63 with PCOS and 20 healthy controls) aged 18–40 years were included into the study. All participants completed a questionnaire regarding their sociodemographic background and underwent anthropometric and basic biochemical measurements. Plasma levels of total testosterone, androstenedione, and 17-hydroxyprogesterone were measured with immunoassay. To assess the sexual functions, the Female Sexual Function Index (FSFI) questionnaire was applied.ResultsApart from the higher physical activity in PCOS patients (P = 0.017), we found no significant sociodemographic differences between the studied groups. In clinical assessment, women with CAH had a lower incidence of acne (P = 0.006). Their plasma levels of 17OHP (P = 0.005) and insulin resistance index (P = 0.0248) were higher, while total testosterone (P = 0.0495) and glucose (P = 0.0061) was lower compared to the PCOS group. Significantly more women with CAH were homosexual (P = 0.003) and bisexual (P = 0.006). CAH group showed a lower total FSFI score (P = 0.0043) and lower scores in three domains: lubrication (P = 0.0131), sexual satisfaction (P = 0.0006), and dyspareunia (P < 0.0001). Higher physical activity was associated in all women with higher total FSFI score (P = 0.009) and scores in the domain of desire (P = 0.034) and sexual satisfaction (P = 0.01), while in CAH women apart from the total score (P = 0.03) and sexual satisfaction (P = 0.002) also in the domains of orgasm (P = 0.005), and pain (P = 0.03).ConclusionsCAH women present more often homosexual and bisexual orientation, while their sexual functions are impaired compared to PCOS patients.

Sexual function and health status in adult patients with Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia (CAH) is the most common reason for undifferentiated genital appearance in new-borns. Psychosexual outcome in women with CAH has been rarely evaluated, but it seems to be one of the most important factors determining the indications for the surgical treatment of CAH. This is to assess sexual function and the health status (HS) in adult females with CAH who had feminizing genitoplasty in childhood. The protocol was approved by the Ethical Committee, and the hospital database was searched for patients with CAH who had genitoplasty between 1975 and 2000. 57 adult patients were identified, and 9 (18%) patients agreed to participate in the study. Mean age at operation was 5.4 years, and mean follow-up duration was 10.9 years. The Female Sexual Function Index (FSFI) was used to evaluate sexual function, and the 36-item Short Form Health Survey (SF-36) was used to evaluate their health status (HS). A FSFI score < 26,55 was classified as Female Sexual Dysfunction (FSD). The control group consisted of 10 adult female volunteers of comparable age, without any oncological or chronic diseases. Fisher's exact test was used for statistical analysis. All patients in the CAH group had female gender identity. One was homosexual, and one reported not having any sexual activity. In the control group, all patients had female gender identity. All were heterosexual and one reported not having any sexual activity. The sexual function in five domains and total score were similar in both groups. More pain was reported in the CAH group as compared with the control group, and it was statistically significant. In the CAH group, 5/9 patients had FSD. In the control group, 4/10 patients had FSD. The difference was statistically insignificant (p=0.66). Mean SF-36 score in the CAH group was 47.1 points, while it was 46.7 points in the control group. The testosterone level in all CAH patients was within the normal range (0.13-1.1ng/ml). The 17-OH progesterone level was above normal range in 5/9 (55.6%) patients with CAH. All women in the CAH group were hormonally treated. In the control group, all patients had a normal testosterone level (0.15-0.68ng/ml); the 17-OH progesterone level was in normal range in this group. We compared our results with the literature data, which used the same questionnaires as in our study. Health status and sexual function in the traceable CAH patients didn't differ from the control group.

Screening for congenital adrenal hyperplasia in infertile women with high androgenemia during childbearing age

Objective The causes of infertility are complex and diverse, and congenital adrenal hyperplasia (CAH) is often overlooked in screening for infertility. In this study, CAH was diagnosed in women with high androgenemia who were infertile during childbearing age, and the diagnosis and treatment of CAH in pregnant women was investigated. Methods This study included 20 women with high androgenemia and infertility in the childbearing age who were referred to the Endocrinology Department after visiting the Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University from December 2016 to April 2019. All patients were tested for blood hormone levels, glucose, and lipid metabolism, underwent ACTH stimulation test, uterus and bilateral ovarian B-ultrasound, adrenal computed cosmography (CT), etc. Full-length sequencing of the CYP21A2 gene was performed as necessary. Results Among the 20 women with hyperandrogenism who were infertile, there were 7 cases of CAH (35.0%), including 6 cases of 21-hydroxylase deficiency (21-OHD) confirmed by gene sequencing; 10 cases of polycystic ovary syndrome (PCOS); 3 cases of idiopathic hyperandrogenemia (IHA). Sex hormone results showed that testosterone in CAH group was significantly higher than that in PCOS group and IHA group [(4.4±2.0 vs 2.9±0.4, 2.8±0.8) nmol/L, P 0.05]. However, the 17-OHP (60 min) in CAH group was significantly higher than that in PCOS group and IHA group [(200.1±80.8 vs 3.1±1.2, 3.4±0.2) ng/ml, P<0.05]. Glucocorticoid therapy was given to patients with CAH, and 4 patients had successful pregnancy. No clinical symptoms of CAH and external genital malformations were found in the offspring of patients who had been delivered. Conclusions The ACTH stimulation test is of great significance in the differential diagnosis of CAH, especially 21-OHD. Genetic testing helps to identify the type of mutation in CAH patients. On the one hand, glucocorticoid therapy may improve the pregnancy rate of CAH patients, on the other hand, it can help to reduce the status of maternal high androgen and avoid masculine manifestation of female offspring. Key words: Infertility; Hyperandrogenism; Congenital adrenal hyperplasia; ACTH stimulation test

Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd-LIFE study.

In patients with congenital adrenal hyperplasia (CAH) type and doses of glucocorticoids used as well as sex hormone secretion during puberty have important actions on bone mineral density (BMD) in adulthood. To evaluate BMD in adult CAH patients depending on current glucocorticoid therapy and on androgen levels in adulthood and at age 16years. We included 244 CAH patients from the dsd-LIFE cohort (women n=147, men n=97; salt-wasting n=148, simple-virilizing n=71, nonclassical n=25) in which BMD and bloods were available. Clinical and hormonal data at age 16years were retrieved from patients' files. Simple-virilizing women showed lower BMD compared to salt-wasting women at trochanter (0.65±0.12 vs 0.75±0.15g/cm2 ; P<.050), whole femur T-score (-0.87±1.08 vs -0.16±1.24; P<.05) and lumbar T-score (-0.81±1.34 vs 0.09±1.3; P<.050). Fracture prevalence did not differ significantly between the CAH groups. Prednisolone vs. hydrocortisone only therapy caused worse trochanter Z-score (-1.38±1.46 vs -0.47±1.16; P<.050). In women lumbar spine, BMD correlated negatively with hydrocortisone-equivalent dose per body surface (r2 =0.695, P<.001). Furthermore, BMI at age 16years correlated positively with lumbar spine T-score (r2 =0.439, P=.003) and BMD (r2 =0.420, P=.002) in women. The androstenedione/testosterone ratio at age 16years correlated positively with lumbar spine Z-score in women (r2 =0.284, P=.024) and trochanter Z-score in men (r2 =0.600, P=.025). Higher glucocorticoid doses seemed to cause lower BMD especially in women. Prednisolone appeared to have more detrimental effects on BMD than hydrocortisone. Higher glucocorticoid doses (lower androstenedione/testosterone ratio) during adolescence may cause lower BMD in adulthood.

Urinary steroidomic profiles by LC-MS/MS to monitor classic 21-Hydroxylase deficiency

21-hydroxylase deficiency, the most common enzyme defect associated with congenital adrenal hyperplasia (CAH) is characterized by an impairment of both aldosterone and cortisol biosynthesis. Close clinical and biological monitoring of Hydrocortisone (HC) and 9α-Fludrocortisone (FDR) replacement therapies is required to achieve an optimal treatment. As frequent and repeated reassessments of plasma steroids, 17-hydroxyprogesterone (17-OHP), androstenedione (Δ4-A) and testosterone (TESTO) is needed in childhood, urine steroid profiling could represent an interesting non-invasive alternative.We developed and validated a LC-MS/MS method for the measurement of 23-urinary mineralocorticoids, glucocorticoids and adrenal androgens. The usefulness of steroid profiling was investigated on single 08h00 am-collected spot urine for discriminating between 61 CAH patients and their age- and sex-matched controls. CAH patients were split into two groups according to their 08h00 am-plasma concentrations of 17-OHP: below (controlled patients, n = 26) and above 20 ng/mL (uncontrolled patients, n = 35).The lower limit of quantification and the wide analytical range allows to assay both free and total concentrations of the main urinary adreno-corticoids and their tetra-hydrometabolites. Extraction recoveries higher than 75% and intra-assay precision below 20% were found for most steroids.Urinary steroids upstream of the 21-hydroxylase defect were higher in uncontrolled CAH patients. Among CAH patients, plasma and urinary 17-OHP were closely correlated. As compared to controls, steroids downstream of the enzyme defect collapsed in CAH patients. This fall was more pronounced in controlled than in uncontrolled patients. Androgens (Δ4-A, TESTO and the sum etiocholanolone + androsterone) accumulated in uncontrolled CAH patients. A strong relationship was observed between plasma and urinary levels of androstenedione. Daily doses and urinary excretion of both FDR and HC were similar in both CAH groups. Urinary FDR was inversely related to the sodium-to-potassium ratio in urine. A partial least squares discriminant analysis model allowed to classify the patient’s classes unaffected, controlled and un-controlled CAH patients based on urinary steroidomic profiles.Our LC-MS/MS method successfully established steroid profiling in urine and represents a useful and non-invasive tool for discriminating CAH patients according to treatment efficiency.

Application of cross-sectional area measurement under high frequency ultrasound in diagnosis of congenital adrenal hyperplasia in infants

Objective To disscuss the role of cross-sectional area measurement under high frequency ultrasound in the diagnosis of congenital adrenal hyperplasia (CAH) in infants. Methods The abdominal ultrasound images of 20 infants with CAH which were admitted to our hospital and clinical diagnosised from November 2013 to August 2018 were analyzed retrospectively. The size of adrenal glands were evaluated by measuring the maximum cross-sectional area.Fifty normal full-term infants were selected as control group synchronism. The size of adrenal glands between infants with CAH and normal infants were compared. The area under the curve (AUC) and best cutoff value were obtained by drawing ROC curve.Sensitivity and specificity were also obtained. Results There was significant difference in maximum cross-sectional area of adrenal gland between CAH group and control group[(129.70±37.34)mm2 vs (54.41±20.84)mm2, t=10.004, P=0.001]. The AUC of cross-sectional area measurement was 0.966, and best cutoff value was 87.5 mm2. The sensitivity and specificity were 95.0% and 92.5%. Conclusions High-frequency ultrasound is convenient and accurate in measuring the maximum cross-sectional area of adrenal gland in infants. Cross-sectional area measurement has high sensitivity and specificity to the diagnosis of CAH. The presence of CAH is highly suspected when the area of adrenal gland reached 87.5 mm2. Key words: Ultrasonography; Congenital adrenal hyperplasia; Infant; Cross-sectional area of adrenal gland

Impaired systolic and diastolic left ventricular function in children and adolescents with congenital adrenal hyperplasia receiving corticosteroid therapy.

The study included 44 children with the diagnosis of classic congenital adrenal hyperplasia and 39 healthy children whose age, pubertal status, and gender were similar to those of the patient group. Anthropometric parameters and 17-hydroxyprogesterone levels were measured, and bone age was calculated. The average daily hydrocortisone dose was calculated over the last 1-year file records. Hyperandrogenic state was defined according to bone age SD score (⩾2) and 17-hydroxyprogesterone levels (&gt;10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging. Patients had higher morphological parameters, such as left ventricular end-systolic diameter, interventricular septal thickness at end diastole, left ventricular posterior wall thickness at end diastole, left ventricular mass and index, than the control group (p&lt;0.05). On pulsed-wave and tissue Doppler echocardiography, significant subclinical alterations were observed in systolic (isovolumic contraction time), diastolic (isovolumic relaxation time), and global left ventricular functional (myocardial performance index) parameters in the congenital adrenal hyperplasia group compared to the control group (p&lt;0.05). In partial correlation analyses, after controlling the effect of hyperandrogenism, the mean hydrocortisone dosage was positively correlated with isovolumic relaxation time in congenital adrenal hyperplasia group (p&lt;0.05). This study demonstrated that the patients with congenital adrenal hyperplasia are at risk for left ventricular hypertrophy, systolic and diastolic myocardial subclinical alterations. Overtreatment may be responsible for the increased risk of myocardial dysfunction in patients with congenital adrenal hyperplasia.

Autistic feature and 2D:4D finger ratio relations children and adolescents with congenital adrenal hyperplasia

Objective: Because congenital adrenal hyperplasia (CAH) and autism spectrum disorders (ASD) is rarely seen, it is difficult to assess whether the increased incidence of ASD in girls with CAH. ASD behaviors and 2D: 4D finger ratio changes in patients with androgen overproduction have been reported. The aim of this study is determining the 2D:4D finger ratios and ASD features in girls with CAH and normal control group. Methods: The study group will consist of thirty female children and adolescents between the ages of 3 and 15 who are diagnosed with classic CAH who were followed at the Pediatric Endocrinology Department of Duzce University Medical Faculty Hospital. For the control group, 30 healthy children and adolescents equalized with CAH patients in terms of age and gender will be taken. Al patients and controls examined for psychiatric disorders. by clinicians Patients and control groups filled Autism Behavior Checklist and semistructured sociodemographic form that evaluated the gender, age, pregnancy and birth complications, history of mothers’ cigarette and alcohol use. 2D:4D ratios were measured in both of control and CAH groups. Findings: KAH group right and left hand 2D:4D ratios were statistically lower compared to controls and also lower 2D:4D ratios had association with high ABC scores. When compared with control group, CAH group ABC scores were significantly higher. In KAH group there was a positive correlation between 2D:4D ratios and ABC scores. Conclusion: In light of present study findings, suggest that high androgen may have effect on low 2D:4D ratios and high ASD symptoms. Further researches with a large sample are needed in this field.

Carotid Intima-Media Thickness Is Associated with Increased Androgens in Adolescents and Young Adults with Classical Congenital Adrenal Hyperplasia

Background/Aims: Youth with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency develop cardiovascular disease (CVD) risk factors of obesity and hypertension. Carotid intima-media thickness (CIMT), a marker of CVD risk, is increased in CAH young adults. We examined CIMT and its relationship with androgens and obesity in adolescents/young adults with CAH. Methods: Twenty CAH subjects (age 16 ± 3.3 years, 50% female) and 20 matched controls were studied cross-sectionally. Eight additional obese patients with CAH were included in within-group comparisons. CIMT by high-resolution ultrasound, androgens, anthropometry, bone age (BA), and metabolic/inflammatory markers were assessed. Results: Within the CAH group, CIMT correlated with 17-hydroxyprogesterone (r = 0.48, p < 0.05) and androstenedione (r = 0.46, p < 0.05), and was greater in obese subjects. CIMT was greater in CAH males than females, but similar among CAH females with advanced BA, CAH males with normal BA, and control males. There was no difference in CIMT between CAH and controls, although high-density lipoprotein was inversely correlated with CIMT in both groups. Conclusion: CIMT is associated with increased androgens in CAH adolescents and young adults, with loss of sex differences in CAH females with excess androgen exposure. Our findings highlight the importance of hormonal control for CVD prevention in CAH.

Should we question early feminizing genitoplasty for patients with congenital adrenal hyperplasia and XX karyotype?

BackgroundThere is a wide difference of opinion between the medical–surgical community and advocacy group regarding Disorders of Sexual Development (DSD) secondary to congenital adrenal hyperplasia (CAH) being ranked in the intersex category. This rupture is even more evident when the issue of genitoplasty is brought up. For physicians it is obvious and unequivocal that a person with CAH and an XX karyotype has a female gender identity, whereas associations tend to rank persons with CAH in the intersex category and advocate holding-off on surgical management. Material/MethodsA retrospective case study vs. control group, spanning over 40years, included 21 patients who were treated in 3 different centers. Each patient and their parents were contacted independently and interviewed regarding interpersonal relationships, psychological impact of genitoplasty, gender identity and opinion on optimal care management for this disorder. Three couples controls (parent–child) per CAH patients were used and matched according to age, sex assigned at birth and ethnic origin. ResultsSex assigned at birth seemed to concord with the gender identity perceived by the patients in 85.7% of cases. In fact, 89.7% of patients and 100% of parents felt that feminizing genitoplasty should be performed within the first year of life. There is however a significant difference compared to controls who felt that surgical management should occur later on in life. No difference was highlighted during childhood regarding parents–child relationships or social integration. However, during adolescence, the parents–child relationship tended to be significantly more painful for the CAH group. Integrating their parenting role was significantly harder for patients in the CAH-DSD group. In the population of CAH-DSD patients who had genitoplasty the level of sexual fulfillment was not lower to the one reported by the control group. ConclusionFemale sex assignment seems legitimate according to this study and the development of gender identity in these patients matches the sex assigned at birth. Resolving early on the adequacy of the genital anatomy with the sex assigned is promoted by patients as well as their parents. Proper psychomotor development and sexual satisfaction underline the absence of complications related to the surgical technique and the relevance of early surgical management.

Evaluation of a psychosocial education program for families with congenital adrenal hyperplasia

Congenital Adrenal Hyperplasia (CAH) is an inherited condition caused by an enzyme deficiency which leads to a potentially life threatening adrenal crisis. Poor compliance and any illness, injury, or major medical procedure can be life threatening. Medical interventions, counselling and timely education are essential for these families. This study evaluated a psychosocial education program (PEP) developed to meet the needs of families with a child with CAH, with the additional opportunity of exploring the impact of CAH on the child and family. Two hundred and two participants (parents/carers/ children with CAH and siblings), from 68 families took part in the study. Participants attended a full-day workshop which included information about CAH, a practical injection session, group discussions and provision of a resource folder. Data were collected to explore the impact of CAH on the child and family using the Child Behaviour Checklist (CBCL) and the Child Health Questionnaire (CHQ). Sibling data were collected for comparison of the CAH group with siblings and population norms. Evaluation of the PEP involved baseline and follow-up (immediate, six months and 12 months post education) measures of knowledge using the CAH Knowledge Assessment Questionnaire (CAHKAQ) and a formal evaluation. Evaluation of the PEP showed that knowledge increased immediately following the PEP, which was maintained over time. Sick day management was seen to be the major challenge for families. Fathers’ and Mothers’ scores for behaviour (CAH group compared to siblings) were within population norms, although Father’s rated children with CAH, having lower social competence than siblings and norms. Fathers’ and Mothers’ were in agreement about the impact of CAH, with ratings lower than siblings and population norms for bodily pain & discomfort, general health of the child, and emotional impact on parents. The PEP achieved its major goal of increasing knowledge about CAH, and was positively evaluated by families. The workshop has now been incorporated into a DVD that is available to families and health professionals.

High Incidence of Abnormal Circadian Blood Pressure Profiles in Patients on Steroid Replacement Therapy due to Secondary Adrenal Insufficiency and Congenital Adrenal Hyperplasia without Overt Hypertension - Initial Results

Patients on steroid replacement therapy are at an increased risk of cardiovascular complications owing to the fact that disruptions in the cortisol diurnal rhythm may affect the blood pressure (BP) profile. Aim: To evaluate the circadian BP profiles of patients with secondary adrenal insufficiency (SAI) and congenital adrenal hyperplasia (CAH) on steroid replacement therapy and to compare BP profiles of patients receiving hydrocortisone (HC) in different dosing schedules. Methods: The study included 33 patients: 15 SAI and 18 CAH (mean age 13.2 years 95CI 11.3-15.1). There were no patients with previously diagnosed overt hypertension. Patients with SAI received a mean of 7.39 mg/m2 of HC in 3 daily doses (in the morning (M) 50%, in the afternoon (A) 25%, in the evening (E) 25%), CAH patients 17.9 mg/m2 of HC in the following dosing schedules: 5 patients in 3 equal doses, 7 patients received M: 40% A: 40% E: 20%, the remaining 6 patients had the same dosing schedule as patients with SAI. Fludrocortisone (FC) was given to 13 patients with CAH in 2 equal daily doses. The total dose of HC/FC as well as the dosing schedule of HC was adjusted individually based on clinical and biochemical outcomes. Standard 24-hour BP monitoring (ABPM) was performed using an Ambulatory BP Monitor (Space labs 90217, USA). Results: The majority of the patients (almost 70% SAI, 80% CAH) presented with an abnormal 24-hour BP profile. There were no significant differences in ABPM results between SAI and CAH patients, and no differences between CAH patients treated with and without FC. There was no correlation between HC and FC doses [mg/m2] and ABPM results except that mean night SBP values increased with greater HC doses (r=0.51, p<0.05). Among the CAH group the highest percentage of abnormal ABPM results was observed in patients who received HC in doses: M: 50% A: 25% and E: 25%, the most favorable BP profile was observed in patients with dosing schedule: M: 40%, A: 40%, E: 20%.However there were no significant differences between patients with different treatment protocols, the results suggest that observed disruptions of the BP profile could be related to the HC dosing schedule. Conclusions: The incidence of abnormal BP profiles in patients on steroid replacement therapy due to SAI and CAH without overt hypertension is high. The disruptions of the BP profiles are not associated with the dose of HC or FC. The abnormal BP profiles in patients with SAI or CAH may be related to the HC dosing schedule. 24-hour ABPM seems to be a useful, non-invasive and safe method for the monitoring of HC and FC replacement therapy in patients with adrenal insufficiency. Further investigations in the larger groups of patients are needed.