Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia.

BACKGROUND: Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH. METHODS: In this phase 3 trial, we randomly assigned adults with CAH in a 2:1 ratio to receive crinecerfont or placebo for 24 weeks. Glucocorticoid treatment was maintained at a stable level for 4 weeks to evaluate androstenedione values, followed by glucocorticoid dose reduction and optimization over 20 weeks to achieve the lowest glucocorticoid dose that maintained androstenedione control (≤120% of the baseline value or within the reference range). The primary efficacy end point was the percent change in the daily glucocorticoid dose from baseline to week 24 with maintenance of androstenedione control. RESULTS: All 182 patients who underwent randomization (122 to the crinecerfont group and 60 to the placebo group) were included in the 24-week analysis, with imputation of missing values; 176 patients (97%) remained in the trial at week 24. The mean glucocorticoid dose at baseline was 17.6 mg per square meter of body-surface area per day of hydrocortisone equivalents; the mean androstenedione level was elevated at 620 ng per deciliter. At week 24, the change in the glucocorticoid dose (with androstenedione control) was -27.3% in the crinecerfont group and -10.3% in the placebo group (least-squares mean difference, -17.0 percentage points; P<0.001). A physiologic glucocorticoid dose (with androstenedione control) was reported in 63% of the patients in the crinecerfont group and in 18% in the placebo group (P<0.001). At week 4, androstenedione levels decreased with crinecerfont (-299 ng per deciliter) but increased with placebo (45.5 ng per deciliter) (least-squares mean difference, -345 ng per deciliter; P<0.001). Fatigue and headache were the most common adverse events in the two trial groups. CONCLUSIONS: Among patients with CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels. (Funded by Neurocrine Biosciences; CAHtalyst ClinicalTrials.gov number, NCT04490915.).

Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline. DESIGN: Systematic review and meta-analysis of the literature. PATIENTS: Women with PCOS and treatment with insulin sensitisers. MEASUREMENTS: Hormonal and clinical outcomes, as well as side effects. RESULTS: Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m2 ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations. CONCLUSIONS: Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.

45,X/46,XY mosaicism: Clinical manifestations and long term follow-up.

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy.

Combined oral contraceptive pill compared with no medical treatment in the management of polycystic ovary syndrome: A systematic review.

OBJECTIVE: As part of the update of the International Evidence-Based Guidelines for the Assessment and Management of polycystic ovary syndrome (PCOS), a systematic review was performed to inform evidence-based recommendations. DESIGN: Systematic review. Only randomised controlled trial were included. PATIENTS: Women with PCOS; the use of combined oral contraceptive pills (COCP) was compared with no medical treatment. MEASUREMENTS: Outcomes were designed in collaboration with clinical experts, researchers, and consumers. Critical outcomes included hirsutism, irregular cycles, quality of life, body mass index (BMI), and weight. RESULTS: 1660 publications were identified, but only four studies were included. No studies could be combined for meta-analysis. COCP treatment improved cycle regularity compared with no medical treatment (100% vs. 0%, with low certainty of evidence). COCP showed no difference in improvement of hirsutism or BMI compared with placebo or lifestyle; a lower weight after COCP compared with no treatment (mean difference [MD] -8.0 (95% confidence interval, CI -11.67); -4.33 kg); and improvement in quality of life (MD 1.2 [95% CI 0.96]; 1.44), but these results were all very low certainty of evidence. CONCLUSION: Results show that COCP benefit cycle regulation, but other benefits or potential adverse effects were only identified with very low certainty of evidence. The COCP is frontline medical treatment in PCOS, but this is still based on established efficacy in the broader general population. Our results show that research in PCOS is seriously lacking and should be prioritised to capture core reproductive, metabolic and psychological outcomes important in PCOS.

Testis formation in XX individuals resulting from novel pathogenic variants in Wilms' tumor 1 (WT1) gene.

Sex determination in mammals is governed by antagonistic interactions of two genetic pathways, imbalance in which may lead to disorders/differences of sex development (DSD) in human. Among 46,XX individuals with testicular DSD (TDSD) or ovotesticular DSD (OTDSD), testicular tissue is present in the gonad. Although the testis-determining gene SRY is present in many cases, the etiology is unknown in most SRY-negative patients. We performed exome sequencing on 78 individuals with 46,XX TDSD/OTDSD of unknown genetic etiology and identified seven (8.97%) with heterozygous variants affecting the fourth zinc finger (ZF4) of Wilms' tumor 1 (WT1) (p.Ser478Thrfs*17, p.Pro481Leufs*15, p.Lys491Glu, p.Arg495Gln [x3], p.Arg495Gly). The variants were de novo in six families (P = 4.4 × 10-6), and the incidence of WT1 variants in 46,XX DSD is enriched compared to control populations (P < 1.8 × 10-4). The introduction of ZF4 mutants into a human granulosa cell line resulted in up-regulation of endogenous Sertoli cell transcripts and Wt1Arg495Gly/Arg495Gly XX mice display masculinization of the fetal gonads. The phenotype could be explained by the ability of the mutated proteins to physically interact with and sequester a key pro-ovary factor ß-CATENIN, which may lead to up-regulation of testis-specific pathway. Our data show that unlike previous association of WT1 and 46,XY DSD, ZF4 variants of WT1 are a relatively common cause of 46,XX TDSD/OTDSD. This expands the spectrum of phenotypes associated with WT1 variants and shows that the WT1 protein affecting ZF4 can function as a protestis factor in an XX chromosomal context.

Testosterone-to-estradiol ratio and lung function in a prospective study of Puerto Rican youth.

BACKGROUND: Age- and sex-related differences in asthma may be due to changes in sex hormone levels. OBJECTIVE: To evaluate whether a change in free testosterone or free testosterone-to-estradiol ratio is associated with changes in lung function and eosinophils in the Puerto Rican youth. METHODS: We tested for the association between the change in sex hormone levels and change in lung function or change in eosinophils in a prospective study of 317 children (with and without asthma) followed up from ages 6 to 14 years to ages 10 to 20 years (146 females, 171 males) in San Juan, Puerto Rico. Serum levels of testosterone, estradiol, sex hormone-binding globulin, and progesterone were measured at 2 study visits, approximately 4.9 years apart. Using testosterone and sex hormone-binding globulin levels, we derived free testosterone and the free testosterone-to-estradiol ratio. Multivariable linear regression was used for the analysis of change in lung function and eosinophils, conducted separately by sex. RESULTS: In girls, each quartile increment in the free testosterone-to-estradiol ratio was associated with a 2.03% increment in percent predicted forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) between study visits. In males, each quartile increment in the free testosterone-to-estradiol ratio was associated with a 3.27% increment in percent predicted FEV1 and a 1.81% increment in percent predicted FEV1/FVC between study visits. In girls with asthma, an increased free testosterone-to-estradiol ratio was significantly associated with decreased eosinophils between visits (P=0.03). CONCLUSION: In Puerto Rican youth, increased free testosterone-to-estradiol ratio over time was associated with an increased FEV1/FVC in both sexes, and with an increased FEV1 in males.

Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.

SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P = 4.5 × 10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.

Adolescent polycystic ovary syndrome according to the international evidence-based guideline.

BACKGROUND: Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging because features of normal pubertal development overlap with adult diagnostic criteria. The international evidence-based PCOS Guideline aimed to promote accurate and timely diagnosis, to optimise consistent care, and to improve health outcomes for adolescents and women with PCOS. METHODS: International healthcare professionals, evidence synthesis teams and consumers informed the priorities, reviewed published data and synthesised the recommendations for the Guideline. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied to appraise the evidence quality and the feasibility, acceptability, cost, implementation and strength of the recommendations. RESULTS: This paper focuses on the specific adolescent PCOS Guideline recommendations. Specific criteria to improve diagnostic accuracy and avoid over diagnosis include: (1) irregular menstrual cycles defined according to years post-menarche; > 90 days for any one cycle (> 1 year post-menarche), cycles< 21 or > 45 days (> 1 to < 3 years post-menarche); cycles < 21 or > 35 days (> 3 years post-menarche) and primary amenorrhea by age 15 or > 3 years post-thelarche. Irregular menstrual cycles (< 1 year post-menarche) represent normal pubertal transition. (2) Hyperandrogenism defined as hirsutism, severe acne and/or biochemical hyperandrogenaemia confirmed using validated high-quality assays. (3) Pelvic ultrasound not recommended for diagnosis of PCOS within 8 years post menarche. (4) Anti-Müllerian hormone levels not recommended for PCOS diagnosis; and (5) exclusion of other disorders that mimic PCOS. For adolescents who have features of PCOS but do not meet diagnostic criteria an 'at risk' label can be considered with appropriate symptomatic treatment and regular re-evaluations. Menstrual cycle re-evaluation can occur over 3 years post menarche and where only menstrual irregularity or hyperandrogenism are present initially, evaluation with ultrasound can occur after 8 years post menarche. Screening for anxiety and depression is required and assessment of eating disorders warrants consideration. Available data endorse the benefits of healthy lifestyle interventions to prevent excess weight gain and should be recommended. For symptom management, the combined oral contraceptive pill and/or metformin may be beneficial. CONCLUSIONS: Extensive international engagement accompanied by rigorous processes honed both diagnostic criteria and treatment recommendations for PCOS during adolescence.

Curtailing PCOS.

Polycystic ovary syndrome (PCOS), characterized by hormonal imbalance and ovarian dysfunction, often starts during adolescence. Inconsistent diagnostic criteria, variable provider knowledge, and lack of consensus pose specific challenges for the care of women with PCOS. These factors encourage inaccurate diagnosis with both under and overdiagnosis. This unfavorable diagnostic experience exasperates affected women and limits timely opportunities for intervention to minimize associated comorbidities, especially during the transition from pediatric to adult care. Recognition of these issues in the care of adolescents and women with PCOS inspired the development of the International Evidence-Based PCOS Guidelines, which emphasize the prevention, screening, and treatment of PCOS across the reproductive lifespan. The Guidelines and accompanying meta-analyses focus on three major categories of associated comorbidities: (1) reproductive; (2) metabolic; and (3) psychological. With the exception of infertility, this article considers common manifestations and comorbidities associated with PCOS throughout the lifecycle. Healthy lifestyle interventions with prevention of excess weight gain comprise the primary intervention for all comorbidities. Hence, early identification of girls "at risk" for PCOS and those with PCOS is a priority. Extensive guidelines for provider and patient education aim to decrease the medical, psychosocial, and economic burdens attributable to PCOS and its associated comorbidities.

Update on adrenarche.

PURPOSE OF REVIEW: Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when dehydroepiandrosterone sulfate (DHEAS) concentrations increase. This review provides an update on adrenal steroidogenesis and the differential diagnosis of premature development of pubic hair. RECENT FINDINGS: The complexity of adrenal steroidogenesis has increased with recognition of the alternative 'backdoor pathway' and the 11-oxo-androgens pathways. Traditionally, sulfated steroids such as DHEAS have been considered to be inactive metabolites. Recent data suggest that intracellular sulfated steroids may function as tissue-specific intracrine hormones particularly in the tissues expressing steroid sulfatases such as ovaries, testes, and placenta. SUMMARY: The physiologic mechanisms governing the onset of adrenarche remain unclear. To date, no validated regulatory feedback mechanism has been identified for adrenal C19 steroid secretion. Available data indicate that for most children, premature adrenarche is a benign variation of development and a diagnosis of exclusion. Patients with premature adrenarche tend to have higher BMI values. Yet, despite greater knowledge about C19 steroids and zona reticularis function, much remains to be learned about adrenarche.

Effect of the combined oral contraceptive pill and/or metformin in the management of polycystic ovary syndrome: A systematic review with meta-analyses.

BACKGROUND: Polycystic ovary syndrome (PCOS) has a prevalence of 8%-13%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence-based guidelines are needed in PCOS management. This systematic review with meta-analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines. METHODS: Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta-analyses were conducted, where appropriate. RESULTS: Fifty-six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low-quality evidence in adolescents, meta-analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] -4.02 [-5.23, -2.81], P < 0.001); COCP was better than metformin for menstrual regulation (MD -0.19 [-0.25, -0.13], P < 0.00001). In low-quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], P = 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03). Combined oral contraceptive pill alone was better than the combination with an anti-androgen for BMI (MD -3.04 [-5.45, -0.64], P = 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI. CONCLUSIONS: This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti-androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI ≥ 25 kg/m2 . There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin.

The diagnosis and treatment of PCOS in adolescents: an update.

PURPOSE OF REVIEW: Polycystic ovary syndrome (PCOS) is often difficult to diagnose in adolescents. Recent recommendations and concepts regarding the diagnosis and treatment of PCOS in the adolescent girl are considered. RECENT FINDINGS: The diagnosis of PCOS in adolescents should be primarily based on clinical and biochemical signs of hyperandrogenism and presentation with irregular menses. Because of the similarity of normal pubertal development and features of PCOS, the diagnosis should be deferred until at least 2 years following menarche. For girls who do not fulfill the diagnostic criteria, the focus should be on treatment of symptoms. SUMMARY: PCOS is a complex, multifaceted disorder, and should be diagnosed and treated in adolescents after taking into consideration the patient's full diagnostic picture, metabolic risks, and individual concerns, to both avoid overdiagnosis but yet be able to provide early and meaningful interventions.

Early Bilateral Gonadoblastoma Associated With 45,X/46,XY Mosaicism: The Spectrum of Undifferentiated Gonadal Tissue and Gonadoblastoma in the First Months of Life.

45,X/46,XY mosaicism is one of a heterogenous group of congenital conditions known as differences (disorders) of sex development (DSD) that results in abnormal development of internal and external genitalia. Patients with DSD, particularly those with segments of the Y chromosome, are at increased risk for germ cell tumors including gonadoblastoma. Gonadoblastoma is a neoplasm comprised of a mixture of germ cells and elements resembling immature granulosa or Sertoli cells with or without Leydig cells or lutein-type cells in an ovarian type stroma. Gonadoblastoma has an increased prevalence of 15% to 40% in patients with 45,X/46,XY mosaicism and has been previously reported in patients as young as 5 months of age with that karyotype. Herein, we describe a 3-month-old child with 45,X/46,XY karyotype who was referred for the evaluation of asymmetric labia majora. Additional evaluation revealed left streak gonad and right dysplastic/dysgenetic testis. Both gonads contained foci of cells typical for gonadoblastoma as well as undifferentiated gonadal tissue, underscoring the potential for very early infantile gonadoblastoma and the spectrum of developmental anomalies associated with this karyotype.

Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region.

BACKGROUND: The XX male disorder of sex development (DSD) is a rare condition that is most commonly associated with the presence of the SRY gene on one of the X chromosomes due to unequal crossing-over between sex chromosomes during spermatogenesis. However, in about 20% of the XX male individuals, SRY is missing, although these persons have at least some testis differentiation. The genetic basis of genital ambiguity and the mechanisms triggering testis development in such patients remain unknown. METHODS: The proband with 46,XX SRY-negative testicular DSD was screened for point mutations by whole exome sequencing and CNVs using a high-resolution DSD gene-targeted and whole genome array comparative genomic hybridisation. The identified Xp21.2 genomic alteration was further characterised by direct sequencing of the breakpoint junctions and bioinformatics analysis. RESULTS: A unique, 80 kb microdeletion removing the regulatory sequences and the NR0B1 gene was detected by microarray analysis. This deletion disturbs the human-specific genomic architecture of the Xp21.2 dosage-sensitive sex (DSS) reversal region in the XX patient with male-appearing ambiguous genitalia and ovotestis. CONCLUSIONS: Duplication of the DSS region containing the MAGEB and NR0B1 genes has been implicated in testis repression and sex reversal. Identification of this microdeletion highlights the importance of genomic integrity in the regulation and interaction of sex determining genes during gonadal development.

Present Knowledge on the Etiology and Treatment of Adrenarche.

Premature adrenarche (PA) has been assumed to be a benign variant of normal pubertal development. Yet, current collective information suggests associations between PA and potential risks for development of polycystic ovary syndrome and adult diseases such as the metabolic syndrome. Adrenarche refers to the increased secretion of the adrenal androgen precursors DHEA, DHEAS, and androstenedione, which normally occurs in children at age 6-8 years. PA may be identified clinically by early pubarche, which is defined as the development of pubic or axillary hair before 8 years in girls or 9 years in boys. This paper will consider adrenal steroidogenesis, genetic markers, neurobiological changes, skeletal maturation, and associations with adult disorders. The differential diagnosis will be reviewed because PA remains a diagnosis of exclusion. Finally, synthesis of current knowledge regarding PA, suggestions for evaluation, management, and treatment are offered.

Familial deletion of the HOXA gene cluster associated with Hand-Foot-Genital syndrome and phenotypic variability.

Hand-Foot-Genital syndrome is a rare autosomal dominant condition characterized by distal limb anomalies and urogenital malformations. This disorder is associated with loss-of-function mutations in the HOXA13 gene. HOXA13 plays an important role in the development of distal limbs and lower genitourinary tract of the fetus. We report a novel familial 589 kb deletion in the 7p15.2 region identified in a male toddler and his mother. The proband had severe penoscrotal hypospadias, mild skeletal anomalies of the hands and feet, cardiac, renal, and gastrointestinal anomalies. His mother had a bicornuate uterus, cervical incompetence, and minor anomalies of her hands and feet. This family was found to have the smallest reported deletion of 7p15.2 to date, and presented with features typical of Hand-Foot-Genital syndrome in the mother, but much more severe phenotype in her son. This deletion included the entire HOXA cluster in addition to the SKAP2 and EVX1 genes. An RT-PCR analysis was performed to determine the expression of the HOXA genes in the proband and to explore a parent-of-origin effect. Our expression studies did not support the hypothesis of an imprinted status of the HOXA2, HOXA3, HOXA5, and HOXA11 genes in peripheral blood. To our knowledge, this is the first familial 7p15.2 deletion. This family raises possibility for sexual dimorphism as a mechanism for phenotypic variability in patients with the HOXA gene cluster deletions. © 2016 Wiley Periodicals, Inc.

Pericarditis as the Presenting Feature of Graves Disease in a Pediatric Patient.

Pericarditis is a rare presentation of thyrotoxicosis associated with Graves disease. This association has not been previously described in the pediatric literature. We report a 17-year-old male patient who presented with chest pain, dyspnea, and tachycardia. He was found to have diffuse ST-segment elevation consistent with pericarditis. At presentation, he was noted to have bilateral proptosis. Abnormal thyroid function studies and an elevated thyroid-stimulating hormone receptor antibody level confirmed the diagnosis of Graves thyrotoxicosis. The patient was treated with anti-inflammatory and antithyroid agents and improved in time. We discuss previously reported cases of Graves disease-associated pericarditis in adults, potential etiologies, and management strategies.

PHYSICIANS' SELF-PERCEPTIONS OF CARE FOR EMERGING ADULTS WITH TYPE 1 DIABETES.

OBJECTIVE: Establishing care with adult providers is essential for emerging adults with type 1 diabetes (T1D) transitioning from pediatric care. Although research evaluating the transition from pediatric to adult care has been focused primarily on patients' perceptions, little is known about the adult providers' perspectives. We sought to ascertain adult providers' perspectives of caring for the medical and psychosocial needs of this patient population. METHODS: We developed and mailed a survey to 79 regional adult endocrinologists and 186 primary care physicians (PCPs) identified through 2 regional insurance plans. Questions addressed perceived aptitude in clinical aspects of diabetes management, importance and availability of diabetes team members, and opinions regarding recommended transition methods. RESULTS: The response rate was 43% for endocrinologists and 13% for PCPs. Endocrinologists reported higher aptitude in insulin management (P<.01). PCPs reported greater aptitude in screening and treating depression (P<0.01). Although endocrinologists and PCPs did not differ in their views of the importance of care by a comprehensive team, endocrinologists reported better access to diabetes educators and dieticians than PCPs (P<.01). Recommended transition methods were described as useful. CONCLUSION: These preliminary results suggest that endocrinologists are better prepared to assume diabetes care of emerging adults, whereas PCPs may be better prepared to screen and treat associated depression. Future studies are needed to determine if a medical home model with cooperative management improves care for emerging adults with T1D.