Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia.

BACKGROUND: Children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency require treatment with glucocorticoids, usually at supraphysiologic doses, to address cortisol insufficiency and reduce excess adrenal androgens. However, such treatment confers a predisposition to glucocorticoid-related complications. In 2-week phase 2 trials, patients with CAH who received crinecerfont, a new oral corticotropin-releasing factor type 1 receptor antagonist, had decreases in androstenedione levels. METHODS: In this phase 3, multinational, randomized trial, we assigned pediatric participants with CAH, in a 2:1 ratio, to receive crinecerfont or placebo for 28 weeks. A stable glucocorticoid dose was maintained for 4 weeks, and the dose was then adjusted to a target of 8.0 to 10.0 mg per square meter of body-surface area per day (hydrocortisone dose equivalents), provided that the androstenedione level was controlled (≤120% of the baseline level or within the reference range). The primary efficacy end point was the change in the androstenedione level from baseline to week 4. A key secondary end point was the percent change in the glucocorticoid dose from baseline to week 28 while androstenedione control was maintained. RESULTS: A total of 103 participants underwent randomization, of whom 69 were assigned to the crinecerfont group and 34 to the placebo group; 100 (97%) remained in the trial at 28 weeks. At baseline, the mean glucocorticoid dose was 16.4 mg per square meter per day, and the mean androstenedione level was 431 ng per deciliter (15.0 nmol per liter). At week 4, the androstenedione level was substantially reduced in the crinecerfont group (-197 ng per deciliter [-6.9 nmol per liter]) but increased in the placebo group (71 ng per deciliter [2.5 nmol per liter]) (least-squares mean difference, -268 ng per deciliter [-9.3 nmol per liter]; P<0.001); the observed mean androstenedione value, obtained before the morning glucocorticoid dose, was 208 ng per deciliter (7.3 nmol per liter) in the crinecerfont group, as compared with 545 ng per deciliter (19.0 nmol per liter) in the placebo group. At week 28, the mean glucocorticoid dose had decreased (while androstenedione control was maintained) by 18.0% with crinecerfont but increased by 5.6% with placebo (least-squares mean difference, -23.5 percentage points; P<0.001). Headache, pyrexia, and vomiting were the most common adverse events. CONCLUSIONS: In this phase 3 trial, crinecerfont was superior to placebo in reducing elevated androstenedione levels in pediatric participants with CAH and was also associated with a decrease in the glucocorticoid dose from supraphysiologic to physiologic levels while androstenedione control was maintained. (Funded by Neurocrine Biosciences; CAHtalyst Pediatric ClinicalTrials.gov number, NCT04806451.).

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

Development and validation of a computable phenotype for Turner syndrome utilizing electronic health records from a national pediatric network.

Turner syndrome (TS) is a genetic condition occurring in ~1 in 2000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing electronic health record (EHR) have the potential to address these limitations; however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding an average sensitivity of 0.97, specificity of 0.88, and C-statistic of 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS.

Sex Differences in Athletic Performance: Perspectives on Transgender Athletes.

Sex hormone concentrations, particularly testosterone, are primary determinants of sex-based differences in athletic and sports performance, and this relationship may inform fair competition and participation for athletes. This article describes the sex-based dichotomy in testosterone and the implications for sex-based differences in individual sports performance, including factors that relate to athletic performance for transgender individuals, and areas of future investigation.

Behavioral Health Diagnoses in Youth with Gender Dysphoria Compared with Controls: A PEDSnet Study.

OBJECTIVE: To assess the odds of a psychiatric or neurodevelopmental diagnosis among youth with a diagnosis of gender dysphoria compared with matched controls in a large electronic health record dataset from 6 pediatric health systems, PEDSnet. We hypothesized that youth with gender dysphoria would have higher odds of having psychiatric and neurodevelopmental diagnoses than controls. STUDY DESIGN: All youth with a diagnosis of gender dysphoria (n = 4173 age at last visit 16.2 ± 3.4) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables to controls without gender dysphoria (n = 16 648, age at last visit 16.2 ± 4.8) using multivariable logistic regression. The odds of having psychiatric and neurodevelopmental diagnoses were examined using generalized estimating equations. RESULTS: Youth with gender dysphoria had higher odds of psychiatric (OR 4.0 [95% CI 3.8, 4.3] P < .0001) and neurodevelopmental diagnoses (1.9 [1.7, 2.0], P < .0001). Youth with gender dysphoria were more likely to have a diagnosis across all psychiatric disorder subcategories, with particularly high odds of mood disorder (7.3 [6.8, 7.9], P < .0001) and anxiety (5.5 [5.1, 5.9], P < .0001). Youth with gender dysphoria had a greater odds of autism spectrum disorder (2.6, [2.2, 3.0], P < .0001). CONCLUSIONS: Youth with gender dysphoria at large pediatric health systems have greater odds of psychiatric and several neurodevelopmental diagnoses compared with youth without gender dysphoria. Further studies are needed to evaluate changes in mental health over time with access to gender affirming care.

Hepatic abnormalities in youth with Turner syndrome.

BACKGROUND & AIMS: Liver disease in children with Turner Syndrome (TS) is poorly understood relative to associated growth, cardiac and reproductive complications. This study sought to better characterize hepatic abnormalities in a large national cohort of youth with TS. METHODS: Using electronic health record data from PEDSnet institutions, 2145 females with TS were matched to 8580 females without TS on eight demographic variables. Outcomes included liver enzymes (AST and ALT) stratified as normal, 1-2 times above the upper limit of normal (ULN), 2-3 times ULN and >3 times ULN, as well as specific liver disease diagnoses. RESULTS: Fifty-eight percent of youth with TS had elevated liver enzymes. Patients with TS had higher odds of enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), 2-3 times ULN (OR: 2.7, 95% CI: 1.7-3.3) and >3 times ULN (OR: 1.7, 95% CI: 1.3-2.2). They also had higher odds of any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0) and liver tumour/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In a multinomial model, age, BMI and presence of cardiovascular disease or diabetes significantly increased the odds of elevated liver enzymes in girls with TS. CONCLUSIONS: Youth with TS have higher odds for elevated liver enzymes and clinically significant liver disease compared with matched controls. These results emphasize the need for clinical screening and additional research into the aetiology and treatment of liver disease in TS. LAY SUMMARY: Turner Syndrome, a chromosomal condition in which females are missing the second sex chromosome, is often associated with short stature, infertility and cardiac complications. Liver abnormalities are less well described in the literature. In this study, nearly 60% of youth with TS have elevated liver enzymes. Furthermore, patients with TS had a diagnosis of liver disease more often than patients without TS. Our results support the importance of early and consistent liver function screening and of additional research to define mechanisms that disrupt liver function in paediatric TS females.

Kidney hemodynamic function in men and postmenopausal women with type 2 diabetes and preserved kidney function.

The progression of kidney disease may differ between sexes in type 2 diabetes (T2D), with previous studies reporting a slower decline in women. Glomerular hyperfiltration is a key factor driving the kidney function decline. The current study aimed to investigate the differences in kidney hemodynamic function between men and women with T2D. A cross-sectional analysis of pooled data from three studies compared kidney hemodynamic function between men and postmenopausal women with T2D without overt nephropathy. The outcome measures were glomerular filtration rate (GFR; inulin clearance), effective renal plasma flow (ERPF; p-aminohippurate clearance), filtration fraction (GFR/ERPF), and renal vascular resistance (RVR; mean arterial pressure/renal blood flow). Glomerular hydraulic pressure (PGLO) as well as afferent and efferent vascular resistance were estimated by Gomez formulae. Sex differences were assessed with linear regression models adjusted for systolic blood pressure, glucose, use of renin-angiotensin system blockers, and body mass index. In total, 101 men [age: 63 (58-68) yr, body mass index: 31.5 ± 3.9 kg/m2, GFR: 111 ± 18 mL/min, HbA1c: 7.4 ± 0.7%] and 27 women [age: 66 (62-69) yr, body mass index: 30.9 ± 4.5 kg/m2, GFR: 97 ± 11 mL/min, HbA1c: 7.1 ± 0.5%] were included. GFR was higher in men versus women [11.0 mL/min (95% confidence interval: 3.6, 18.4)]. Although statistically nonsignificant, PGLO trended higher in men [1.9 mmHg (95% confidence interval: -0.1, 4.0)], whereas RVR [-0.012 mmHg/L/min (95% confidence interval: -0.022, -0.002)] and afferent vascular resistance were lower [-361 dyn/s/cm5 (95% confidence interval: -801, 78)]. In conclusion, in adults without overt nephropathy, GFR was higher in men compared with women. PGLO also trended to be higher in men. Both findings are possibly related to afferent vasodilation and suggest greater prevalence of hyperfiltration. This could contribute to accelerated GFR loss over time in men with T2D.NEW & NOTEWORTHY In adults with type 2 diabetes, men had higher markers of hyperfiltration, which could potentially explain the accelerated progression of diabetic kidney disease in men compared with women.

Behavioral Health Diagnoses in Youth with Differences of Sex Development or Congenital Adrenal Hyperplasia Compared with Controls: A PEDSnet Study.

OBJECTIVE: To evaluate the odds of a behavioral health diagnosis among youth with differences of sex development (DSD) or congenital adrenal hyperplasia (CAH) compared with matched controls in the PEDSnet database. STUDY DESIGN: All youth with a diagnosis of DSD (n = 1216) or CAH (n = 1647) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables (1:4) with controls (n = 4864 and 6588, respectively) using multivariable logistic regression. The likelihood of having behavioral health diagnoses was examined using generalized estimating equations. RESULTS: Youth with DSD had higher odds of a behavioral health diagnosis (OR, 1.7; 95% CI, 1.4-2.1; P < .0001) and neurodevelopmental diagnosis (OR, 1.7; 95% CI, 1.4, 2.0; P < .0001) compared with matched controls. Youth with CAH did not have an increased odds of a behavioral health diagnosis (OR, 1.0; 95% CI, 0.9, 1.1; P = .9) compared with matched controls but did have higher odds of developmental delay (OR, 1.8; 95% CI, 1.4, 2.4; P < .0001). CONCLUSIONS: Youth with DSD diagnosis have higher odds of a behavioral health or neurodevelopmental diagnosis compared with matched controls. Youth with CAH have higher odds of developmental delay, highlighting the need for screening in both groups.

Clinical phenotype and management of individuals with mosaic monosomy X with Y chromosome material stratified by genital phenotype.

Individuals mosaic for monosomy X and a cell line with Y chromosome material can have genitalia that appear phenotypical female, male, or ambiguous. Those with this karyotype and typical female genitalia are diagnosed with Turner syndrome; however, this definition specifically excludes those with genitalia other than typical female. There is limited information on whether medical and neurodevelopmental risks are similar among individuals with monosomy X and Y chromosome material across genital phenotypes. This multicenter retrospective study compared comorbidities and clinical management in individuals with monosomy X and Y material and male/ambiguous genitalia to those with typical female genitalia. Electronic medical records for all patients with monosomy X and Y material (n = 76) at two large U.S. pediatric centers were abstracted for predetermined data and outcomes. Logistic regression was used to compare the two phenotypic groups adjusting for site and duration of follow-up. The male/ambiguous genitalia group was just as likely to have congenital heart disease (RR 1.0, 95%CI [0.5-1.9]), autoimmune disease (RR 0.6 [0.2-1.3]), and neurodevelopmental disorders (RR 1.4 [0.8-1.2]) as those with female genitalia. Despite similar risks, they were less likely to receive screening and counseling. In conclusion, individuals with monosomy X and Y chromosome material have similar medical and neurodevelopmental risks relative to individuals with Turner syndrome regardless of genitalia, but there are notable differences in clinical management.

Distress Trajectories for Parents of Children With DSD: A Growth Mixture Model.

OBJECTIVE: This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions. METHODS: Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child's birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time. RESULTS: The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed "Resilient," "Recovery," "Chronic," "Escalating," and "Elevated Partial Recovery." Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the "Resilient" class (67.6%). CONCLUSIONS: This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories.

Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA.

Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had insufficient responses with a median GH peak of 3.7 ng/ml (range 1.1-8.6). Growth patterns revealed a drastic decline in length z-scores within the first year of life but then stabilized afterward. Five were treated with GH; one discontinued due to inconsolability. The other four participants continued on GH with improvement in linear growth velocity. Other endocrinopathies were identified in 7 of the 11 participants in this cohort. This study indicates that GH deficiency is associated with MCAP and that children with MCAP and hypoglycemia and/or postnatal growth failure should be evaluated for GH deficiency and other endocrinopathies.

Illness Uncertainty Longitudinally Predicts Distress Among Caregivers of Children Born With DSD.

OBJECTIVE: A subset of parents of children with disorders/differences of sex development (DSD) including ambiguous genitalia experience clinically elevated levels of anxious and depressive symptoms. Research indicates that uncertainty about their child's DSD is associated with parent psychosocial distress; however, previous studies have been cross-sectional or correlational in nature. The current study is the first to examine the longitudinal trajectory of the relationship between caregiver-perceived uncertainty about their child's DSD and caregiver anxious and depressive symptoms across the first 12 months following genital surgery in young children, or if surgery was not performed, the first 12 months following study entry. METHODS: One hundred and thirteen caregivers (Mage = 32.12; 57.5% mothers; 72.6% Caucasian) of children (N = 70; Mage = 9.81 months; 65.7% female) with DSD were recruited from 12 DSD specialty clinics in the United States. Caregivers completed psychosocial measures at baseline, 6 and 12 months following genitoplasty, or study entry if parents elected not to have surgery for their child. RESULTS: Caregiver illness uncertainty and both anxious and depressive symptoms were highest at baseline and decreased over time (ps < .05). Caregiver illness uncertainty predicted symptoms of anxious and depressive symptoms across all time points (ps < .05). CONCLUSIONS: Caregivers' perceptions of uncertainty about their child's DSD are highest soon after diagnosis, and uncertainty continues to predict both anxious and depressive symptoms across time. Thus, the initial diagnostic period is a critical time for psychological assessment and intervention, with parent illness uncertainty being an important clinical target.

Predictors of Psychosocial Distress in Parents of Young Children with Disorders of Sex Development.

PURPOSE: We evaluated demographic, financial and support predictors of distress for parents of young children with disorders of sex development including atypical genital development, and characterized early parental experiences. This work extends our previous findings to identify those parents at risk for distress. MATERIALS AND METHODS: Participants included mothers (76) and fathers (63) of a child (78) diagnosed with disorders of sex development characterized by moderate to severe genital atypia. Parents completed a demographic questionnaire, measures of anxious and depressive symptoms, quality of life, illness uncertainty and posttraumatic stress symptoms, and rated their satisfaction with the appearance of their child's genitalia. RESULTS: Depressive and posttraumatic stress symptoms of caregivers were comparable to standardized norms while levels of anxious symptoms were below norms. A subset of parents reported clinically elevated symptoms. Overall 26% of parents reported anxious symptoms, 24% reported depressive symptoms and 17% reported posttraumatic stress symptoms. Levels of illness uncertainty were lower than those of parents of children with other chronic illnesses. Differences by parent sex emerged, with mothers reporting greater distress. Lower income, increased medical care and travel expenses, and having no other children were related to increased psychosocial distress. CONCLUSIONS: Early psychosocial screening is recommended for parents of children with disorders of sex development. Clinicians should be aware that financial burden and lack of previous parenting experience are risk factors for distress.

Uncertainty and Posttraumatic Stress: Differences Between Mothers and Fathers of Infants with Disorders of Sex Development.

Parents of children with disorders of sex development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (Mage = 32.55 years, SD = 5.08) and 41 fathers (Mage = 35.53 years, SD = 6.78) of 53 infants (Mage = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents' psychosocial response to their child's diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.

Psychological Adjustment of Parents of Children Born with Atypical Genitalia 1 Year after Genitoplasty.

PURPOSE: We examined the psychological adjustment of parents of children born with moderate to severe genital atypia 12 months after their child underwent genitoplasty. MATERIALS AND METHODS: Parents were recruited longitudinally from a multicenter collaboration of 10 pediatric hospitals with specialty care for children with disorders/differences of sex development and/or congenital adrenal hyperplasia. Parents completed measures of depressive and anxious symptoms, illness uncertainty, quality of life, posttraumatic stress and decisional regret. RESULTS: Compared to levels of distress at baseline (before genitoplasty) and 6 months after genitoplasty, data from 25 mothers and 20 fathers indicated significant improvements in all psychological distress variables. However, a subset of parents continued endorsing clinically relevant distress. Some level of decisional regret was endorsed by 28% of parents, although the specific decision that caused regret was not specified. CONCLUSIONS: Overall the majority of parents were coping well 1 year after their child underwent genitoplasty. Level of decisional regret was related to having a bachelor's level of education, increased levels of illness uncertainty preoperatively and persistent illness uncertainty at 12 months after genitoplasty but was unrelated to postoperative complications.

Characterizing Early Psychosocial Functioning of Parents of Children with Moderate to Severe Genital Ambiguity due to Disorders of Sex Development.

PURPOSE: We examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes. MATERIALS AND METHODS: A total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised. RESULTS: A large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged. CONCLUSIONS: Although many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted.

Presentation to either the pediatric emergency department or primary care clinic for acute illness: the caregivers' perspective.

OBJECTIVES: This study aimed to understand and compare caregivers' perceptions of and attitudes toward care received in a primary care clinic (PCC) versus that received in the pediatric emergency department (PED) as well as the reasons for selecting either location to receive care for their child. METHODS: Surveys were administered to caregivers of children who receive their primary care at the same location who presented for a nonurgent sick visit to either the PCC or PED during regular PCC hours. RESULTS: One hundred fifty-one caregivers in the PCC and 83 in the PED completed the survey. Compared with caregivers who brought their child to the PED, those who presented to the PCC were more likely to report that the child had been sick for more than 2 days (P < 0.001), indicate that the child could wait more than 3 hours to be seen (P < 0.001), have called the PCC for advice (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9-9.2), have spoken with a nurse (OR, 3.7; 95% CI, 2.0-6.7), be satisfied with their phone call to the PCC (OR, 12.2; 95% CI, 6.4-23.1), and report that they could easily get in touch with the PCC (OR, 3.6; 95% CI, 1.8-7.3). Most caregivers who went to the PCC felt that it was more convenient (98.6%) and they would be seen more quickly (95.8%). CONCLUSIONS: Although all children had the same medical home, caregivers who presented to the PCC were more likely to have called the clinic, spoken with a nurse, and reported greater satisfaction with the PCC than those who brought their child to the PED.

Endometriosis in a Prepubertal Patient with 46,XY Difference in Sex Development: A Case Report.

INTRODUCTION: Endometriosis typically presents in postmenarchal patients with cyclic and acyclic pelvic pain. However, there are reports of endometriosis in premenarchal patients. CASE: We report a 10-year-old individual with 46,XY difference of sex development who was found to have endometriosis at the time of laparoscopic gonadectomy for gonadoblastoma. CONCLUSIONS: Although rare, endometriosis can occur in 46,XY individuals prior to puberty, highlighting the complex origin of the disease.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy.