Background: The association between fine particulate matter (PM2.5) and cardiovascular outcomes is well established. To evaluate whether source-specific PM2.5 is differentially associated with cardiovascular disease in New York City (NYC), we identified PM2.5 sources and examined the association between source-specific PM2.5 exposure and risk of hospitalization for myocardial infarction (MI). Methods: We adapted principal component pursuit (PCP), a dimensionality-reduction technique previously used in computer vision, as a novel pattern recognition method for environmental mixtures to apportion speciated PM2.5 to its sources. We used data from the NY Department of Health Statewide Planning and Research Cooperative System of daily city-wide counts of MI admissions (2007–2015). We examined associations between same-day, lag 1, and lag 2 source-specific PM2.5 exposure and MI admissions in a time-series analysis, using a quasi-Poisson regression model adjusting for potential confounders. Results: We identified four sources of PM2.5 pollution: crustal, salt, traffic, and regional and detected three single-species factors: cadmium, chromium, and barium. In adjusted models, we observed a 0.40% (95% confidence interval [CI]: –0.21, 1.01%) increase in MI admission rates per 1 μg/m3 increase in traffic PM2.5, a 0.44% (95% CI: –0.04, 0.93%) increase per 1 μg/m3 increase in crustal PM2.5, and a 1.34% (95% CI: –0.46, 3.17%) increase per 1 μg/m3 increase in chromium-related PM2.5, on average. Conclusions: In our NYC study, we identified traffic, crustal dust, and chromium PM2.5 as potentially relevant sources for cardiovascular disease. We also demonstrated the potential utility of PCP as a pattern recognition method for environmental mixtures.

Objective: To use magnetic resonance imaging (MRI) to quantify the follicle number per ovary (FNPO) using biplanar measurements and determine the ovarian volume (OV) using three-dimensional measurements in adolescents and young adults with polycystic ovary syndrome (PCOS) and controls and compare the differences between these groups; to examine the relationships between FNPO and OV and metabolic markers associated with PCOS; to compare OV obtained by use of MRI and ultrasound between young patients with PCOS and controls. Design: Cross-sectional study. Setting: Outpatient within a major medical center in New York City. Patients: Adolescent girls and young women aged 13-25 years with PCOS (n = 16) and body mass index-, age-, and ethnicity- comparable control subjects (n = 15). Interventions: None. Main Outcome Measures: The OV and FNPO by use of MRI, OV by use of transabdominal pelvic ultrasound, anthropometric measurements, and biochemical and hormonal evaluation. Results: The FNPO was higher in participants with PCOS (23.7 +/- 4.6 follicles) than in controls (15.2 +/- 4 follicles) when adjusted for menstrual age. The OV by use of ultrasound was higher in participants with PCOS (11.7 +/- 5.6 mL) than in controls (8.1 +/- 3.4 mL); however, OV by use of MRI did not differ between the groups. The OV by use of MRI and ultrasound correlated in participants with PCOS (r = 0.62) but not in controls. Conclusions: Our results are in line with prior studies showing that FNPO may be a more sensitive measure of polycystic ovary morphology than OV. The results of this study support the use of ovarian k , a promising diagnostic tool for PCOS, in young patients. (Fertil Steril Rep (R) 2022;3:102-9. (c) 2022 by American Society for Reproductive Medicine.)

BACKGROUND AND AIM: Environmental health (EH) researchers often aim to identify sources that drive potentially harmful environmental exposures. We have adapted Principal Component Pursuit (PCP), a robust dimensionality reduction algorithm, to pattern recognition in EH. PCP decomposes the exposure matrix into consistent patterns of chemical exposure while separately isolating unique or infrequent outlying exposure events. We further tailored PCP for EH by adding: (1) a non-negativity constraint to enhance interpretability of identified patterns, (2) procedures to accommodate missingness, and (3) a separate penalty for observations below the limit of detection. METHODS: We began with an exposure mixture of 21 dioxins, furans, and polychlorinated biphenyls (PCBs), collectively referred to as persistent organic pollutants (POPs), measured in 1,000 U.S. adults from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). We applied PCP to this mixture to identify exposure patterns and investigated the association between identified patterns and leukocyte telomere length (LTL), a biomarker associated with chronic disease. We used pattern scores from PCP in linear regression models to evaluate their association with LTL, adjusting for potential confounders. RESULTS:PCP identified four patterns representing the overall exposure matrix: pattern 1 was characterized by dioxins, pattern 2 by furans, pattern 3 by higher-weight PCBs, while pattern 4 was driven by lower-weight PCBs including two mono-ortho PCBs. In adjusted models, we observed no association between patterns 1, 2, or 3 and LTL. We observed on average a 0.017 (95% CI: 0.000, 0.034) unit increase in log-LTL per one standard deviation increase in the exposure profile described by pattern 4. CONCLUSIONS:PCP can serve as a useful and robust technique that can accommodate missing values and values below the limit of detection to identify exposure patterns that are amenable to public health messaging and research. KEYWORDS: Mixtures, Mixtures analysis, Chemical exposures, Environmental epidemiology

BACKGROUND AND AIM: The association between fine particulate matter (PM2.5) air pollution and cardiovascular outcomes is well-established. PM2.5 is a heterogeneous mixture of chemical constituents and its composition can vary by air pollution source. To evaluate whether PM2.5 from certain sources may be differentially associated with cardiovascular disease, we examined the association between same-day exposure to source-specific PM2.5 and risk of hospital admission for myocardial infarction (MI) in New York City (NYC). METHODS: We applied Absolute Principal Components Analysis to identify sources of PM2.5 pollution using data from three NYC monitors. We used data from the New York Department of Health Statewide Planning and Research Cooperative System on daily city-wide counts of MI admissions (2007–2015). We examined associations between same-day exposure to source-specific PM2.5 and MI admissions in a time-series analysis, using a quasi-Poisson regression model and adjusting for temperature, relative humidity, day of week, and seasonal and long-term time trends. RESULTS:We identified six sources of PM2.5 pollution: 1) traffic emissions, 2) salt, 3) crustal dust, 4) secondary/regional sulfate and nitrate, 5) road dust, and 6) industrial emissions. In adjusted models, an interquartile range (IQR) increase in PM2.5 from crustal dust was associated with a 0.68% increase in the rate of hospitalization for MI, on average (95% CI: 0.12, 1.25%). We observed a 1.01% (95% CI: -0.11, 2.16%) and a 0.62% (95%CI: -0.13, 1.36%) increase in MI admission rates per one IQR increase in traffic-related and regional PM2.5, respectively. We observed no association with PM2.5 from other sources. CONCLUSIONS:Identifying particularly toxic sources of PM2.5 can lead to maximally efficient policies. In our NYC study we identified crustal dust and traffic-related PM2.5 as potentially toxic sources for cardiovascular disease. KEYWORDS: Air pollution, Particle components, Particulate matter, Cardiovascular diseases, Mixtures analysis, Short-term exposure

25-hydroxy vitamin D (25 OHD) deficiency and secondary hyperparathyroidism have been seen after metabolic and bariatric surgery, but data are lacking on the bone health outcomes of adolescent sleeve gastrectomy (SG). The purpose of this study was to examine bone-related nutrition after SG, compared to laparoscopic adjustable gastric band (LAGB), and trend bone turnover markers following SG. This is an observational study of 197 adolescents who underwent LAGB (n = 98) or SG (n = 99). Bone health labs were collected at baseline and 6 and/or 12 months after LAGB or SG, with additional analysis of bone turnover markers in the SG group. Calcium and 25 OHD levels increased at 6 and 12 months after LAGB and SG, with no difference between the surgeries. Parathyroid hormone levels decreased only in the SG group. SG patients had increased osteocalcin and carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) at 6 and 12 months post-SG, although CTX decreased between 6 and 12 months. Excess weight loss at 6 months predicted the rise in CTX, but the changes in osteocalcin and CTX could not be attributed to 25 OHD deficiency, hypocalcemia or hyperparathyroidism. Patients had improved 25 OHD levels post-surgery, which may be secondary to stringent vitamin supplementation guidelines. However, there were marked increases in bone turnover markers following SG. More studies are needed to evaluate the effects of SG on adolescent bone health and to correlate the early changes in bone turnover with bone mineral density and fracture risk.

INTRODUCTION:Although growth hormone (GH) is essential for attainment of peak bone mass, bone health in prepubertal children with GH deficiency is not routinely evaluated. The objective of this study was to evaluate bone microarchitecture in GH-deficient (GHD) boys using high-resolution peripheral quantitative computed tomography (HR-pQCT).METHODS:Fifteen control and fifteen GHD, GH naïve pre-pubertal boys were recruited for a case-control study at a major academic center. Subjects with panhypopituitarism, chromosomal pathology, chronic steroids, or stimulant use were excluded. Volumetric bone mineral density (vBMD; total, cortical, and trabecular), bone geometry (total, cortical and trabecular cross-sectional area, cortical perimeter), bone microarchitecture, and estimated bone strength of the distal radius and tibia were assessed by HR-pQCT. Areal BMD and body composition were assessed by DXA. Insulin-like growth factor 1 (IGF-1), osteocalcin, C telopeptide, and P1NP levels were measured.RESULTS:GHD subjects had a significantly smaller cortical perimeter of the distal radius compared to controls (p < 0.001), with the difference in cortical perimeter persisting after adjusting for height z score, age, lean mass, and 25-hydroxyvitamin D level (p < 0.05).No significant differences were found in vBMD. No significant differences were found in microarchitecture, estimated strength, areal BMD, body composition, or bone turnover markers. Analysis showed significant positive correlations between IGF-1 levels and cortical parameters.DISCUSSION/CONCLUSIONS:Prepubertal GHD boys had deficits in bone geometry not evident with DXA. Larger prospective/longitudinal HR-pQCT studies are needed to determine the extent of these deficits, the need for routine bone evaluation, and the timing of GH replacement for prevention or restoration of these deficits.

Abstract Background: PCOS affects 5-15% of females of reproductive age and frequently manifests in adolescence. One of its diagnostic criteria is presence of polycystic ovary morphology (PCOM); however, this criterion is based on adult data obtained by transvaginal ultrasound thus may not be relevant to younger patients. AMH represents an alternative marker for PCOM as it is produced by preantral ovarian granulosa cells, which are increased in this condition. This study uses MRI, a noninvasive and accurate method, to determine FC and OV in young patients with PCOS and controls. Aims: 1. To determine if AMH is different in PCOS compared to controls; 2. To examine the relationship between AMH and FC and OV by MRI in PCOS and controls; 3. To determine the relationship between AMH and androgens and insulin resistance in PCOS and controls. Methods: Healthy nonobese adolescents and young adults with PCOS (n=12) and controls (n=12), (mean age 19.7 ± 3.2 years, BMI 23.1 ± 3.2 kg/m2) participated. Labs after an overnight fast included AMH, LH, FSH, estradiol, total and free testosterone, androstenedione, DHEAS, and a 2h OGTT with glucose and insulin levels. HOMA-IR and insulin area under the curve (iAUC) were calculated. Whole body dual-energy x-ray absorptiometry (DXA) scan for percentage body fat (%BF) and ovarian MRI for OV and FC were obtained. Results: Compared to controls, PCOS had higher AMH (10.7 ± 5.8 vs 5.0 ± 2.5 ng/mL. Reference range: 1.05-12.86 ng/mL), total and free testosterone, androstenedione and DHEAS (P<0.003 for all). HOMA-IR, iAUC , BMI and %BF were similar between the groups. AMH correlated with total testosterone (r=0.66, p<0.03) and to FC (r=0.88, p=0.0002), but not with free testosterone, androstenedione, DHEA-S, LH, HOMA-IR, iAUC or OV by MRI. Conclusions: In this small study of young and nonobese patients, AMH was higher in PCOS than controls and highly correlated with FC using ovarian MRI and to testosterone levels. These findings support the use of AMH as a minimally invasively additional marker to assist in the diagnosis of PCOS.

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.

Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders that affects females of reproductive age. The characteristic features of PCOS individually have opposing effects on bone mineral density (BMD); however, their cumulative effect on BMD has not been clearly defined. Adolescence and young adulthood span a crucial period in achieving peak bone mass. Thus, a better understanding of the impact of PCOS on BMD in this age group is needed. Objectives: To determine whether BMD is different between young females with PCOS and controls and to identify factors that influence BMD in this population. Methods: Data from four cross-sectional studies with a total of 170 females aged 12–25 years with PCOS (n = 123) and controls (n = 47) with a wide range of BMIs (18.7–53.4 kg/m2) were analyzed. Participants had fasting glucose, insulin, and free and total testosterone concentrations measured. HOMA-IR was calculated. Whole-body BMD was assessed by dual-energy X-ray absorptiometry. Multiple regression analysis for predicting BMD included PCOS status, menstrual age, obesity, HOMA-IR, and free testosterone. Results: HOMA-IR and total and free testosterone were significantly higher in PCOS compared to controls but there was no difference in BMD z-score between PCOS (0.8 ± 1.0) and controls (0.6 ± 1.0) (p = 0.36). Obesity (p = 0.03) and HOMA-IR (p = 0.02) were associated with BMD z-score. Conclusions: Obesity status and insulin resistance, but not PCOS status, were each independently associated with BMD in adolescents and young women who spanned a wide range of BMIs.

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.

Abstract Background: Polycystic ovary syndrome (PCOS) is a prevalent disease that impacts approximately 4-8% of the United States population. Bariatric surgery has been found to not only treat obesity but also reverse the symptoms associated with PCOS. The aim of this study was to investigate in adolescent girls with PCOS changes in glucose-insulin dynamics after significant weight loss and to determine how hyperandrogenism is influenced. We hypothesized that girls with PCOS would demonstrate improvements in glucose-insulin dynamics and hyperandrogenism after bariatric surgery. Methods: This study was a retrospective analysis of a longitudinal dataset with participants divided into two groups: 1) girls without PCOS (Ctrls), and 2) girls with PCOS (PCOS), as defined by the NIH criteria. Primary outcomes were HOMA-IR, Matsuda index, and oral disposition index (ODI) after oral glucose tolerance test. Data were analyzed by T-tests comparison of parameters at baseline, and changes in parameters at 6 and 12 months post-surgery between groups with p<0.05 as significant. Results: 71 girls (mean weight =128.0±20 kg, mean BMI=47.0 ±7.0 kg/m2) between the ages of 14.4 and 18.8 yrs were evaluated for PCOS. 28 met NIH criteria for the diagnosis of PCOS. Another, 14 were hyperandrogenic (total testosterone>50ng/dl and/or free testosterone >5.3 pg/ml) with regular menses. The remaining 29 had regular menses and normal androgen levels but were grouped with the 14 without irregular periods as the control group. Surgery occurred at a mean age of 16.9± 1.1yr. At 6m, 61 were available for analysis (25 with PCOS, and 36 Ctrl) while at 12m, 41 were available (11 with PCOS, 29 Ctrls). At baseline HOMA-IR was significantly higher in PCOS patients (3.6±2.3) compared to controls (2.51±1.71), p<.05, though weight was similar(127.7±18.7 kg vs 127.8±21.1kg). At 6m and 12 months post-surgery there were no significant differences between groups in the amount of change of the HOMA-IR (1.4±2.3 vs 0.68±1.86 ), and (2.3±2.3 vs 0.98±2.24 ). The Matsuda Index (4.8±4.5 vs 7.0±5.3) and ODI (9.3±20.8 vs7.8±11.4 ) both showed no significant difference between PCOS and Control patients at baseline with no significant change at 6month in either, though the Matsuda Index changed more significantly in the controls compared to the PCOS group (-6.0±12.4 vs -3.2±3.0, p<0.05) at 12 months Conclusion: Although there were improvements in the glucose/insulin indices for both PCOS and Control groups only a modest increase in insulin sensitivity was noted for the controls compared to PCOS at 12 months. Further studies to determine the relationship between insulin dynamics, cycling and hyperandrogenism are in process. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

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.

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.