bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Hip Bone Geometry in Transgender Adolescents Resembles the Experienced Gender if GnRHa Treatment Is Started in Early, but Not Late, Puberty
Authors: van der Loos Maria A T C , Hellinga Ilse , Vlot Mariska C , Klink Daniel T , Den Heijer Martin , Wiepjes Chantal M 
Published: May 2021

Abstract
Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender-affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin-releasing hormone agonist (GnRHa) and GAH prior to achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH at our center before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip Strength Analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual-energy X-ray absorptiometry scans performed at start of GnRHa and GAH treatments, and after ≥ 2 years of GAH treatment. Mixed model analyses were performed to study differences over time. Data were visually compared with reference values of the general population retrieved from the literature. A total of 322 participants were included, of whom 106 trans women and 216 trans men. In both trans women and trans men participants resembled the reference curve for SPW and ED of the experienced gender, but only when GnRHa was started during early puberty. Those who started during mid- and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one’s lifespan. Therefore, this study adds insights into sex-specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population.
Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review
Authors: Mao Jimmy J , Baker Jessica , Rainey William E , Young William F , Bancos Irina 
Published: May 2021

Abstract
Objective: The detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood. Our objectives were to investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management. Design: Retrospective case series from 2000–2020 at a single institution tertiary center; additional review of previously known cases before 2000 and from the medical literature. Patients and Measurements: Adult patients with concomitant PHEO and PA. Clinical, biochemical, radiologic, and histologic parameters were reviewed. Results: Fifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), but only 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients with preoperative work-up for catecholamine excess (14, 93%) were found to have elevated plasma or urinary metanephrines/catecholamines above the upper limit of normal. Adrenal vein sampling (AVS) was performed in 9 (60%) patients, where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. All patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy to treat their PHEO and/or PA. Postoperative catecholamines and/or catecholamine breakdown products normalized or improved in 13 (87%) patients and were not measured in 2. Recurrence of PHEO was not observed. Six (40%) displayed persistent PA postoperatively, where 4 required long-term mineralocorticoid blockade. Conclusions: Concomitant PHEO and PA is a rare but likely under-reported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be worked up for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.
Stability of Weekly Intramuscular Estradiol Cypionate in a Transgender Woman
Authors: Calzada Stephanie , Sarvaideo Jenna Lynne 
Published: May 2021

Abstract
Background: Transgender women often take estrogen with or without an antiandrogen to achieve the physical and physiological changes of estrogen. Estradiol may be administered through intramuscular (IM) injection weekly or every other week (1). It is thought that weekly IM estradiol may be more stable than every other week administration. The objective of this case was to evaluate the levels of IM estradiol cypionate when administered weekly.
Clinical Case: A 38-year-old transgender woman with a past medical history of gender dysphoria, type 2 diabetes mellitus, hyperlipidemia, obstructive sleep apnea compliant with continuous positive airway pressure, class 3 severe obesity, anxiety, depression and a non-smoker, presented for evaluation for hormone replacement therapy (HRT). The patient wished to begin IM estradiol because she heard it was most effective. She was started on estradiol cypionate 0.5 mL (2.5 mg) IM every Sunday along with spironolactone 100 mg daily. Approximately one month later, her estradiol was 65.8 pg/mL on a Saturday, total testosterone by LC-MS/MS was suppressed to 7 ng/dL (male: 300-1080 ng/dL, female: 9 - 55 ng/dL), FSH &lt;0.3 mIU/mL (1.5-12.4), LH &lt;0.3 mIU/mL (1.7-8.6). We increased her estradiol cypionate to 0.8 mL (4 mg) IM every Sunday to achieve goal estradiol levels up to 100-200 pg/mL. Approximately 2 months later, estradiol was up to 160 pg/mL on a Thursday. FSH and LH remained suppressed. Spironolactone was stopped. Patient gave her estradiol dose every Sunday between 4:15-7 PM. She injected on the lateral thigh switching sides every week. At the patient’s request, blood was drawn on distinct days of the week going further from the day of injection as data collection progressed. The data we received: Monday: 153 pg/mL, Tuesday: 164 pg/mL, Wednesday: 147 pg/mL, Thursday: 122 pg/mL, Friday: 134 pg/mL, Saturday: 167 pg/mL. All labs were drawn between approximately 9:30-10:15 AM.
Conclusion: Our patient wanted to see just how stable weekly IM estradiol cypionate was. We found she was able to stay within target physiologic estrogen levels, 100-200 pg/mL, throughout the week. Overall mean +/- standard deviation levels for the six samples taken between injections were 148 +/- 17 pg/mL (range: 122-167). This case provides reassurance to clinicians concerned IM estradiol may cause supraphysiologic estradiol levels.
References: 1. Wylie C Hembree et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 11, 1 November 2017, Pages 3869-3903, https://doi.org/10.1210/jc.2017-01658
The Role of the Endocrinologist in the Gender Adequacy Process and the Barriers for Adequate Transgender Health Care
Authors: Saliba Alexandra 
Published: May 2021

Abstract
The transgender universe comprises a wide range of individuals who do not identify with the gender role related to their birth sex, presenting distinct gender identities that transcend the binary concept of female and male. The follow-up of this population requires specific knowledge and training for its demands and peculiarities. Hormone therapy is a key point in the process of gender adequacy, and despite the increase in demand for specialized health services, there are still many barriers to full and free of prejudice health care. This is a descriptive and exploratory study about the characteristics of the professional training of the doctors involved in transgender health care, in particular the endocrinologist, and to enable an overview of the doctor-patient relationship and medical follow-up in the context of transsexuality in the Federal District. For this purpose, questionnaires were used for physicians: endocrinologists, family and community physicians, urologists, and psychiatrists; and transgender people residents of the Federal District. This study shows that most of the professionals involved in the process of gender adequacy, in particular the endocrinologist, do not present confidence or knowledge to accomplish it, and prejudice is still presented in a striking way in health care. In Federal District, services are not adequately structured for the care of this population, both from the perspective of doctors and transgender people. Moreover, in this sample, it was observed that the higher degree of specific knowledge in the subject increases the sensation of confidence of the professional to treat transgender people but does not correlate with the prejudice.
Hepatic Abnormalities in Youth With Turner Syndrome
Authors: Singh Isani , Noel Gillian , Barker Jennifer M , Chatfield Kathryn C , Khanna Amber D , Nokoff Natalie , Davis Shanlee M 
Published: May 2021

Abstract
Background: While cardiac complications, short stature, and infertility are often discussed in the context of Turner Syndrome (TS), abnormalities of liver function are less well described. In order to address this gap in knowledge, we sought to better characterize hepatic abnormalities in youth with TS. Methods: PEDSnet is a collaboration across 7 major US pediatric institutions that unifies electronic medical data including diagnoses, prescriptions, and laboratory measurements for over 6 million children. 2,145 females with a diagnosis of TS were matched to 8,580 females without TS (1:4 ratio) on site, race (68% White), ethnicity (15% Hispanic), payer source, year of birth, age at most recent visit (median 14 years), and duration of care (mean 8 years). Outcomes of interest included highest recorded liver enzyme values (AST and ALT) categorized as normal or above the upper limit of normal (ULN) defined as &gt;95th percentile for their age, and specific liver diagnoses. Proportions were compared between the cohorts using odds ratios (OR) and 95% confidence intervals (CI) from a generalized estimating equations approach. Multinomial logistic regression was conducted to investigate potential risk factors for liver abnormalities within the TS cohort. Results: Out of 1,159 girls with TS who had liver enzymes recorded in PEDSnet, 58% had at least one AST or ALT above the ULN. TS patients were more likely to have enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), more likely to be in the 2-3 times ULN category (OR: 2.7, 95% CI: 1.7-3.3), and more likely to be in the &gt;3 times ULN category (OR: 1.7, 95% CI: 1.3-2.2) compared to girls without TS. TS patients were also more likely to have any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), including significantly higher risk of 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 tumor/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In the multinomial model, age, BMI, and the presence of a thyroid condition, cardiovascular diagnosis, or diabetes significantly (p &lt; 0.05) increased the risk for elevated liver enzymes in girls with TS, while mosaicism, estrogen prescription, and celiac disease did not. Stratifying by age groups, over 40% of girls with TS had ALT elevations (24% &gt; 2 times ULN, some with diagnosed liver conditions) under age 10, when liver screening is officially recommended per TS guidelines. Conclusions: Prevalence of elevated liver enzymes and diagnoses of liver disease are significantly higher in youth with TS vs. controls, emphasizing the need for clinical monitoring and additional research. Given the high percentage of girls &lt;10 years of age with clinically significant liver enzyme elevation, there should be strong consideration for modifying the current guidelines to start screening earlier.
Cortisol Levels Is Associated With Left Ventricular Diastolic Dysfunction in Diabetic Patients
Authors: Sagara Rikako , Inoue Tomoaki , Sonoda Noriyuki , Yano Chieko , Motoya Misato , Umakoshi Hironobu , Sakamoto Ryuichi , Ogawa Yoshihiro 
Published: May 2021

Abstract
Introduction: Diabetes mellitus (DM) is a major cause of cardiovascular disease including heart failure with preserved ejection fraction (HFpEF), which is characterized by left ventricular diastolic dysfunction (LVDD). It is reported that Cushing’s syndrome is also associated with LVDD. The relationship between plasma cortisol concentration and LVDD, however, has not been investigated in patients with DM. Methods: In this study, 109 patients with DM and 104 patients with non-DM without overt heart failure were enrolled. Left ventricular function were assessed using echocardiography. The ratio of early diastolic velocity (E) from transmitral inflow to early diastolic velocity (e’) of tissue Doppler at mitral annulus (E/e’) was used as an index of diastolic function. Parameters of plasma cortisol concentration, glycemic control, lipid profile, treatment with anti-diabetic drugs and other clinical characteristics were evaluated, and their association with E/e’ determined. Patients taking steroids, undergoing dialysis treatment and with overt heart failure were excluded. Results: Univariate analysis showed that E/e’ was significantly correlated with age (p&lt;0.001), duration of diabetes (p=0.039), systolic blood pressure (SBP) (p&lt;0.001), eGFR (p=0.002), sodium glucose cotransporter 2 (SGLT2) inhibitor use (p&lt;0.001) and cortisol (p=0.009) in patients with DM. Multivariate linear regression analysis showed that log E/e’ was positively correlated with age (p=0.018), log SBP (p= 0.005), eGFR (p=0.015), cortisol (p=0.028) and that log E/e’ was inversely with inhibitor use (p=0.018). There was no association between E/e’ and cortisol in patients with non-DM. Conclusions: Cortisol may be important in the development of LVDD in patients with DM.
Understanding, Communication, Concerns and Repercussions of Sexual Development Differences by Mothers’ Perspectives
Authors: Lousada Lia Mesquita , Domenice Sorahia , Elaine Maria Frade Costa L , Bachega Tania A , Batista Rafael Loch , Fontenele Eveline Gadelha Pereira , Coutinho Debora Cabral , Carina Marques Barroso Barroso L , Geroldo Sandra Regina , Mendonca Berenice Bilharinho 
Published: May 2021

Abstract
Introduction: Differences of sexual development (DSD) define congenital diseases in which an atypical development of chromosomal, gonadal or anatomical sex occurs. The approach involves complex themes: gender designation, genitoplasty, hormonal treatment and fertility. Mothers’ understanding optimizes their children’s assistance. Objective/methods: To analyze the mothers’ understanding about the DSD condition, doubts, concerns, barriers to communication and repercussion in gender, sexual orientation and relationships in a cohort followed in reference centers in São Paulo (SP) and Ceará (CE), through an interview. Results: 112 mothers (72 from SP and 50 from CE) were interviewed. Mothers’ mean age was 35 y. The satisfaction related to the understanding about their children’s condition (on a scale from 1 to 5) was higher in the SP: medians of 4 (SP) and 3 (CE). Significant differences were evidenced between the numbers of mothers who knew the condition’s name, 56.3% (SP) and 38.6% (CE); who knew why the children had been affected by it, 38.5% (SP) and 16.7% (CE); and who knew the drugs’ function, 89.3% (SP) and 70.4% (CE). 70% to 83% of the mothers referred doubts, mainly related to the diagnosis and their feeling of guilt. Considering only children with atypical genitalia at birth (n:115), the difference was not diagnosed at hospital in 15% (4 from SP and 14 from CE). Pediatricians and obstetricians first communicated to mothers about the atypical genitalia in 73% of the reports. 70% (SP) and 41% (CE) of the mothers considered the first approach inappropriate. 89% of all mothers feel uncomfortable in talking to other people about the DSD condition and 68% experienced negative comments. Around 70% of mothers reported discomfort in exposing their children’s genitalia and 64% considered genitoplasty as an urgency. 47% referred that the DSD may influence the gender identity, 65.4% referred it may prejudice relationships and 33.3% believed it may influence on sexual orientation. The concern related to stigma was higher than related to fertility, genitalia appearance, relationships, treatments, gender identity and sexuality. Conclusion: Most of the mothers of DSD children, even in reference centers, showed unsatisfaction and lack of knowledge. The health team should be trained and the approach should consider the mothers’ perspectives and be appropriate to the cultural context. Educational actions may improve understanding and reduce the DSD stigma.
A Steroid Receptor Coactivator Stimulator MCB-613 Attenuates Adverse Remodeling After Myocardial Infarction
Authors: Mullany Lisa K , Rohira Aarti , Kim Jong H , Leach John P , Ortiz Andrea , Stork Brittany , York Brian L , Song Yongcheng , Dacso Clifford C , Lonard David M , Martin James F , O’Malley Bert W 
Published: May 2021

Abstract
Previous work from ours and other laboratories have shown that steroid receptor coactivators (SRCs) are involved in heart development and in mitigating cardiac dysfunction in cardiac injury models. Members of the p160 SRC family, SRC-1 (NCOA1), SRC-2 (NCOA2/TIF2/GRIP1) and SRC-3 (NCOA3/AIB1/ACTR/pCIP), interact with nuclear receptors and other transcription factors to drive target gene expression by assembling transcriptional coactivator complexes to increase transcription. This indicates a potential for SRC targeting drugs pertinent to cell migration, proliferation and survival-promoting paracrine interactions in cardiac tissue injury responses. We have identified a small molecule activator of SRCs (MCB-613) that selectively and reversibly binds to SRCs as shown by surface plasmon resonance and is a potent SRC stimulator that acts to greatly enhance SRC transcriptional activity with no apparent toxicity in mice. We postulated that MCB-613 could enable wound repair and preservation of cardiac function after an acute MI by reducing the extent of injury-related fibrosis and the subsequent chronic loss of cardiac function associated with non-contracting scar tissue. We thus tested the effect of MCB-613 on the cardiac injury response by administering MCB-613 two hours after ischemic injury in a mouse model of MI. Along with measurements of functional cardiac output and damage, we sought to identify the cell-type specific responses responsible for MCB-613’s cardio-protective effects by utilizing single cell transcriptomics of cardiac interstitial cells to characterize the effects of SRC stimulation on cardiac function post-MI. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post-MI, induces lasting protection from adverse remodeling concomitant with: (i) inhibition of macrophage inflammatory signaling and IL-1 signaling which attenuates the acute inflammatory response, (ii) attenuation of fibroblast differentiation, and (iii) promotion of Tsc22d3 expressing macrophages - all of which may limit inflammatory damage. Our results indicate MCB-613 controls the cellular interstitial cardiac repair response to ischemia. Distinct molecular and cellular mechanisms related to stimulation of SRC-3 have been identified that pave the way for the further exploration of SRCs as drug targets that can be engaged to improve the management of myocardial injury response outcomes. SRC stimulation with MCB-613 (and derivatives) is a potential novel therapeutic approach for inhibiting cardiac dysfunction after MI.
Improving the Diagnosis, Treatment, and Prevention of Endocrine Diseases Through Accurate and Reliable Laboratory Measurements With CDC Clinical Standardization Programs
Authors: Sugahara Otoe , Danilenko Uliana , Poynter Krista , Collins Lynn , Khoshnam Nasim , Buchannan Tatiana , Coffman Clark , Ribera Ashley , Laughlin Brandon , Dahya Komal , Smith Bianca , Dabbs-Brown Amonae , Pokuah Fidelia , Wirtz Douglas , Ulmer Candice Zena , Zhou Hui , Lyle Alicia , Zhang Li , Vesper Hubert W 
Published: May 2021

Abstract
Laboratory measurements are critical for correct diagnosis and treatment of patients with chronic diseases such as hypogonadism, PCOS, and thyroid diseases. Inaccurate measurements of disease biomarkers can lead to misclassification of patients/incorrect treatment and prevent the effective use of research findings in patient care. The CDC Clinical Standardization Programs (CDC CSP) improve the accuracy and reliability of clinical biomarker measurements by assessing and improving the analytical performance of assays. The CDC CSP assist with assay calibration, the certification of analytical performance, and the monitoring of routine patient and research testing. The CDC CSP work with clinical/research laboratories and assay manufacturers to improve laboratory measurements. Its current programs include the following analytes: total testosterone (TT), estradiol (E2), vitamin D (VD), free thyroxine (FT4), total cholesterol (TC), total glycerides (TG), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C). The work is being conducted through certification/monitoring programs and technical assistance. Most assays participating in the certification programs have seen performance improvements and maintain performance over time by continuous participation. Most major commercial laboratories and assays manufactures are enrolled in the certification programs. Currently certified and non-certified assays are available. Assays certified by CDC CSP are listed on the website at https://www.cdc.gov/labstandards/hs.html. The CDC Lipid Standardization Programs and CDC Accuracy-based Monitoring Programs allow for weekly monitoring of analytical performance of routine tests for analytes including TT, VD, TC, TG, HDL-C, apolipoprotein A1 and B. These monitoring programs assist researchers with assessing measurement accuracy of research studies over time and across laboratories. The CDC CSP also support accuracy-based external quality assurance surveys such as those offered by the College of American Pathologists (CAP). The CDC CSP assist researchers and stakeholders with developing and establishing reference intervals and conducting studies to better assess and diagnose patients. Based on the needs and requests from clinical community, programs for new biomarkers such as Lp(a), PTH and glucose are being developed. The CDC CSP work with stakeholders, such as the Endocrine Society and the Partnership for the Accurate Testing of Hormones, to educate the clinical and laboratory communities about the importance of using standardized assays in patient care, research, and public health.