Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

Genotype-Specific Cortisol Reserve in a Cohort of Subjects With Nonclassic Congenital Adrenal Hyperplasia (NCCAH).

CONTEXT: Recent guidelines suggest that patients with nonclassic congenital adrenal hyperplasia (NCCAH) stop glucocorticoid therapy after achieving adult height. However, these guidelines do not differentiate between NCCAH genotype groups. OBJECTIVE: Compare ACTH-stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the rate of partial cortisol insufficiency in subjects with NCCAH carrying one mild and one severe (mild/severe) mutation vs subjects with biallelic mild (mild/mild) mutations. METHODS: Retrospective evaluation of the medical records of 122 patients who presented with postnatal virilization and were diagnosed with NCCAH. Patients underwent standard intravenous 0.25 mg/m2 ACTH stimulation testing. Those with stimulated 17OHP level ≥40 nmol/L were screened for the 9 most frequent CYP21A2 gene mutations followed by multiplex ligation-dependent probe amplification. A stimulated cortisol level below 500 nmol/L was defined as partial cortisol deficiency. RESULTS: Patients were subdivided into 3 genotype groups: 77 carried the mild/mild genotype, mainly homozygous for p.V281L mutation; 29 were compound heterozygous for mild/severe mutation, mainly p.V281L/p.I2Splice, and 16 were heterozygous for p.V281L, and were excluded from statistical evaluation. Stimulated cortisol levels were significantly lower in the mild/severe than in the mild/mild group (mean ± SD, 480 ± 90 vs 570 ± 125 nmol/L, P < .001). The mild/severe group exhibited a significantly higher rate of partial cortisol insufficiency (21/28, 75% vs 28/71, 39%, P = .004). Peak 17OHP was significantly higher in the mild/severe group (198 ± 92 vs 118 ± 50 nmol/L, P < .001). CONCLUSION: The high rate of partial adrenal insufficiency in the mild/severe group underscores the need to carefully consider the value of glucocorticoid therapy cessation and the importance of stress coverage in this group.

Polyethylene glycol thyroid-stimulating hormone (PEG-TSH) testing in the management of pediatric thyroid dysfunction.

PURPOSE: The polyethylene glycol (PEG) methodology is used for investigating incongruities in laboratory assays, such as thyroid-stimulating hormone (TSH) measurements. The aim of the study is to investigate the practical application of PEG-TSH testing in cases of discrepancies between elevated TSH and normal free thyroxine (FT4) levels. METHODS: A real-life observational study conducted in a tertiary medical center. The hospital's electronic database was queried for TSH tests performed in pediatric patients between 2015 and 2023. Of those, PEG-TSH were identified. Patients' clinical and biochemical characteristics and PEG-TSH-guided management were assessed. RESULTS: In total, 2949 TSH tests were performed in 891 children and adolescents for various indications. Among them were 61 (2.1%) PEG-TSH results, mean age 7.1 ± 5.3 years, of 38 patients (4.3%), comprised of 16 with congenital hypothyroidism, 16 with subclinical hypothyroidism, and 6 with Hashimoto thyroiditis. Both the TSH and the PEG-TSH levels of patients with congenital hypothyroidism were higher than those of the other two groups (P = 0.021 and P = 0.009, respectively), with no group differences in FT4 levels. Spearman's correlation analysis revealed a strong association between TSH and PEG-TSH levels: r = 0.871, P < 0.001. In nearly one-half of the cases, clinical decisions made by clinicians (decreasing the dose or not initiating L-thyroxine treatment) were affected by the PEG-TSH results. CONCLUSION: Our findings support PEG-TSH testing for determining appropriate TSH levels and avoid unnecessary thyroid hormone treatment among children and adolescents. We propose the suitability of managing their clinical condition based upon age-appropriate clinical parameters and FT4 levels when their PEG-TSH levels are within the normal range.

Body composition in children and adolescents with non-classic congenital adrenal hyperplasia and the risk for components of metabolic syndrome: An observational study.

Background: Treated or untreated non-classic congenital adrenal hyperplasia (NCCAH) diagnosed in childhood could pose an increased risk of obesity and metabolic derangements in adolescence and early adulthood. We aimed to explore the interaction between muscle-to-fat ratio (MFR) and components of metabolic syndrome in pediatric subjects with NCCAH. Methods: This retrospective observational study was conducted in the Tel Aviv Medical Center from January 2018 to January 2022. The study group comprised 75 subjects (26 males) with NCCAH (61 hydrocortisone-treated [21 males] and 14 untreated [5 males]) and 134 healthy sex- and age-matched subjects (41 males) with normal puberty served as controls. Body composition was measured by bioelectrical impedance analysis (BIA) and muscle-to-fat ratio (MFR) z-scores were calculated. Stepwise linear regression models were applied to evaluate explanatory variables for MFR z-scores, blood pressure percentiles, lipid profiles, and glucose metabolism. Results: The median age [interquartile range] was 7.5 years [5.3, 8.8] at NCCAH diagnosis and 12.3 years [8.9, 15.4] at BIA. The median cumulative hydrocortisone dose was 7620 mg/m2 [2547, 12903]. Subjects with NCCAH had higher mean BMI z-scores and lower median MFR z-scores compared to controls [(0.47 ± 0.97 vs. -0.19 ± 1.04, p<0.001) and (-0.74 [-1.06, -0.14] vs.-0.37 [-0.99, 0.15], p=0.045), respectively]. The linear regression models dependent variables and their explanatory variables were: MFR z-score (R2= 0.253, p<0.001) - socioeconomic position index (ß=0.348, p=0.003), birthweight z-score (ß=-0.258, p=0.013), and duration of hydrocortisone treatment in years (ß=0.048, p=0.023); systolic blood pressure percentile (R2 = 0.166, p<0.001) - MFR z-score (ß=-9.75, p<0.001); TG/HDL ratio (R2 = 0.116, p=0.024) - MFR z-score (ß=-0.300, p=0.024). No significant variables were found for glucose. Conclusions: Children and adolescents with NCCAH have a body composition characterized by an imbalance between muscle and fat tissues, which may place them at increased risk for early-onset cardiometabolic derangements. It is reassuring that glucocorticoid therapy aimed to alleviate androgen overproduction does not appear to adversely affect their body composition.

Blood pressure dynamics after pubertal suppression with gonadotropin-releasing hormone analogs followed by estradiol treatment in transgender female adolescents: a pilot study.

OBJECTIVES: The benefits of gonadotropin-releasing hormone analogues (GnRHa) in the treatment of central precocious puberty are well established, and their use is regarded as both safe and effective. Possible adverse effects on blood pressure (BP) and cardiac outcomes, body composition, bone health and brain development, however, continue to be of some concern. The aim of this study was to analyze BP changes in transgender female adolescents before and after receiving GnRHa and after adding estrogen treatment. METHODS: This was a retrospective pilot study. We analyzed systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding estrogen. RESULTS: Nineteen transgender female adolescents received GnRHa and 15 continued to estrogen treatment. Their baseline SBP and DBP percentiles did not change significantly after either GnRHa or the addition of estrogen treatment. CONCLUSIONS: Blood pressure is apparently not affected by GnRHa or GnRHa + estrogen treatment in transgender female adolescents. Further larger studies are indicated to confirm these findings.

Paediatricians' practices and knowledge of corticosteroids: A national survey.

AIM: To explore corticosteroid prescription practices and knowledge among paediatricians. METHODS: The Paediatricians Corticosteroids Survey, a cross-sectional, web-based survey distributed to Israeli paediatricians between February and July 2018. RESULTS: Three hundred and forty-nine paediatricians (105 general paediatricians, 207 subspecialists and 37 paediatric endocrinologists) participated. Two hundred and three (58.2%) had >10 years of paediatric clinical experience and treated >60 patients/wk on average, 175/318 (55%) prescribed corticosteroids to >10% of their patients. On knowledge items, 11/266 (4.1%) responded 'not sure' when tapering of steroids is required, 22/268 (8.2%) to what 'stress dose' meant and 27/268 (10.1%) when a stress dose is required. Multivariate linear analysis showed higher scores were associated with training in paediatric endocrinology (ß = 2.271, P = 0.032); medical practice only in a subspecialty (ß = 1.909, P = 0.041) or in both general paediatrics and a subspecialty (ß = 2.023, P = 0.014), compared to general paediatrics alone and medical studies in Israel (ß = 1.059, P = 0.035). Overall, 96.2% thought continued medical education (CME) sessions would be helpful. CONCLUSION: Our findings suggest that despite clinical experience with corticosteroid usage, respondents demonstrated gaps in knowledge for potentially life-threatening situations. Corticosteroid-based CME programs are warranted to improve paediatricians' knowledge and patient management.

Blood Pressure Dynamics After Pubertal Suppression with Gonadotropin-Releasing Hormone Analogs Followed by Testosterone Treatment in Transgender Male Adolescents: A Pilot Study.

Purpose: We analyzed blood pressure (BP) changes in transgender male adolescents treated with gonadotropin-releasing hormone analogs (GnRHa) and after adding testosterone treatment. Methods: This was a retrospective pilot study. Outcome measures included systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding testosterone. Results: Fifteen transgender male adolescents received GnRHa. DBP percentiles increased significantly after GnRHa treatment (from 55.9% ± 26.4 to 73.6% ± 9.4, p = 0.019). BP levels did not meet criteria for hypertension. DBP percentiles were restored after adding testosterone. Conclusion: GnRHa may increase DBP in transgender male adolescents, and testosterone treatment may restore it. Further larger studies are indicated.

Oocyte retrieval outcomes among adolescent transgender males.

PURPOSE: To compare fertility preservation (FP) outcomes among adolescent transgender males with those of cisgender females. METHODS: This retrospective cohort study included nine adolescent transgender males and 39 adolescent cisgender females who underwent FP between January 2017-April 2019 and September 2013-April 2019, respectively. The transgender males were referred before initiating testosterone, and the cisgender females were referred due to cancer diagnosis before starting anticancer treatment. Statistical analyses compared assisted reproductive technology (ART) data and FP outcomes between two groups. RESULTS: Basal FSH levels (5.4 ± 1.7 mIU/mL) and AFC (19.8 ± 5.6) of all transgender males were normal compared with standard references. The mean age of transgender males and cisgender females was similar (16.4 ± 1.1 vs 15.5 ± 1.3 years, respectively, P = 0.064). The amount of FSH used for stimulation was significantly lower among the former compared with the latter (2416 ± 1041 IU vs 4372 ± 1877 IU, P < 0.001), but the duration of stimulation was similar (12.6 ± 4.0 and 10.1 ± 2.8 days, P = 0.086). Peak estradiol level was significantly higher among transgender males compared with cisgender females (3073 ± 2637 pg/mL vs 1269 ± 975 pg/mL, respectively, P = 0.018), but there were no significant differences in number of retrieved oocytes between the two groups (30.6 ± 12.8 vs 22 ± 13.2, P = 0.091), number of MII oocytes (25.6 ± 12.9 vs 18.8 ± 11.2, P = 0.134), or maturity rates (81.5 ± 10.0% vs 85.4 ± 14.6%, P = 0.261). CONCLUSIONS: Adolescent transgender males have an excellent response to ovulation stimulation before initiating testosterone treatment. Oocyte cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

CHILDREN AND ADOLESCENTS WITH GENDER DYSPHORIA IN ISRAEL: INCREASING REFERRAL AND FERTILITY PRESERVATION RATES.

Objective: To describe patient characteristics at presentation, management, and fertility preservation rates among a cohort of Israeli children and adolescents with gender dysphoria (GD). Methods: We performed a retrospective chart review of 106 consecutive children and adolescents with GD (<18 years) referred to and followed at the multidisciplinary Israeli Pediatric Gender Dysphoria Clinic from March 2013 through December 2018. Results: Of the 106 patients, 10 were prepubertal (9 prepubertal transgender females), and 96 were pubertal (38 pubertal transgender females). The GD population increased 11-fold since the establishment of our clinic in 2013. The subject's median age at referral was 15.5 years (range, 4.6 to 18 years). At the time of referral, 91 (95%) of the pubertal group had completed sexual maturation in their assigned gender at birth. Thirteen (13.5%) patients had attempted suicide, and 11 (11.5%) reported having had suicidal thoughts. Fourteen (45%) pubertal transgender females and 3 (6.5%) pubertal transgender males completed fertility preservation. Gonadotropin-releasing hormone analog treatment was prescribed in 77 (80%) patients at a mean age of 15.9 ± 1.6 years. Gender-affirming hormones were prescribed in 61 (64%) patients at a mean age of 16.5 ± 1.3 years. No severe side effects were recorded. Two (2%) of the pubertal group expressed regret about medical treatment. Conclusion: Children and adolescents with GD are presenting for medical attention at increasing rates. Israeli adolescents with GD have high fertility preservation rates, perhaps attributable to cultural perspectives. Taking advantage of the option to preserve fertility can be achieved when proper counseling is both available and promoted by medical personnel. Abbreviations: GAH = gender-affirming hormone; GD = gender dysphoria; GnRHa = gonadotropin-releasing hormone analog; MHP = mental health professional.

WOMEN WITH NONCLASSIC CONGENITAL ADRENAL HYPERPLASIA HAVE GENDER, SEXUALITY, AND QUALITY-OF-LIFE FEATURES SIMILAR TO THOSE OF NONAFFECTED WOMEN.

Objective: Females with the severe classic forms of congenital adrenal hyperplasia reportedly have a higher frequency of atypical gender identity, nonheterosexual sexual relationships, and cross-gender role behavior. Comparable data and quality-of-life measures among those with the milder, more prevalent form, nonclassic congenital adrenal hyperplasia, are scarce. We aimed to assess health-related quality of life, gender identity, role, and sexual orientation in women with nonclassic congenital adrenal hyperplasia via a prospective, questionnaire-based, case-control study. Methods: Thirty-eight women with nonclassic congenital adrenal hyperplasia (median age 34 years; range, 18 to 44 years) and 62 age-matched female controls were recruited. Outcome measures included the Multi-Gender Identity, Sexuality, and World Health Organization (WHO) quality-of-life questionnaires. Results: Sociodemographic parameters (marital status, number of children, and educational level) were similar for both groups, as were most measures of the Multi-Gender Identity, Sexuality, and WHO quality-of-life questionnaires. However, "sometimes-feeling-as-a-man and sometimes-feeling-as-a-woman" were more frequently reported in the study group compared to the controls (7/38 [18.4%] vs. 3/62 [4.8%], respectively; P = .02). Furthermore, more nonclassic congenital adrenal hyperplasia women reported first falling in love with a woman (4/37 [10.8%] vs. 0/58 [0%]; P = .02). Conclusion: Our findings suggest possible subtle differences in gender identity and sexual orientation between adult nonclassic congenital adrenal hyperplasia females and controls. Quality of life was not impaired in individuals within the study group. The impact of exposure to mildly elevated androgen levels during childhood and adolescence on the female brain warrants more in-depth assessment in further studies. Abbreviations: CAH = congenital adrenal hyperplasia; Multi-GIQ = Multi-Gender Identity Questionnaire; NCCAH = nonclassic congenital adrenal hyperplasia; QoL = quality of life.

Primary Ovarian Insufficiency Nationwide Incidence Rate and Etiology Among Israeli Adolescents.

PURPOSE: The aim of the study was to estimate the current incidence and the distribution of etiologies of primary ovarian insufficiency (POI) in a nationwide study. The prevalence of POI in young adult women has recently increased, but the data cited for adolescents are more than three decades old. METHODS: Data regarding females aged <21 years diagnosed with POI during the years 2000-2016 were collected from all the pediatric endocrinology units in Israel. POI was defined by at least 4 months of amenorrhea in association with menopausal levels of follicle-stimulating hormone. Iatrogenic cases were excluded. RESULTS: For the 130 females aged <21 years included in the study, the distribution of POI etiologies was Turner syndrome/mosaicism in 56 (43%), idiopathic in 35 (27%), and other (developmental, genetic, metabolic, adrenal, and autoimmune) in 39 (30%) females. During the years 2009-2016, compared with 2000-2008, the incidence rate of new POI diagnoses per 100,000 person-years doubled (4.5 vs. 2.0; p value <.0001), and incidence rates of idiopathic and other etiologies increased by 2.6 (p value = .008) and 3.0 (p value = .002), respectively. In contrast, the incidence of Turner syndrome was constant (p value = .2). In the age group of 15-21 years, the current incidence of non-Turner POI in adolescents is one per 100,000 person-years. CONCLUSIONS: In this nationwide study, the incidence rate of POI in youth aged <21 years was one tenth of the rate that is commonly cited. A significant increase in the rate of POI in non-Turner females was observed over the last decade. Contributions of environmental and epigenetic factors should be studied.

HEALTH-RELATED QUALITY OF LIFE IN CHILDREN AND ADOLESCENTS WITH NONCLASSIC CONGENITAL ADRENAL HYPERPLASIA.

Objective: Nonclassic congenital adrenal hyperplasia (NCCAH) is a late-onset milder form of congenital adrenal hyperplasia that differs dramatically from the classic form. Health-related quality of life (HRQOL) in pediatric patients with the sole diagnosis of NCCAH has not been determined; therefore, in this study, we aimed to determine whether HRQOL is compromised in comparison to the general population. Methods: Single-center, cross-sectional, case-control study. Twenty-three hydrocortisone-treated children and adolescents (7 males) diagnosed with NCCAH by cosyntropin stimulation test and CYP21A2 gene mutation analysis were recruited to this study; 6 healthy siblings were also recruited. HRQOL was assessed by the child and parent-proxy PedsQL Inventory and compared between NCCAH subjects and healthy siblings. HRQOL scores of NCCAH subjects were compared with known standards from the U.S. and Israeli general healthy populations. Anthropometric measurements of children and parents were performed and compared between NCCAH subjects and healthy siblings. Pearson correlation coefficients were calculated. Results: HRQOL scores of the participants and parents did not differ between NCCAH subjects and healthy siblings. The HRQOL emotional domain scores of the NCCAH patients and parent were significantly lower than the healthy U.S. pediatric population (P = .046) but not different from established standards of the healthy Israeli population (P = .583). Anthropometric measurements were within the normal range and did not differ between NCCAH subjects and their siblings. Total, school functioning, and psychosocial HRQOL domain scores were positively correlated with body mass index-standard deviation score in NCCAH subjects. Conclusion: HRQOL was not adversely affected by NCCAH among adequately treated children and adolescents. Abbreviations: BMI = body mass index; CAH = congenital adrenal hyperplasia; HRQOL = health-related quality of life; NCCAH = nonclassic congenital adrenal hyperplasia; PedsQL = Pediatric Quality of Life Inventory; SDS = standard deviation score.

Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors.

The aim of the study was to assess the epidemiology and risk factors of adrenal crises (AC) in children with adrenal insufficiency (AI). Children diagnosed with AI between 1990 and 2017 at four Israeli pediatric endocrinology units were studied. Demographic and clinical data were retrieved retrospectively from their files. The study population consisted of 120 children (73 boys, 47 girls) and comprised 904 patient years. Median age at diagnosis was 0.3 years (0-17.5). Thirty-one AC events in 26 children occurred during the study period, accounting for a frequency of 3.4 crises/100 patient years. Fifty-two percent of AC events occurred at presentation. The significant risk factors for developing AC were the following: younger age at diagnosis (P = 0.003), primary AI vs. secondary AI (P = 0.016), specific diagnosis of autoimmune AI, adrenal hypoplasia congenita and salt wasting congenital adrenal hyperplasia (P < 0.001), mineralocorticoid treatment (P < 0.001), and recurrent hospital admissions (P > 0.001). After applying a stepwise logistic regression model, only the group of diagnoses, including salt wasting CAH, AHC, and Addison's disease, remained significant predictor of AC (OR 17.5, 95% CI 4.7-64.9, P < 0.001). There was no AC-associated mortality during the study period.Conclusions: Since significant percent of AC events occurred at presentation, measures to increase the awareness to signs and symptoms of AI among primary care physicians should be taken. Efforts to prevent AC should be focused on younger patients, especially those with primary AI. What Is Known: • Diagnosis and long-term management of pediatric patients with adrenal insufficiency (AI) remain a challenge. • Adrenal crises (AC) pose life-threatening emergencies in affected youngsters. Studies on the rate and risk factors of AC in children with AI are scarce, and they were done mainly on children with congenital adrenal hyperplasia (CAH). What Is New: • The rate of AC was relatively low and there was no AC-associated mortality during the study period. • Children with primary AI were at higher risk for AC than children with secondary AI. Specifically, children with salt wasting CAH, adrenal hypoplasia congenita, and Addison's disease at the highest risk.

Correction: The effect of CAG repeats length on differences in hirsutism among healthy Israeli women of different ethnicities.

[This corrects the article DOI: 10.1371/journal.pone.0195046.].

The effect of CAG repeats length on differences in hirsutism among healthy Israeli women of different ethnicities.

PURPOSE: Variations in the degree of hirsutism among women of different ethnic backgrounds may stem from multiple etiologies. Shorter length of the polymorphic CAG repeats of the androgen receptor (AR) gene may be associated with increased activity of the receptor leading to hirsutism. We hypothesized that there are ethnic differences in the degree of hirsutism that is unrelated to androgen levels among Israeli women, and that the CAG repeats length may contribute to these differences. Anti-androgenic therapies, such as spironolactone, could be suggested if a shorter CAG repeats length is found to affect the difference in the degree of hirsutism between the ethnic groups. METHODS: Healthy Israeli Jewish women aged 18-45 years of Ashkenazi and non-Ashkenazi origin were invited to participate. Hirsutism was assessed using the simplified Ferriman-Gallwey (sFG) score, and serum total testosterone levels were measured as well. The CAG repeats length was determined by PCR. Methylation-sensitive methods were used to detect the fractional activity of each allele, and the weighted mean was calculated for the CAG repeats length. RESULTS: One-hundred and eight women were recruited (49 Ashkenazi and 59 non-Ashkenazi). The Ashkenazi women had a significantly lower degree of hirsutism (P<0.01), lower mean BMI (P = 0.003), total testosterone levels (P = 0.017), and longer weighted bi-allelic CAG repeats mean (P = 0.015) compared to non-Ashkenazi women. For the group as a whole, there was a significant negative correlation between the number of CAG repeats in the AR gene and the sFG score, while the number of repeats was not related to testosterone levels. Stepwise logistic regression revealed that ethnic origin and the CAG repeats length were the strongest factors affecting hirsutism (P<0.001, P = 0.03, respectively). CONCLUSIONS: There is a significant difference in the degree of hirsutism between Ashkenazi and non-Ashkenazi women in Israel that is partially explained by CAG repeats length.

Pregnancy in women with nonclassic congenital adrenal hyperplasia: Time to conceive and outcome.

OBJECTIVE: Nonclassic congenital adrenal hyperplasia (NCAH) is common among Ashkenazi Jews (1:400). It is associated with various degrees of postnatal virilization, irregular menses and infertility. Therapy of symptomatic subjects consists of physiologic doses of glucocorticoids. The objective of this study was to evaluate the effect of glucocorticoid treatment on fertility and on pregnancy outcome in women with NCAH. DESIGN, SETTING AND PATIENTS: This retrospective study included 75 women diagnosed with NCAH who were followed in our clinic and sought fertility between 2008 and 2015. RESULTS: Seventy-two women succeeded in conceiving (187 pregnancies). Time to conception was 4.0 ± 7 months without and 3.3 ± 3 months with glucocorticoid therapy (P = .43). Seventeen pregnancies were achieved by glucocorticoid therapy after failure to conceive spontaneously. Time to conception before therapy initiation was 10.2 ± 11.4 months compared to 3.3 ± 3.4 months after therapy initiation (P = .02). Of 187 pregnancies, 135 (72%) resulted in live births, 38 (20.3%) ended in spontaneous miscarriages during the first trimester, seven (3.7%) were electively terminated, three (1.6%) were ectopic and four (2.1%) were ongoing during the study with similar rate in glucocorticoid treated and untreated pregnancies. CONCLUSIONS: The 96% pregnancy rate among our cohort of NCAH females was similar to the 95% rate reported for the normal population. Glucocorticoid therapy may shorten the time to conceive in a subgroup of women with NCAH. Glucocorticoid therapy did not affect the rate of first trimester miscarriage. Our 77% live birth rate was similar to the 72% live birth rate in the current healthy US population.

Yield and clinical efficacy of funduscopic examinations performed in the pediatric emergency room.

UNLABELLED: Consultations by ophthalmologists to rule out papilledema are frequently requested by emergency room (ER) physicians. The clinical setting and optimal timing for examination are not well established, and the impact on patient management is unclear. We evaluated the yield of emergency funduscopic examinations, aiming at establishing the optimal timing and efficacy of the consultation. The medical records of all children aged 0-18 years referred for funduscopic examinations from the ER between June 2010 and May 2011 were reviewed. Of 19,772 ER visits, 1,920 (9.7 %) were seen by an ophthalmologist and 479 (2.4 %) to rule out papilledema. Headache (44.5 %) and head trauma (18.4 %) were the most common indications. Sixty percent of the 479 patients had been symptomatic for <24 h, all having normal eye exams. Only 6/479, with diverse etiologies, depicted papilledema. Among these six children, visual complaints associating with headache were statistically significant to suggest the presence of papilledema (p = 0.014). Seventy-one of the 479 children underwent neuroimaging studies despite normal funduscopic examinations. A single tumor case (medulloblastoma), symptomatic for weeks, had normal funduscopy. CONCLUSION: The vast majority of ER consultations to rule out papilledema show normal findings, particularly among children with signs and symptoms lasting for <24 h. The yield of funduscopy may be higher if visual disturbances are reported. If neuroimaging studies are considered, emergency room ophthalmological consultation is probably not warranted, except for young infants with neurological signs and symptoms in whom retinal hemorrhages suggestive of physical abuse must be ruled out.