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Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements., (© 2024 Wiley Periodicals LLC.)

Objective: This study aimed to analyze if anthropometric factors and physical appearance are associated to QoL in Turner syndrome (TS)., Materials and Methods: Observational, analytical, and cross-sectional study. The SF-36 was applied along with an additional questionnaire regarding specific characteristics of TS., Results: There were no differences in quality of life (QoL) in TS women regarding median height and appropriate height according to parental target height, however, participants satisfied and who did not desire to change their height had better scores in the mental health and role emotional domains than those not satisfied and desired to change it. When comparing participants who were or were not bothered by physical appearance, the results showed that those not bothered by physical appearance had a better score in the vitality and social function domains. Considering patients who did or did not desire to change physical appearance, those who did not want to change their physical appearance had higher scores in the mental component and in the social function and mental health domains of the SF-36., Conclusion: This study indicated that anthropometric factors and physical appearance may possibly be associated to QoL in TS, and also emphasizes the need to develop and validate an official questionnaire regarding specific TS characteristics in order to assess in more detail how specific characteristics of TS interfere with their QoL.

Objective: Herein, we compared ambulatory blood pressure (ABP) between young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency and a control group. Additionally, we analyzed correlations between the glucocorticoid dose and androgen levels and ABP parameters., Subjects and Methods: This case-control study included 18 patients (6 males and 12 females) and 19 controls (8 males and 11 females) matched by age (18-31 years). ABP monitoring was used to estimate blood pressure (BP) over a 24-h period., Results: No difference was noted between patients and controls in terms of systolic BP (males, 115.5 ± 5.6 vs. 117.0 ± 9.3, P = 0.733; and females, 106.4 ± 7.9 vs. 108.4 ± 7.6, P = 0.556, respectively) and diastolic BP during 24 h (males, 62.8 ± 7.5 vs. 66.2 ± 5.6, P = 0.349; and females, 62.7 ± 4.9 vs. 62.3 ± 4.9, P = 0.818, respectively). Systolic and diastolic BP and pulse pressure during daytime and nocturnal periods were similar between patients and controls. Furthermore, no differences were detected in the percentage of load and impaired nocturnal dipping of systolic and diastolic BP between patients and controls during the 24-h period. Additionally, the glucocorticoid dose (varying between r = -0.24 to 0.13, P > 0.05) and androgens levels (varying between r = 0.01 to 0.14, P > 0.05) were not associated with ABP parameters., Conclusion: No signs of an elevated risk for hypertension were observed based on ABP monitoring in young adults with CAH attributed to 21OHase deficiency undergoing glucocorticoid replacement therapy.

Background: Males have higher weight and length at birth than females., Aim: To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD)., Subjects and Methods: A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated., Results: Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age., Conclusions: The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

It is of great importance to investigate any potential detrimental effect on bone health in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy. This study demonstrated normal bone health in well-controlled patients. Additionally, glucocorticoid dose may play an important role in the mineral density of femoral neck region., Purpose: To compare regional bone mineral densities (BMDs) and bone statuses of young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency with a control group. The duration and dose of glucocorticoid therapy and relative skeletal muscle index (an indicator of sarcopenia) were also analyzed as parameters to predict bone health., Methods: This case-control study included 23 patients (7 male and 16 female) and 20 controls (8 male and 12 female) matched by age range (18 to 31 years). Dual energy X-ray absorptiometry and phalangeal quantitative ultrasound (QUS) were used to estimate BMD and bone status, respectively., Results: No difference was observed between patients and controls (of both sexes) in absolute values of BMD and Z-scores for the total body, lumbar spine, and femoral neck; or the bone status (estimated by phalangeal QUS). Multiple linear regression analysis demonstrated that relative skeletal muscle index independently correlated with BMD of the entire body (β: 0.67, P = 0.007), the lumbar spine (β: 0.73, P = 0.005), and the femoral neck (β: 0.67, P = 0.007). However, the dose of glucocorticoids (β: - 0.38, P = 0.028) independently correlated with BMD in the femoral neck region alone., Conclusion: No signs of change in bone health were observed in patients with CAH when compared to the reference group. Additionally, a marker of sarcopenia was demonstrated to have a role in mineral density mechanisms in all analyzed bone sites. Only the femoral neck BMD seemed to be significantly dependent on glucocorticoid dose., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: The association of congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase enzyme (21OHase) deficiency, duration of treatment and dosage with cardiovascular dysfunction in young adults remains unclear. We aimed to evaluate myocardial function, vascular structures and epicardial fat thickness in young adults with CAH as a result of 21OHase deficiency. Correlations between the duration and dose of glucocorticoid therapy and cardiovascular parameters were analysed., Methods: This case-control study of young adults (18-31 years old) included 20 patients (5 men and 15 women) and 16 control subjects (8 men and 8 women). Echocardiographic analysis was performed using high-resolution ultrasound., Results: No ultrasonographic changes in any indices of myocardial function, vascular structures and epicardial fat thickness were found in patients, except for an impaired left ventricular end-diastolic diameter in female patients (28.1 ± 1.6 vs 26.0 ± 2.4 mm/m 2 , P = .021), compared with those in individuals in the control group. Nevertheless, the individual patient values were within the normal range. Multiple linear regression analysis in female patients demonstrated that an elevated daily dose of glucocorticoids correlated with increased indices of left ventricular posterior wall thickness (Partial r = 0.68, P = .007), left ventricular end-diastolic diameter (Partial r = 0.62, P = .017), aortic diameter (Partial r = 0.60, P = .022) and left carotid artery intima-media thickness (Partial r = 0.61, P = .021), independently of treatment duration., Conclusion: No signs of cardiovascular dysfunction were observed in any patient. The daily dose of glucocorticoids may play a role in the mechanisms of some markers of cardiac hypertrophy, left ventricular and aortic dilation and subclinical atherosclerosis., (© 2021 John Wiley & Sons Ltd.)

Context: Congenital adrenal hyperplasia (CAH) patients have potential normal longevity. However, a greater risk for cardiovascular disease has been reported. Insulin resistance and hyperinsulinemia have been described in CAH patients, whereas the prevalence of overt type 2 diabetes is not higher in CAH than in normal population., Objective: To examine the contributions of insulin secretion and of hepatic insulin clearance to compensatory hyperinsulinemia in young insulin-resistant adults with classic CAH due to 21-hydroxylase deficiency (21-OHD)., Design: Cross-sectional., Setting: University outpatient clinics., Methods: Fifty-one participants: 21 controls, and 30 CAH (15 virilizing and 15 salt-wasting phenotypes), female/male (33/18), age (mean [SD]): 24.0 (3.6) years, body mass index: 24.6 (4.9)kg/m2 with normal glucose tolerance, were submitted to a hyperglycemic clamp study., Main Outcome Measures: Insulin sensitivity, beta cell function, and hepatic insulin clearance using appropriate modeling., Results: We found an increased insulin resistance in 21-OHD. The systemic hyperinsulinemia (posthepatic insulin delivery) was elevated in CAH patients. No increases were observed in insulin secretory rate (beta cell function) in the first phase or during the hyperglycemic clamp. The increase in insulin concentrations was totally due to a ~33% reduction in insulin clearance., Conclusion: 21-OHD nonobese subjects have reduced insulin sensitivity and beta cell response unable to compensate for the insulin resistance, probably due to overexposure to glucocorticoids. Compensatory hyperinsulinemia is most related with reduced hepatic insulin clearance. The exclusive adaptation of the liver acts as a gating mechanism to regulate the access of insulin to insulin-sensitive tissues to maintain glucose homeostasis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case-control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18-31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m 2 , p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m 2 , p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m 2 , p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m 2 , p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m 2 , p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m 2 , p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = -0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms., (© 2020 AOCS.)

Objective: To characterize resting energy expenditure (REE) in patients with classic 21-hydroxylase congenital adrenal hyperplasia (21-OH CAH) using indirect calorimetry and compare it to the most commonly used REE predictive equations. Methods: This case-control study comprised 29 post-pubertal 21-OH CAH patients regularly followed at the University of Campinas. Elevated serum 17-hydroxyprogesterone and CYP21 gene molecular analysis confirmed the diagnosis. A healthy control group paired by age, gender, and body mass index was examined. Dual-energy X-ray absorptiometry (DEXA) measured body compositions. A bioimpedance analyzer determined fat-free mass, and indirect calorimetry using a metabolic cart measured REE. Results: Unlike our initial hypothesis, REE was similar between the groups (18.7 ± 3.1 kcal/kg/day in CAH vs. 20.3 ± 3.5 kcal/kg/day in controls; P = .728). No predictive equations reached the stipulated accuracy criteria, thus lacking validity in REE assessment in adults with the characteristics of the group studied. DEXA analysis revealed higher body fat and diminished nonbone lean mass in 21-OH CAH. Anthropometric and bioelectrical impedance parameters were not significantly different. Conclusion: Classic 21-OH CAH is generally followed in reference centers, which may facilitate indirect calorimetry use for REE measurement. Alternatively, considering our REE findings in adult 21-OH CAH patients, nutrition management based on 25 kcal/body weight/day (measured REE × activity factor 1.2 to 1.3) may be reasonable for current body weight maintenance in these patients. Abbreviations: 17-OHP = 17-hydroxyprogesterone; 21-OH CAH = classic 21-hydroxylase deficiency congenital adrenal hyperplasia; BMI = body mass index; REE = resting energy expenditure; VO2 = volume of oxygen; VCO 2 = volume of carbon dioxide.

Current literature presents no consensus regarding which aspects influence health-related quality of life (HRQoL) of women with Turner syndrome (TS). The objective of the present study was to compare HRQoL in the TS and control group, using components and domains of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Observational, descriptive, and cross-sectional study with 44 women with TS aged between 18 and 30 years (TS group) and 44 healthy women of the same age which were sisters, relatives, or friends of the TS group (control group). A registration form and the SF-36 questionnaire were used to analyze HRQoL in TS in relation to the control group. The TS group presented better scores in the mental component summary and in the role physical, bodily pain, general health, social function, and role emotional domains compared to the control group. This study presented some unexpected results, different from those found in the current literature, showing the possibility of TS patients presenting better coping strategies. It is necessary to develop a specific questionnaire to assess QoL in TS and analyze in great detail which factors may influence the HRQoL of these patients., (© 2019 Wiley Periodicals, Inc.)

Purpose: This study aimed to systematically review the available literature on "quality of life" (QoL) or "health-related quality of life" (HRQoL) in Turner syndrome (TS) patients and to analyze the relations among height, puberty, and the use of growth hormone (GH) and the QoL of TS patients., Methods: An electronic bibliographic search was conducted through the PubMed, Embase, Bireme, Scopus, and Web of Science databases. The main terms were "Quality of Life" and "Turner syndrome.", Results: Among the databases, 559 articles were found; after the selection process, 13 studies were selected. A quality assessment was conducted, and all the studies were of high quality. Eight well-known QoL questionnaires were used, and the selected studies presented factors that may be related to the QoL of TS patients, such as height, puberty, and GH use. However, a more detailed understanding of which factors are associated with the QoL of TS patients is still needed, which may be due to the lack of specific QoL instruments involving important aspects related to TS., Conclusion: The QoL of TS patients appears to be compromised, but existing data regarding the relations among height, puberty, and GH and QoL are still controversial. Although these factors should be carefully considered in TS patients, it was not possible to determine whether they have a significant relation with the QoL of TS patients.

Background: Ultrasensitive assays to measure pre-pubertal gonadotropins levels could help identify patients with Turner syndrome (TS) in mid-childhood, but studies in this field are scarce. The aim of this study was to analyze gonadotropins levels in girls with TS throughout childhood., Methods: Retrospective longitudinal study conducted with 15 girls with TS diagnosed with < 5 years whose FSH and LH measures were available since then. Hormones were evaluated in newborn/mini-puberty (< 0.5 years), early childhood (0.5-5 years), mid-childhood (5-10 years) and late childhood/adolescence (> 10 years). In newborn/mini-puberty and late childhood/adolescence pre-pubertal or pubertal gonadotropins were considered normal; in early childhood and mid-childhood concentrations above the pre-pubertal range were considered abnormal., Results: Abnormally high FSH alone was found in four of five patients in newborn/mini-puberty, 13 of 15 during early childhood and nine of 15 during mid-childhood. In the group of 12 patients in late childhood/adolescence, the three girls with spontaneous puberty had only normal levels; the remaining showed only post-menopausal concentrations. In mid-childhood one patient exhibited only pre-pubertal FSH. Conversely, most LH measurements in early and mid-childhood were normal., Conclusion: Karyotyping of girls with short stature and high FSH levels would allow early diagnosis of Turner syndrome in a significant number of patients, particularly when resources for chromosome study of all girls with growth deficiency are limited.