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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.

Objective Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. Design This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. Methods Data were collected from 461 patients aged 0–18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits. Results The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0–14.5) mg/m2/day at age 1–8 years and the highest dose of 14.0 (11.6–17.4) mg/m2/day at age 12–18 years. Glucocorticoid doses decreased after 2010 in patients 0–8 years (P < 0.001) and remained unchanged in patients aged 8–18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. Conclusions Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.

Background Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. Methods Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. Results A total of 518 children—with a median of 11 children (range 1, 53) per center—had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P Conclusions The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency–related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.

Final height (FH) in congenital adrenal hyperplasia (CAH) patients is frequently under -1.5 SDS in relation to the normal population, even in those with good compliance, chronic androgen exposure or supraphysiological glucocorticoid doses could corroborate to this finding. Recombinant human growth hormone (GH) has been used as adjuvant therapy to improve FH in many disorders, but there are scarce data in CAH patients. Objective to analyze the effect of GH therapy on final height of CAH patients with compromised height prediction. Patients and Methods data of 26 patients (7F/19M) were retrospectively evaluated: 10 salt wasting-SW, 11 simple virilizing-SV and 5 with nonclassical form-NC. The SW patients were diagnosed at the neonatal period, SV and NC patients at mean chronological age of 3.6±2 and 7.2±3.8 yrs, respectively. All patients received cortisone acetate, hydrocortisone equivalent dose of 12.6±6.6 mg/m2/day in classical and 8.24±4.7 mg/m2/day in NC form; SW patients also received fludrocortisone 36±9.6mcg/m2/day. Near final height (NFH) was considered as BA of 13yrs for girls and 15yrs for boys; height and target height (TH) were described as SDS. All patients presented hormonal/molecular CAH diagnosis. The t test was used in the statistical analysis. Results Mean chronological and bone age (BA) at the beginning of GH therapy was 9.0±2.4 and 12.3±2yrs, respectively, mean duration of GH therapy was 4.1±1.9yrs and daily dose was 0.15 UI/kg/day. All patients were submitted to pubertal blockage with leuprorelin acetate 11.25 mg each 3 months during 3.9±1.1yrs or cyproterone acetate, mean dose 70±19 mg/m2/d during 4.7±2.5yrs. At the last evaluation, 19 patients (14M/5F) achieved FH: at the beginning of GH therapy mean H/BA in males was -2.1±0.38 and after -0.65±1 SDS (p0.05); the TH-FH was -0.6±1.2 SDS. Among females, mean H/BA at the beginning of GH therapy was -2.2±0.7 and after -0.84±0.9 SDS (p=0.01). Mean FH in females was 156±8 cm, mean TH was 160±5.8cm (p>0.05); the TH-FH was -0.6±0.7 SDS. Considering patients with FH and NFH, the FH-TH in males was 0.4±0.2 SDS and -0.15±0.9 SDS in females. An improvement of approximately 12.7cm in males and 12.4cm in females was observed. No patient presented hypertension and 7/26 patients presented insulin resistance, which normalized after GH withdrawal. Conclusion we observed that GH therapy associated with puberty blockers allowed the achievement of final height in the expected range of target height, without significant side effects. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

Testicular adrenal rest tumors (TARTs) are one of the most frequent comorbidities in males with 21-hydroxylase deficiency (CAH) and different prevalence rates have been reported. TART still present difficult control and frequently lead to infertility. Since it is also observed in patients with adequate hormonal control, its predictors factors are not yet well-known. Objective To evaluate TARTs prevalence in a significant CAH male cohort and to correlate with the long-term predictors and their impact on patients’ gonadal function. Patients and methods: Data of 53 males (24 salt wasters, 10 non-classical) were retrospectively evaluated. Hormonal control quality, assessed through long-term (last 5 years) mean ACTH, 17OHP, androstenedione (D4), testosterone (T), FSH, LH, inhibin B and renin levels were analyzed as well as sperm analysis. Mean glucocorticoid doses were evaluated and converted into cortisol equivalent. Genotypes, determined through entire CYP21A2 sequencing, were classified according to predicted impairment on residual enzymatic activity: null and severe groups. Data of patients with/without TARTs by scrotal ultrasound (US) were compared. Student's t and Chi-square tests were used. Results TARTs were observed in 18 (42%) of classical patients, all of them presented with bilateral lesions. None of the non-classical males presented with TART. The mean age of TART diagnosis was 21.32±5.2 years, the youngest patient with TART was 12y6mo old. Ten patients with TART underwent sperm analysis and all of them presented with altered results, while 3/10 patients without TART presented with abnormal sperm count. On the other hand, only 4 (22%) TART patients developed hypergonadotropic hypogonadism. Despite late diagnosis of the SV form in our cohort, the frequency of TARTs was significantly higher in SW patients (54% vs 37%); interestingly, similar frequencies of genotype groups were observed in patient with/without TARTs. Mean glucocorticoid doses did not differ in patients with and without TARTs as well as fludrocortisone doses in SW patients with and without TARTs (p>0.05 for both). Mean 17OHP, D4 and T levels did not differ in both patient groups; mean ACTH levels were 305.3+/-282 vs. 103.2+/-81.9pg/ml in patients with and without TART, respectively (p>0.05). Mean renin levels were significantly higher in patients with TARTs than in those without (152.4+/-116.8 vs. 93.8+/-96.4mIU/ml). Testicular function parameters (mean inhibin B, FSH, LH levels and frequency of abnormal sperm analysis) were worse in the TART group vs without TART (p Conclusion in our series, a high frequency of TARTs was observed, leading to male fertility impairment. An additive renin stimulatory effect, instead of long-term hormonal control or genotype, seemed to be the major role in TARTs development. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Background: Newborn screening for congenital adrenal hyperplasia (CAH-NBS) is not yet a worldwide consensus, in part due to inconclusive evidence regarding cost-effectiveness because the analysis requires an understanding of the short- and long-term costs of care associated with delayed diagnosis.Objective: The present study aimed to conduct a cost-effectiveness analysis (CEA) to compare the costs associated with CAH-NBS and clinical diagnosis.Methods: A decision model comparing the two strategies was tested by sensitivity analysis. The cost analysis perspective was the public health system. Unscreened patients' data were extracted from medical records of Hospital das Clinicas, Saõ Paulo, and screened data were extracted from the NBS Referral Center of São Paulo. The population comprised 195 classical patients with CAH, clinically diagnosed and confirmed by hormonal/CYP21A2 analysis, and 378,790 newborns screened during 2017. Adverse outcomes related to late diagnosis were measured in both cohorts, and the incremental cost-effectiveness ratio (ICER) was calculated. We hypothesized that CAH-NBS would be cost-effective.Results: Twenty-five screened infants were confirmed with CAH (incidence: 1:15,135). The mortality rate was estimated to be 11% in unscreened infants, and no deaths were reported in the screened cohort. Comparing the unscreened and screened cohorts, mean serum sodium levels were 121.2 mEq/L (118.3–124.1) and 131.8 mEq/L (129.3–134.5), mean ages at diagnosis were 38.8 and 17 days, and hospitalization occurred in 76% and 58% of the salt-wasting patients with the in the two cohorts, respectively. The NBS incremental cost was US$ 771,185.82 per death averted, which yielded an ICER of US$ 25,535.95 per discounted life-year saved.Conclusions: CAH-NBS is important in preventing CAH mortality/morbidity, can reduce costs associated with adverse outcomes, and appears cost-effective.

Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up 90% of CAH. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess in both salt-wasting (SW) or simple virilizing (SV) forms. As androgens play a role in the human psychosexual development favoring male psychosexuality, this study was designed to evaluate the impact of androgen exposure on the psychosexuality of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort includes 46,XX individuals (115 female-assigned; 8 male-assigned) with a molecular diagnosis of CAH due to CYP21A2 pathogenic variants in homozygous or compounds heterozygous state. External genitalia virilization was scored using Prader scale. Phenotype, time at diagnosis, sex assignment, and gender change were assessed. The gender role at childhood was assessed through the playmates and toys profile at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report sexual identity. Compliance of glucocorticoid replacement was assessed by adequate testosterone and androstenedione serum levels for age. Results: CAH was diagnosed at the neonatal time in 73% (n=78). Fifth-nine (51%) had the SW form and 49% (n=56) had the SV form. While all cases of SW were diagnosed at the neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (p=

Introduction: Silent corticothop adenomas (SCAs) account for 9 to 19% of nonfunctioning pituitary adenomas and behave as the most agressive pituitary tumors with more invasiveness and high recurrence rate. The identification of these patients during the preoperative stage could predict better surgery results. Some authors refer to high basal ACTH level in the preoperative evaluation as the only marker but until this date, there are no clinical and hormonal markers that could predict its occurrence. The aim of this study is to evaluate the response to desmopressin test and the presence of silent corticothoph tumors. Patients and methods: Among 475 patients with pituitary lesion, which underwent surgery, 332 were pituitary adenomas, (82 were acromegaly, 40 Cushing disease, 178 nonfunctioning adenomas). Twenty-three patients, 17 with Cushing disease, (CD), mean age: 31 y, 13 female and 4 male) and 6 patients with SCA (mean age: 47 y, 5 female and 1 male) had positive ACTH confirmed by immunohistochemical analysis. Clinical characteristics: in the CD group, 53% had hypertension (9/17), 42% diabetes (7/17), 100% dyslipidemia, BMI was 30.7 kg/m2. Among SCA group, 67% hypertension, 50% diabetes, 50% dyslipidemia, BMI was 28 kg/m2. All patients were evaluated with basal ACTH and DHEAS before surgery. Patients with SCA underwent desmopressin test and were compared to CD. Dexamethasone suppression test (DST 1 mg) and 24-hour free urinary test was performed in patients with CD and in two patients with SCA. Response to desmopressin test was considered positive when increase in cortisol was above 20% and in ACTH of 35% using chemiluminescence assay (Immulite 2000). Results: Among CD group, the median (med) basal ACTH was 75.9 pg/mL (30.9 to 211), the med basal cortisol was 22.5 µg/dL (14.5 to 43.5), the med DHEAS was 170 µg/dL (33 to 465), the med 24h urinary free cortisol of 454.5 µg/24 h (149 to 1673) and med basal cortisol after DST 1mg of 15.4 µg/dL (4.7 to 31.5). Among SCA, med basal ACTH was 19.4 pg/mL (9.5 to 65.5), the med basal cortisol was 9.5 µg/dL (7.8 to 16.4) and the med DHEAS was 104.5 µg/dL (82 to 127). Only 4 patients with CD had macroadenomas. All of them responded with ACTH increase (med increase of 98%, 31.6 to 377%), and only 4 did not respond to cortisol increase (med increase of 54.4%, 0 to 167%). All patients with SCA had macroadenomas. Only one patient did not respond to ACTH increase (med increase of 123.5%, 9.5 to 1522%, 9.5 to 1522%), and 3 patients did not respond to cortisol increase (med increase of 17.9%, 0 to 234%). Discussion: SCA are invasive tumors, with high recurrence and tests predicting their occurrence are missing. We hypothesized that as ACTH is present in the adenoma a response to desmopressin test could exist (like CRH). Conclusion: The desmopressin test can be a useful tool in the evaluation of SCA and can predict pathological phenotype in preoperative tumors.

Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up of 90% of CAH. It is caused by several mutations in the CYP21A2 gene. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess, either with salt-wasting or simple virilizing forms. Androgens play a crucial role in the human psychosexual development favoring male psychosexuality. This study was designed to evaluate the impact of androgens on psychosexuality of a cohort of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort is made up of 94 four individuals with proved molecular defect of the CYP21A2 gene. External genitalia virilization was scored using Prader scale. Clinical phenotype, age at diagnosis, sex assignment, gender reassignment and gender change were all assessed. The gender role at childhood was assessed through the playmates and favorite toys at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report and sexual attractiveness. Compliance of glucocorticoid replacement was assessed by serum testosterone and 17OHP levels. Results: CAH was diagnosed at neonatal time in 67% (61 out 94). 51% (n=48) had the salt-wasting form (SW) and 49% (n=46) had the simple virilizing form (SV). While all cases of SW were diagnosed at neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (F 38.9; p=

Context No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency. Objective To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency. Design Observational, retrospective, longitudinal analysis. Patients A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison disease (AD) were analysed. Main outcome measures PRC, electrolytes, blood pressure (BP), and anthropometric parameters were used to predict their utility in optimizing MC replacement dose. Results PRC was low, normal, or high in 19%, 36%, and 44% of patients, respectively, with wide variability in MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC. Conclusions The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration.

Objective To establish short- and long-term adverse outcome frequencies related to a late diagnosis of congenital adrenal hyperplasia (CAH) in the absence of newborn screening (NBS) and to determine respective treatment costs, which have never been reported. Design A retrospective analysis of a CAH cohort diagnosed without NBS. Methods We evaluated medical record data concerning 195 patients (141 females) diagnosed with CAH through clinical suspicion and confirmed using hormonal and CYP21A2 analysis, who were followed from 1980 to 2016 at Sao Paulo University. We measured mortality, dehydration, mental impairment frequencies, and hospitalization length outcomes in the salt-wasting form; the frequency of genetic females raised as males in both forms, frequency of depot GnRh analog (GnRha) and GH therapies in the simple virilizing form, and related outcome costs were calculated. Results Mortality rates and associated costs, varying from 10% to 26% and from $2,239,744.76 to $10,271,591.25, respectively, were calculated using the Brazilian yearly live-births rate, estimated productive life years, and gross domestic product. In the salt-wasting form, 76% of patients were hospitalized, 8.6% were mentally impaired, and 3% of females were raised as males (total cost, $86,230/salt-wasting patient). GnRha and growth hormone were used for 28% and 14% of simple virilizing patients, respectively, and 18% of females were raised as males (preventable cost, $4232.74/simple virilizing patient). Conclusions A late CAH diagnosis leads to high mortality and morbidity rates, notably increasing public health costs, and may result in physical and psychological damage that is not easily measurable.

SummaryIntroduction The primary concern related to congenital adrenal hyperplasia (CAH) newborn screening (NBS) is the high rate of false-positive results (FPR) associated with prematurity; false-negative results (FNR) can also occur due to precocious sample collection. Objective To determine the neonatal 17-hydroxyprogesterone (N17OHP) normal range in newborns in Sao Paulo using different references according to age and birthweight (BW) and to establish the optimal NBS cut-off levels. Methods Neonatal 17-hydroxyprogesterone levels from 271 810 newborns (NBs) according to sample collection time (G1: 48– 2500 g) were evaluated. N17OHP was measured by an fluoroimmunoassay, and serum 17OHP was measured by liquid chromatography-mass spectrometry. Affected and asymptomatic NBs with persistently increased 17OHP levels were submitted to CYP21A2-sequencing. Results Neonatal 17-hydroxyprogesterone levels in G1 were lower than G2 in all BW groups (P < 0·001). The FPR rate in G1/G2 was 0·2% using the 99·8th and 0·5% using the 99·5th percentile. The 99·8th percentile N17OHP value was the best cut-off for distinguishing between unaffected and affected NBs. Forty-four salt wasters, and five simple virilisers were diagnosed; N17OHP levels ranged from 93·3 to 2209·8 nmol/l, and no affected neonates with FNR were identified. The positive predictive value in G1 and G2 using the 99·8th percentile was 5·6% and 14·1%, respectively, and 2·3% and 7%, respectively, using the 99·5th percentile. Molecular tests identified two NBs with the nonclassical form among the 29 FPR. Conclusion Neonatal 17-hydroxyprogesterone levels adjusted to sample collection age and birthweight reduced the FPR, and the use of N17OHP values based upon the 99·8th percentile improved the NBS efficacy.

The congenital adrenal hyperplasia population seems to have an intrinsic tendency to a high frequency of low bone mass. However in this single-center and long-term evaluated cohort, the simplified corticoid regimen, with exclusive dexamethasone single dose reposition during adulthood, did not represent a risk factor for decrease in bone health. The impact of long-term and supposedly physiological doses of gluco and mineralocorticoid (GC/MC) on bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) remains discordant among studies, which contain different clinical forms and corticoid regimens. Our aim was to evaluate the BMD in CAH adults receiving similar GC regimen since childhood and to correlate it with GC/MC cumulative doses. Only patients with good compliance, who used cortisone acetate (CA) during childhood and dexamethasone after the final height achievement. Cumulative GC/MC doses were calculated from diagnosis until last evaluation. BMD was analyzed by the first and last energy X-ray absorptiometry (DXA) scans performed. Twenty simple virilizing (SV) and 14 salt wasting (WS) whose mean age was 26 ± 6 years, mean CA, dexamethasone, and fludrocortisone cumulative doses were 63,813 ± 32,767, 812 ± 558, and 319 ± 325 mg/m2, respectively. Based on the last DXA, low BMD was observed in 11% of patients, total hip Z-score was lower in the SW than SV form (p = 0.04). Cumulative CA dose had an inverse correlation with femoral neck Z-score (p

Context No consensus has been reached regarding the glucocorticoid (GC) to use for congenital adrenal hyperplasia (CAH) during adulthood. Dexamethasone (DEX), because of its longer half-life, could improve compliance; however, no data are available regarding the long-term effects of DEX therapy. Objective To analyze the metabolic effect of DEX therapy for adults with CAH. Design Retrospective analysis of a CAH cohort receiving DEX therapy. Setting Medical School Hospital, São Paulo University, Brazil. Participants Sixty patients with well-controlled classic CAH (41 women; 30 with salt-wasting) receiving DEX after achievement of final height. Interventions None. Main Outcome Measures Clinical, laboratory, and metabolic data were compared immediately before DEX and at the last evaluation. Results The mean age at the last evaluation was 31.9 ± 9.6 years, and the duration of DEX therapy was 11.5 ± 4.9 years. The mean DEX dose was 0.18 ± 0.07 mg/m2/d. The body mass index SD score (1.6 ± 1.6 vs 1.5 ± 1.5 mg/m2; P = 0.65) and obesity prevalence (27% vs 27%) did not differ between evaluations. However, the waist/height ratio (WtHR) had increased from 0.54 ± 0.08 to 0.56 ± 0.1 (P = 0.001). An increase in the homeostatic model assessment for insulin resistance index (2.5 ± 1.3 vs 2.8 ± 1.7; P = 0.03) was observed and positively correlated with the WtHR (r = 0.54). The prevalence of metabolic syndrome (7% vs 10%; P = 0.7) and hypertension (15% vs 13.3%; P = 0.8) did not differ significantly between the two evaluations. Conclusions Long-term and low-dose DEX therapy did not lead to increases in obesity or metabolic syndrome, although it was associated with an increased WtHR and greater homeostatic model assessment for insulin resistance observed with chronic use of GCs. DEX appears to be an acceptable option to treat adult CAH.

Subfertility rate has been observed in women with classical CAH, being inversely correlated with the severity of enzymatic defect. Psychosexual behaviors, genital abnormalities, chronic anovulation and/or excessive androgen exposure could corroborate for this finding. However, there are scarce data in the literature evaluating reproductive outcomes in CAH women. Objective: To evaluate the reproductive outcomes in women with classical CAH. Patients: 84 females with 33±11yrs old: 80 with 21-hydroxylase deficiency and 4 with 11β-hydroxylase deficiency (11OHD), were selected. Methods: Data of Prader score, age at first genitoplasty, sexual activity, sexual orientation, desire to conceive, fecundity rate and pregnancy outcomes were analyzed. Chi-square and T tests were used. Results: Prader score and age at feminizing genitoplasty (3.4±3yrs) did not differ between patients with and without desire to conceive. Among the 84 patients, 27% have never tried sexual activity, due to shame of their genitalia. Homosexual and bisexual orientations were identified in 15% and 1.2% of patients, respectively; 38% of all patients were engaged in stable relationships. Desire to conceive was expressed by 26/84 of patients, being lower in salt wasters-SW (28%) than simple virilizers (67%), and the reference population (76%, p

Background Most congenital adrenal hyperplasia (CAH) patients carry CYP21A2 mutations derived from conversion events involving the pseudogene, and the remaining carry new mutations. Objective To review causal mutations and genotype–phenotype correlation in 480 Brazilian patients. Methods DNA was extracted from 158 salt-wasters (SWs), 116 simple virilizing (SV), and 206 nonclassical (NC) patients. Fourteen point mutations were screened by allele-specific PCR, large rearrangements by Southern blotting/MLPA, and sequencing was performed in those with incomplete genotype. The gene founder effect was analyzed by microsatellite studies. Patients were divided into six genotypes (Null; A: 20% of residual enzymatic activity (EA); D: unknown EA; E: incomplete genotype). Results Targeted methodologies defined genotype in 87.6% of classical and in 80% of NC patients and the addition of sequencing in 100 and 83.5%, respectively. The most frequent mutations were p.V281L (26.6% of alleles), IVS2-13A/C>G (21.1%), and p.I172N (7.5%); seven rare mutations and one novel mutation (p.E351V) were identified. Gene founder effect was observed in all but one (p.W19X) mutation. Null, A, B, and C genotypes correlated with SW (88%), SW (70%), SV (98%), and NC forms (100%), respectively. In group D, the p.E351V mutation correlated with classical form and group E comprised exclusively NC-patients. ACTH-stimulated 17OHP level of 44.3ng/mL was the best cutoff to identify NC-patients carrying severe mutations. Conclusions We identified a good genotype–phenotype correlation in CAH, providing useful data regarding prediction of disease’s severity; moreover, we suggest that ACTH-stimulated 17OHP levels could predict carrier status for severe mutations. Sequencing is essential to optimize molecular diagnosis in Brazilian CAH patients.