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OBJECTIVE: To investigate potential differences in pregnancy, delivery, and neonatal outcomes between 2 hyperandrogenic conditions in reproductive-aged women: polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH). DESIGN: Retrospective population-based study with data from the Health Care Cost and Utilization Project-Nationwide Inpatient Sample Database from 2004-2014. SETTING: Not applicable. PATIENT(S): A total of 14,881 women with PCOS and 298 women with CAH. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Gestational diabetes mellitus, placenta previa, pregnancy-induced hypertension (HTN), gestational HTN, preeclampsia, eclampsia, preeclampsia and eclampsia superimposed on HTN, preterm birth, preterm premature rupture of membrane, abruptio placenta, chorioamnionitis, mode of delivery, maternal infection, hysterectomy, blood transfusion, venous thromboembolism (deep vein thrombosis and pulmonary embolism during pregnancy, intrapartum, or postpartum), maternal death, chorioamnionitis, septicemia during labor, postpartum endometritis, septic pelvic, peritonitis, small for gestational age, congenital anomalies, and intrauterine fetal demise. RESULT(S): After adjusting for potential confounders, we found that women with PCOS were at increased risk of developing pregnancy-induced HTN (adjusted odds ratio [OR] = 1.76; 95% confidence interval [CI]: 1.12-2.77) and gestational diabetes (adjusted OR = 1.68; 95% CI: 1.12-2.52) when compared with women with CAH. Contrary women with CAH were at increased risk for delivery via cesarean section (adjusted OR = 0.59; 95% CI: 0.44-0.80) and small for gestational age neonates (adjusted OR = 0.32; 95% CI: 0.20-0.52). CONCLUSION(S): To our knowledge, this study is the first to directly compare obstetric and neonatal outcomes between patients with PCOS and CAH. Despite the similar phenotypes and some common hormonal and biochemical profiles, such as insulin resistance, hyperinsulinemia, and hyperandrogenism, our results suggest the existence of additional metabolic pathways implicated in the pathogenesis of pregnancy complications.
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Hiperplasia Suprarrenal Congênita , Síndrome do Ovário Policístico , Resultado da Gravidez , Humanos , Feminino , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Gravidez , Estudos Retrospectivos , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/epidemiologia , Adulto , Recém-Nascido , Resultado da Gravidez/epidemiologia , Complicações na Gravidez/epidemiologia , Bases de Dados Factuais , Adulto JovemRESUMO
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Hiperplasia Suprarrenal Congênita , Humanos , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/epidemiologia , Feminino , Masculino , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , EndocrinologiaRESUMO
PURPOSE: Congenital Adrenal Hyperplasia (CAH) is one of the highly prevalent autosomal recessive endocrine disorders. The majority of CAH cases result from mutations in the CYP21A2 gene, leading to 21-hydroxylase deficiency. However, with the pseudogene-associated challenges in CYP21A2 gene analysis, routine genetic diagnostics and carrier screening in CAH are not a part of the first-tier investigations in a clinical setting. Furthermore, there is a lack of data on the carrier frequency for 21-OH deficiency. Therefore, this study is aimed at investigating the carrier frequency of common pseudogene derived CYP21A2 mutations in Southern India. METHODS: Recently, a cost-effective Allele-specific PCR based genotyping for CYP21A2 hotspot mutations has been demonstrated to be a highly specific and sensitive assay at the authors' center. Leveraging this approach, a total of 1034 healthy individuals from South India underwent screening to identify the carrier frequency of nine hotspot mutations in the CYP21A2 gene. RESULTS: In this study, it was observed that 9.76% of the subjects were carriers for one or more of the nine different CYP21A2 mutations. Among the carriers, the most common was the large 30 kb deletion, followed by II72N, E6 CLUS, and I2G mutations. CONCLUSION: We have identified a high prevalence of CYP21A2 mutation carriers in Southern India. These findings emphasize the importance of implementing and expanding cost-effective genetic diagnostics and carrier screening throughout India. Such initiatives would play a crucial role in managing the disease burden, enabling early intervention, and establishing guidelines for CAH newborn genetic screening in the country. This study represents the first carrier screening data on CYP21A2 hotspot mutations from India and is the largest study conducted till date in this context.
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Hiperplasia Suprarrenal Congênita , Testes Genéticos , Mutação , Esteroide 21-Hidroxilase , Humanos , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Índia/epidemiologia , Feminino , Testes Genéticos/métodos , Testes Genéticos/economia , Masculino , Heterozigoto , Frequência do Gene , Adulto , Triagem de Portadores Genéticos/métodos , Adulto JovemRESUMO
PURPOSE: To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease. METHODS: This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed. RESULTS: The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0-25.1) ng/mL; T1: 7.1 (1.8-19.9) ng/mL; T2: 5.9 (2.0-20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3-2.5) ng/mL; T1: 0.3 (0.3-1.1) ng/mL; T2: 0.5 (0.3-1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis. CONCLUSIONS: our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.
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17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congênita , Nefrolitíase , Humanos , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/epidemiologia , Masculino , Feminino , Criança , Nefrolitíase/epidemiologia , Nefrolitíase/sangue , Nefrolitíase/etiologia , Estudos Prospectivos , Pré-Escolar , 17-alfa-Hidroxiprogesterona/sangue , Incidência , Adolescente , Hormônio Adrenocorticotrópico/sangue , Sulfato de Desidroepiandrosterona/sangue , Lactente , Androstenodiona/sangue , Ultrassonografia , Fatores de RiscoRESUMO
INTRODUCTION: We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population. MATERIAL AND METHODS: The study included 304 premenopausal women referred to our clinic for oligomenorrhoea. Anthropometric measurements and Ferriman-Gallwey score were evaluated, and thyroid hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, dehydroepiandrosterone sulphate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels were measured in all patients. If basal 17-OHP was > 2 ng/mL, we evaluated adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels. CS was screened by 1 mg-dexamethasone suppression test, and if the cortisol value was > 1.8 µg/dL, we performed additional confirmatory tests, and if necessary, pituitary magnetic resonance imaging (MRI) and inferior petrosal sinus sampling (IPSS) were performed. RESULTS: The most common cause of oligomenorrhoea was polycystic ovary syndrome (PCOS) that was detected in 81.57% of cases, followed by hyperprolactinemia at 7.23% and hypothalamic anovulation at 5.26%. The prevalence of premature ovarian failure (POF) was 1.6%, and non-classical congenital adrenal hyperplasia (NCAH) was 1.97%. CS was detected in 7 (2.30%) patients. All the patients with CS were found to have Cushing's disease (CD). Although 3 patients with CD had classical signs and symptoms, 4 had none. Patients with CD had similar total testosterone values to those in the PCOS and NCAH groups, but they had significantly higher DHEA-S compared to both groups (CD vs. PCOS, p = 0.001 and CD vs. NCAH, p = 0.030). CONCLUSIONS: We found higher prevalence of CS in patients with oligomenorrhoea even in the absence of clinical signs. Therefore, we suggest routine screening for CS during the evaluation of patients with oligomenorrhoea and/or PCOS. The likelihood of CS is greater in patients with high androgen, especially DHEA-S levels.
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Hiperplasia Suprarrenal Congênita , Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Oligomenorreia/epidemiologia , Prevalência , Síndrome de Cushing/diagnóstico , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/epidemiologia , Testosterona , DesidroepiandrosteronaRESUMO
Context: Patients with primary adrenal insufficiency due to congenital adrenal hyperplasia (CAH) are at risk for adrenal crisis during infectious illnesses. Increased risk of infection including COVID-19 has been variably reported. Objective: To evaluate COVID-19 illness outcomes and stress dose practices in a large cohort of patients with CAH during the first two years of the pandemic and compare observations of COVID-19 infection in patients with CAH to the general USA population. Methods: Between March 2020 and November 2022, patients with CAH followed at the National Institutes of Health Clinical Center were queried about COVID-19 infection during their routine visits. Cases of COVID-19 were compared to controls. COVID-19 infection rates and symptoms were compared to general USA population data from the Centers for Disease Control and Prevention. Results: Of 168 patient visits, there were 54 (32%) cases of COVID-19 infection, and 15 (28%) were pediatric. Overall an association was found between acquiring COVID-19 and obesity (p=0.018), and adults acquiring COVID-19 were on lower doses of fludrocortisone (p=0.008). Fewer cases of COVID-19 infection were reported in those receiving hydrocortisone or modified-release hydrocortisone compared to longer acting glucocorticoids (p=0.0018). In our CAH population, the pattern of COVID-19 infection rates and COVID-related symptomatology were similar to those observed in the general USA population. Most patients with the presumed alpha variant reported anosmia and ageusia, while gastrointestinal symptoms were commonly reported during the delta and omicron waves. Stress dosing occurred in 30/54 cases, and 7 received parenteral hydrocortisone. Two hospitalizations occurred; one pediatric and one adult, both with co-morbidities. There were 5 emergency room visits and no reported deaths. Conclusion: Patients with CAH with close follow-up do not appear to be at increased risk of acquiring COVID-19 or to have a more severe course of COVID-19 compared to the general USA population. Obesity may increase risk of acquiring COVID-19 in patients with CAH, and overall infection risk may be lower in those receiving short-acting and circadian glucocorticoid replacement therapy. Established age-appropriate guidelines for stress dosing during infectious illnesses should be used for patients with CAH and COVID-19. COVID-19 specific guidelines are not indicated. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT00250159.
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Hiperplasia Suprarrenal Congênita , COVID-19 , Adulto , Criança , Humanos , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , Glucocorticoides/uso terapêutico , Hidrocortisona/uso terapêutico , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/tratamento farmacológico , SARS-CoV-2 , Estados Unidos , Estudos de Casos e ControlesRESUMO
INTRODUCTION: Testicular adrenal rest tumors (TART) are common in males suffering from congenital adrenal hyperplasia (CAH). Correct and timely diagnosis is important for differential diagnosis with malignant testis tumors, related infertility and as TART may worsen in time, especially in the absence of adequate and continuous hormonal control. The rarity of the disease, predominance of small cohorts and case reports and research heterogeneity (concerning type of CAH, patients' age and specific focus of the paper) complicate the understanding of this condition. OBJECTIVES: To review epidemiological and clinical aspects of TART, including treatment and prognosis. METHODS: Non-systematic review of CAH-related TART research. RESULTS: TART's prevalence grows progressively over time, predominating after puberty, affecting a mean of 20-40 % of CAH males. There is no proof of more frequent proportional affection of specific CAH phenotypes or types of enzyme deficiency, but cases of TART among non-classic CAH patients have been rarely reported. Chronic undertreated are more frequently affected and present larger tumors. Systematic ultrasound screening of CAH males is the state-of-the art for diagnosis, but TART are still often diagnosed in CAH adults seeking infertility treatment. TART are usually asymptomatic and present normal testicular volume. Biopsies are not recommended, except when the differential diagnosis between TART and testicular tumors cannot be guaranteed. Abnormal semen analysis is common. Leydig cell tumors are the main differential diagnosis, due to histological similarities to TART. Misdiagnosis may lead to unnecessary orchiectomies. Preservation of gonadal functions is inversely proportional to the total tumor volume. Tumors tend to regress under adequate adrenal suppression with steroids. Surgery in not indicated to treat TART. DISCUSSION: The reported prevalence of TART depends on age, usage of systematic follow-up ultrasound, and adequate CAH control. Timely detection of the disease is important to avoid irreversible gonadal dysfunction (not clinically apparent, due to high serum levels of androgen) and infertility. The relationship between TART and specific CAH phenotypes/genotypes has not been proved, and some cases do not present abnormal serum ACTH levels. Knowledge about TART should be disseminated among non-experts, to avoid unnecessary orchiectomies and false diagnosis of malignant testis tumors. Infertility is frequent, but has not been not satisfactorily addressed by physicians, even among experts. Sperm cryopreservation should be early offered to CAH adult males, but there are offer problems related to high cost.
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Hiperplasia Suprarrenal Congênita , Tumor de Resto Suprarrenal , Infertilidade , Neoplasias Testiculares , Adulto , Humanos , Masculino , Tumor de Resto Suprarrenal/diagnóstico , Tumor de Resto Suprarrenal/epidemiologia , Tumor de Resto Suprarrenal/etiologia , Sêmen , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/terapiaRESUMO
CONTEXT: The prevalence of cardiovascular and metabolic complications among adults with 21-hydroxylase deficiency (21OHD) is unknown. OBJECTIVE: We sought to determine the prevalence of cardiovascular and metabolic morbidities among adults with 21OHD and to identify clinical factors and biomarkers associated with cardiovascular outcomes. METHODS: A 10-year retrospective cross-sectional analysis was conducted on adult patients with confirmed 21OHD, aged 18 to 70 years, who had at least one clinical visit for assessment at the University of Michigan. The presence of cardiovascular diseases (CVDs) and other metabolic comorbidities was extracted from medical records based on International Classification of Diseases (ICD) codes. Medical treatments, glucocorticoid (GC) and mineralocorticoid doses, as well as specific biomarkers of disease control since age 18, were collected for analysis. RESULTS: A total of 254 patients with 21OHD, median age of 35 years (interquartile range, 28.25-46 y), were included in the analysis. The prevalence of CVDs in the entire cohort was 7.5%. An increase in prevalence was seen from early adulthood, reaching 25% in patients older than 60 years. Increasing age (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.09), hypertension (OR, 4.27; 95% CI, 1.41-12.92), and higher GC doses (OR, 1.51; 95% CI, 1.11-2.06) were significantly associated with prevalent CVDs. Higher plasma renin activity was significantly associated with CVDs (OR, 1.07; 95% CI, 1.01-1.15) but not other biochemical markers of disease. CONCLUSION: Cardiometabolic morbidities are prevalent among adults with 21OHD. Hypertension, age, and GC exposure are the main predictive factors of established CVDs in our cohort.
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Hiperplasia Suprarrenal Congênita , Doenças Cardiovasculares , Hipertensão , Adulto , Humanos , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Glucocorticoides , Hipertensão/complicações , Biomarcadores , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Esteroide 21-HidroxilaseRESUMO
Sex differences in the psychological impact of the COVID-19 pandemic have been consistently reported, showing disproportionally high rates of anxiety/distress in women relative to men. The mechanisms underlying this sexual dimorphism remain unclear. The present study queries the potential protective role of early hyperandrogenism on brain development. A natural model of sex-steroids abnormality, classic congenital adrenal hyperplasia (CAH), was used to test this question. CAH is characterized by adrenal androgen overproduction in utero (prenatal) through the neonatal critical developmental period. An online survey collected information on subjective responses to the COVID-19 pandemic. Matched on demographic variables, 60 adults carrying a diagnosis of classic CAH and 240 adults from the general population (non-CAH) were compared on levels of anxiety/distress in the first year of the COVID-19 pandemic (May 2020-April 2021). Structural Equation Modeling was used to test the modulation by CAH status of Sex effects on anxiety/distress. Results revealed lower levels of anxiety/distress in the female CAH group compared to the other 3 groups (male CAH, female non-CAH, and male non-CAH). This finding suggests that pre-neonatal hyperandrogenism might impact the development of neural circuits underlying anxiety processes, in a way that enhances resilience to chronic stress.
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Hiperplasia Suprarrenal Congênita , COVID-19 , Hiperandrogenismo , Adulto , Recém-Nascido , Gravidez , Humanos , Feminino , Masculino , Caracteres Sexuais , Pandemias , Hiperandrogenismo/epidemiologia , Hiperandrogenismo/psicologia , COVID-19/epidemiologia , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/psicologia , Ansiedade/epidemiologia , Hormônios Esteroides Gonadais , EsteroidesRESUMO
INTRODUCTION: There are increased calls to address psychosocial needs among individuals with classical congenital adrenal hyperplasia (CAH). However, cross-cultural disparities exist in treatment practices and psychosocial outcomes that impact the generalizability of evidence-based recommendations. To date, this disparity has not been quantified. The present scoping review uses a dual approach to contrast rates of CAH diagnosis with CAH psychosocial research rates across countries. METHODS: Six electronic database searches were conducted for: (1) CAH incidence/birth/prevalence rates; and (2) psychosocial research with affected individuals and their families. Two authors reviewed each abstract for inclusion criteria. RESULTS: Sixty-eight and 93 full-text articles, respectively, were evaluated for incidence and country. The countries/regions with the highest reported CAH rates are Thailand, Ghana, and India. Those with the greatest portion of psychosocial publications are the USA, Germany, and the UK. CONCLUSION: A discrepancy exists between those countries with the highest CAH rates and those publishing psychosocial research. Specifically, increased rates of CAH are seen in non-Western countries/regions, whereas most psychosocial research arises out of Western Europe and the USA. Due to cultural differences between these regions, increased global collaboration is needed to both inform psychosocial research and translate findings in ways that are representative worldwide.
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Hiperplasia Suprarrenal Congênita , Humanos , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/diagnóstico , Comparação Transcultural , Alemanha , Incidência , Europa (Continente)RESUMO
BACKGROUND: Hyperandrogenism and supraphysiologic glucocorticoid replacement may lead to subclinical atherosclerosis in people with congenital adrenal hyperplasia (CAH) and predispose the development of cardiovascular diseases from an early age. OBJECTIVES: To determine if cardiometabolic risk factors and subclinical atherosclerosis are more frequent in patients with CAH due to 21-hydroxylase deficiency (21OHD) and if there is an association with clinical, hormonal and treatment of 21OHD. MATERIAL AND METHODS: A descriptive prospective cross-sectional study exploring clinical variables, biochemical, hormonal variables, endothelial dysfunction (flow-mediated dilation < 5%) and carotid intima media thickness (≥ 95 percentile in adolescents and ≥ 75 percentile in adults) and epicardial fat. Adolescents and young patients with 21OHD were compared with controls matched by age, sex, body mass index and Tanner stage. RESULTS: Forty four subjects (22 with CAH), 36 (82%) females, with a mean age of 17.1 ± 5.5 years (range 10-30 years) were included. Family history revealed diabetes, hypertension, and hypercholesterolemia with high frequencies in both groups. The blood pressure was similar in both groups. Blood glucose levels were lower and triglycerides higher in patient (both p < 0.01). Epicardial fat was similar between groups and in patients with CAH it was related to cholesterol levels ââ(r = 0.679, p < 0.01), time since CAH diagnosis (r = 0.462, p = 0.03) and glucocorticoid dose (r = 0.499, p = 0.04). Carotid intima media thickness (CIMT) had a tendency to be increased in patients (p = 0.07) and was directly related to 17-hydroxyprogesterone (r = 0.510, p = 0.018), diastolic blood pressure (r = 0.444, p = 0.04) and the homeostatic model assessment (HOMA) index (r = 0.507, p = 0.01). Endothelial dysfunction was not different between groups. CONCLUSIONS: Some cardiometabolic risk factors were increased in patients with CAH and were associated with clinical, hormonal and treatment parameters of CAH. Cardiometabolic risk should be evaluated regularly in patients with CAH.
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Hiperplasia Suprarrenal Congênita , Aterosclerose , Doenças Cardiovasculares , Feminino , Humanos , Adolescente , Adulto Jovem , Criança , Adulto , Masculino , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Espessura Intima-Media Carotídea , Glucocorticoides/uso terapêutico , Estudos Transversais , Estudos Prospectivos , Fatores de Risco , Fatores de Risco de Doenças CardíacasRESUMO
Background: Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of primary adrenal insufficiency. Objective: We investigated the prevalence of depressive and anxiety disorders and antidepressant prescriptions in two large healthcare databases of insured children, adolescents, and young adults with CAH in the United States. Methods: We conducted a retrospective cohort study using administrative data from October 2015 through December 2019 for individuals aged 4-25 years enrolled in employer-sponsored or Medicaid health plans. Results: Adjusting for age, the prevalence of depressive disorders [adjusted prevalence ratio (aPR) = 1.7, 95% confidence interval (CI): 1.4-2.0, p<0.001], anxiety disorders [aPR = 1.7, 95% CI: 1.4-1.9, p<0.001], and filled antidepressant prescriptions [aPR = 1.7, 95% CI: 1.4-2.0, p<0.001] was higher among privately insured youth with CAH as compared to their non-CAH peers. Prevalence estimates were also higher among publicly insured youth with CAH for depressive disorders [aPR = 2.3, 95% CI: 1.9-2.9, p<0.001], anxiety disorders [aPR = 2.0, 95% CI: 1.6-2.5, p<0.001], and filled antidepressant prescriptions [aPR = 2.5, 95% CI: 1.9-3.1, p<0.001] as compared to their non-CAH peers. Conclusions: The elevated prevalence of depressive and anxiety disorders and antidepressant prescriptions among youth with CAH suggests that screening for symptoms of depression and anxiety among this population might be warranted.
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Hiperplasia Suprarrenal Congênita , Estados Unidos/epidemiologia , Adolescente , Humanos , Criança , Adulto Jovem , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/epidemiologia , Sistema Hipotálamo-Hipofisário , Estudos Retrospectivos , Sistema Hipófise-Suprarrenal , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Antidepressivos/uso terapêutico , PrescriçõesRESUMO
Objective: Congenital adrenal hyperplasia (CAH) is an inherited condition in which individuals require multiple daily doses of medication and are at risk for life-threatening adrenal crisis. The chronic nature and severity of CAH place children at risk for psychiatric morbidity. The aim was to assess the degree of anxiety and depressive symptoms in children with CAH. Methods: A cross-sectional cohort study of children (7-17 years) with CAH and their caregivers were recruited between May and December 2021. Children with hypothyroidism (HT) and their caregivers served as unaffected controls. Validated mental health questionnaires [Children's Depression Inventory 2 Self Report-Short (CDI-2), Screen for Child Anxiety Related Disorders (SCARED), Patient Health Questionnaire modified for Adolescents (PHQ-A); self and proxy] were completed by participants at one clinic visit. Higher scores indicated greater symptoms of anxiety and depression. Results: A total of 60 children and 56 parents participated. Among the children 34 had CAH (68% female, mean age 11.41±2.5, CAH duration 8.5±4.1) and 26 had HT (73% female, mean age 12.7±2.9 years, HT duration 6.0±4.2 years). There was no increase in anxiety and depression symptoms in children with CAH compared to controls. In sub-analyses, children with CAH and controls reported a greater number of anxiety and depression symptoms than their caregivers on the SCARED and CDI-2, respectively. There was no association between adrenal control and the degree of anxiety or depression symptoms. Conclusion: Children with CAH do not have more symptoms of anxiety or depression compared to controls. Child and caregiver-proxy responses lack agreement, suggesting that children with CAH may continue to benefit from routine mental health evaluation, regardless of voiced caregiver concern.
Assuntos
Hiperplasia Suprarrenal Congênita , Adolescente , Criança , Humanos , Feminino , Masculino , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Estudos Transversais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologiaRESUMO
Objective: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the CYP21A2 gene. After a high prevalence of classic 21-OHD CAH in the Romani population was reported in the Republic of North Macedonia, we decided to estimate the prevalence of 21-OHD in Croatia and, if high, assess the possible causes and estimate the frequency of particular CYP21A2 variants. Design: Cross-sectional study. Methods: Data from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study. CYP21A2 genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing. Results: According to a survey conducted in 2017, Croatia had 22,500 Romani people and six of them had a salt-wasting (SW) form of 21-OHD. All were homozygous for the c.IVS2-13A/C-G pathological variant in intron 2 and descended from consanguineous families belonging to different Romani tribes. The calculated prevalence of 21-OHD in Croatian Romani is 1:3,750, while in the Croatian general population, it is 1:18,000. Three of the six Romani patients originated from two neighboring villages in North-western Croatia (Slavonia County), as well as the seventh patient who is of mixed Romani/Croatian descent and heterozygous for the c.IVS2-13A/C-G pathological variant (not included in the prevalence calculation). Conclusion: A high prevalence of SW 21-OHD in the Croatian Romani population caused by the homozygous cIVS2-13A/C-G pathological variant was found. In addition to isolation and consanguinity, other possible reasons could be the heterozygous advantage of the CYP21A2 gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II.
Assuntos
Hiperplasia Suprarrenal Congênita , Roma (Grupo Étnico) , Humanos , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/genética , Esteroide 21-Hidroxilase/genética , Croácia/epidemiologia , Prevalência , Estudos Transversais , GenótipoRESUMO
Background: Congenital adrenal hyperplasia (CAH) caused by 3ß-HSD deficiency is a rare form of congenital adrenal deficiency with an autosomal recessive type of inheritance. Previously we have demonstrated that a single nucleotide variant (SNV) p.Trp230* in the homozygous state is a frequent cause of CAH among the indigenous population of North Ossetia-Alania represented by Ossetians. Methods: Genotyping of the NM_000198.3:c.690G>A p.Trp230* variant was performed by Real-time PCR. 339 healthy individuals of Ossetian origin were included in the study. Allele frequencies, Fisher's confidence intervals (CI) were calculated using the WinPepi v. 11.65 software. Comparison of allele frequencies was performed with the z-score test for two proportions. Results: Eight heterozygous carriers of c.690G>A variant in HSD3B2 gene were detected in 339 samples investigated. The total allele frequency of p.Trp230* variant was 0.0118 (n=8/678, 95% CI=0.0051-0.0231). Accordingly, the heterozygous carrier rate was 0.0236 (n=8/339). The frequency of CAH caused by p.Trp230* variant in HSD3B2 in Ossetian population was 1:7183 or 13.9 per 100,000 (95% CI: 1:1874-1:38447 or 3-53 per 100,000). Conclusion: The results demonstrate high frequency of p.Trp230* variant in Ossetians, which is most likely attributed to a founder effect.
Assuntos
Hiperplasia Suprarrenal Congênita , Progesterona Redutase , Humanos , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/genética , Homozigoto , Progesterona Redutase/genéticaRESUMO
Objective: To analyze the mutational spectrum, clinical characteristics, genotype-phenotype correlations, testicular adrenal rests tumor prevalence, and role of neonatal screening in congenital adrenal hyperplasia (CAH) patients from Slovakia and Slovenia. Design and methods: Data were obtained from 104 patients with CAH registered in Slovak and Slovenian databases. Low-resolution genotyping was performed to detect the most common point mutations. To detect deletions, conversions, point mutations, or other sequence changes in the CYP21A2 gene, high-resolution genotyping was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C). Results: 64% of the individuals had the salt-wasting form (SW-CAH), 15% the simple virilizing form (SV-CAH), and 21% the non-classic (NC-CAH). CYP21A2 gene deletion/conversion and c.293-13A/C>G pathogenic variant accounted together for 55.5% of the affected alleles. In SV-CAH p.Ile172Asn was the most common pathogenic variant (28.13%), while in NC-CAH p.Val282Leu (33.33%), CYP21A2 gene deletion/conversion (21.43%), c.293-13A/C>G (14.29%), Pro30Leu (11.90%). The frequency of alleles with multiple pathogenic variants was higher in Slovenian patients (15.83% of all alleles). Severe genotypes (0 and A) correlated well with the expected phenotype (SW in 94.74% and 97.3%), while less severe genotypes (B and C) correlated weaklier (SV in 50% and NC in 70.8%). The median age of SW-CAH patients at the time of diagnosis was 6 days in Slovakia vs. 28.5 days in Slovenia (p=0.01). Most of the Slovak patients in the cohort were detected by NBS. (24 out of 29). TARTs were identified in 7 out of 24 male patients, of whom all (100%) had SW-CAH and all had poor hormonal control. The median age at the diagnosis of TARTs was 13 years. Conclusion: The study confirmed the importance of neonatal screening, especially in the speed of diagnosis of severe forms of CAH. The prediction of the 21-OH deficiency phenotype was reasonably good in the case of severe pathogenic variants, but less reliable in the case of milder pathogenic variants, which is consistent compared to data from other populations. Screening for TARTs should be realized in all male patients with CAH, since there is possible remission when identified early.
Assuntos
Hiperplasia Suprarrenal Congênita , Tumor de Resto Suprarrenal , Neoplasias Testiculares , Humanos , Masculino , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Eslováquia/epidemiologia , Esteroide 21-Hidroxilase/genética , Tumor de Resto Suprarrenal/epidemiologia , Tumor de Resto Suprarrenal/genética , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/genéticaRESUMO
PURPOSE: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from enzyme deficiencies associated with steroidogenesis. The clinical presentation of non-classic CAH (NCAH) in females is often indistinguishable from other hyperandrogenic disorders like polycystic ovary syndrome (PCOS). The data on the prevalence of NCAH in unselected women in the literature is scanty. The research aimed to evaluate the prevalence of NCAH, carrier frequencies, and the correlation between clinical symptoms and genotype in Turkish women. METHODS: The study group comprised two hundred and seventy randomly-selected unrelated asymptomatic women of reproductive age (18-45). Subjects were recruited from female blood donors. All volunteers underwent clinical examination and hormone measurements. The protein-encoding exons and exon-intron boundaries of the CYP21A2, CYP11B1, HSD3ß2 and CYP21A2 promoter were sequenced by direct DNA sequencing. RESULTS: After genotyping, seven (2.2%) individuals were diagnosed with NCAH. The heterozygous carrier frequencies of CYP21A2, CYP21A2 promoter, CYP11B1, and HSD3ß2 genes with 34, 34, 41, and 1 pathologic mutation were determined at 12.6%, 12.6%, 15.2%, and 0.37% of volunteers, respectively. Gene-conversion (GC) frequencies between CYP21A2/CYP21A1P and CYP11B1/CYP11B2 were determined as 10.4% and 14.8%, respectively. CONCLUSION: Despite GC-derived higher mutation frequency determined in the CYP11B1 gene, the reason for the low frequency of NCAH due to 11OHD compared to 21OHD might be that gene-conversion arises with active CYP11B2 rather than an inactive pseudogene. HSD3ß1 exhibits high homology with HSD3ß2 located on the same chromosome; remarkably, it demonstrates low heterozygosity and no GC, most probably the outcome of a tissue-specific expression pattern.
Assuntos
Hiperplasia Suprarrenal Congênita , Esteroide 11-beta-Hidroxilase , Feminino , Humanos , Esteroide 11-beta-Hidroxilase/genética , Taxa de Mutação , Esteroide 21-Hidroxilase/genética , Citocromo P-450 CYP11B2/genética , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , MutaçãoRESUMO
PURPOSE: To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults. METHODS: A structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity. RESULTS: Of the 31 (67%) centres from 15 countries that completed the survey, 30 (97%) screened for hypertension by measuring blood pressure, 30 (97%) screened for obesity, 26 (84%) screened for abnormal glucose homoeostasis mainly by using Hb1Ac (73%), 25 (81%) screened for osteoporosis mainly by DXA (92%), 20 (65%) screened for hyperlipidaemia and 6 (19%) screened for additional CV disease. Of the 31 centres, 13 provided further information on the six co-morbidities in 244 patients with a median age of 33 yrs (range 19, 94). Of these, 126 (52%) were females and 174 (71%) received fludrocortisone in addition to glucocorticoids. Of the 244 adults, 73 (30%) were treated for at least one comorbidity and 15 (21%) for more than 2 co-morbidities. Of 73, the patients who were treated for osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity were 43 (59%), 17 (23%), 16 (22%), 10 (14%), 8 (11), 3 (4%) respectively. CONCLUSION: Cardiometabolic and bone morbidities are not uncommon in adults with CAH. There is a need to standardise the screening for these morbidities from early adulthood and to explore optimal therapy through routine collection of standardised data.
Assuntos
Hiperplasia Suprarrenal Congênita , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Hipertensão , Osteoporose , Feminino , Humanos , Adulto Jovem , Adulto , Masculino , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/diagnóstico , Obesidade/epidemiologia , Hipertensão/epidemiologia , Prevalência , Osteoporose/epidemiologia , Osteoporose/etiologiaRESUMO
The objective of the endeavour was to study the clinical presentation, diagnosis, and management of paediatric patients suffering from congenital adrenal hyperplasia and understand the issue in the light of available published data on the disease in Pakistan through a systematic analysis of researches. From an analysis of five-year retrospective data on congenital adrenal hyperplasia in patients of paediatric age group from a tertiary care centre in the capital of Pakistan and the available published Pakistani literature on CAH, it was concluded that the resultant deficiency of cortisol, aldosterone, and a rise in adrenal androgens is responsible for the symptomatology observed in the disease. Particularly, the presence of ambiguous genitalia makes the disease a difficult problem to tackle, especially in complex social conditions such as in Pakistan. The country not only lacks statistical data on the disease but also the diagnostic machinery making the problem two fold. It is only through maintaining an efficient disease registry and the introduction of neonatal screening programme that we might start grappling the crux of the issue.
Assuntos
Hiperplasia Suprarrenal Congênita , Transtornos do Desenvolvimento Sexual , Criança , Humanos , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Paquistão/epidemiologia , Estudos Retrospectivos , População do Sul da ÁsiaRESUMO
BACKGROUND: P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown. AIM: To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature. METHODS: The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated. RESULTS: Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants. CONCLUSION: This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.