bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU233 Reduction Of Overutilization Of 1,25-Dihydroxyvitamin D
Authors: Brown Jeremy , Dewan Maya , Courter Joshua , Spooner Andrew , Treasure Jennifer , Kaplan Kyle , Crimmins Nancy Abigail 
Published: October 2023

Abstract
Disclosure: J. Brown: None. M. Dewan: None. J. Courter: None. A. Spooner: None. J. Treasure: None. K. Kaplan: None. N.A. Crimmins: None.
Unnecessary testing may lead to patient harm, inappropriate treatments, and/or increased cost. Per the Endocrine Society, in conjunction with Choosing Wisely, 1,25-dihydroxyvitamin D (1,25-OH D) should not be measured unless a patient has hypercalcemia or decreased kidney function. This study sought to evaluate overutilization of 1,25-OH D at Cincinnati Children's Hospital Medical Center. We queried EPIC for all 1,25 OH vitamin D tests drawn in all patients (inpatient and outpatient) between 01/01/2021 and 12/31/2021. We then cross-referenced each test with all patient ICD10 codes associated with each patient’s chart. Appropriate ordering was defined as the patient having an ICD10 code related to calcium disorders or renal disease (531 codes included, data not shown). Out of a total of 1,057 1,25-OH D tests ordered, we found that only 19.4 percent were in patients whose chart contained a code that clinically would indicate testing. Further analysis showed most of these tests were obtained by psychiatry (22.7%) and community general pediatricians (14.6%) and not by endocrinology (12.5%) or nephrology (2.2%) providers. We will use this as baseline data to design quality improvement interventions to reduce unnecessary ordering of 1,25 OH vitamin D, including an ordering pathway in Epic to provide point of care education and guidance regarding appropriate Vitamin D test selection. In summary, inappropriate ordering of 1,25 vitamin D is common, likely due to misunderstanding of the best test to determine vitamin D sufficiency.
Presentation: Thursday, June 15, 2023
THU621 Mifepristone In Exogenous Cushing's Syndrome
Authors: Priyadarshan Swetha , Blavo Delali Ohui 
Published: October 2023

Abstract
Disclosure: S. Priyadarshan: None. D.O. Blavo: None.
Introduction: Cushing’s syndrome is characterized by elevated cortisol levels in the body and is associated with significant morbidity and mortality. It can be broadly divided into endogenous and exogenous Cushing’s depending on etiology. Endogenous (body-produced) Cushing’s is diagnosed using Late Night Salivary Cortisol(LNSC), Dexamethasone Suppression Test(DST), or 24-hr Urinary-Free Cortisol(UFC) and after ruling out exogenous glucocorticoid administration. Hyperglycemia and weight gain are two of the many manifestations of Cushing’s that have hitherto proven to be a challenge to treat. Mifepristone is a glucocorticoid receptor antagonist that was recently FDA-approved for treating endogenous Cushing’s syndrome following the breakthrough SEISMIC trial. Literature regarding the utility of Mifepristone in exogenous Cushing’s has been limited since its approval. This case aims to fill that void. Case: A 35-year-old female with past medical history of rheumatoid arthritis was referred to endocrinology for further evaluation due to complaints of weight gain, dorso-cervical fat pad, abdominal striae, bruising of her right breast, and hirsutism requiring her to shave twice a week. She had previously been on prednisone 10mg-20mg daily for 2-3years for rheumatoid arthritis and was later weaned off due to her developing bruising, perioral abscess and dorsocervical fat pad. She was hospitalized for pneumonia later that year and discharged with dexamethasone. Her baseline weight at the time had been around 380lbs and she had a rapid weight gain over the next few weeks with a peak of 467lbs, associated with facial swelling and shortness of breath. For this, a DST was done per her primary provider among other labs and showed a cortisol level of 0.5mcg/dL(n&lt;2mcg/dL). At the endocrine clinic, she had an extensive workup done including renin, aldosterone, plasma metanephrines, LH/FSH levels which all returned within normal limits. A1c was elevated at 6.7%(n &lt;5.7%) and she was started on Metformin 1000mg BID. She had a repeat DST which suppressed cortisol appropriately however her midnight salivary cortisol was elevated. She was diagnosed with exogenous Cushing’s syndrome and started treatment with Mifepristone at 300mg daily. Her only side effect was mild nausea that later resolved. In 4 months, she had already lost 50lbs since her initial visit and HbA1c was down to 5.8. The dose was subsequently increased in increments up to 1200mg. In 7 months since starting Mifepristone, her weight was down to 312lbs, a total of 164lbs down from her initial weight. Her HbA1C was 4.6, down from her initial value of 6.7. Conclusion: This case is an excellent example of the effectiveness of Mifepristone in achieving glycemic control and weight reduction in Cushing’s syndrome with minimal side effects. More specifically, it serves to illustrate its utility in exogenous Cushing’s syndrome.
Presentation: Thursday, June 15, 2023
OR21-05 Low-dose Infigratinib, An Oral Selective Fibroblast Growth Factor Receptor (FGFR) Tyrosine Kinase Inhibitor, Demonstrates Activity In Murine Models Of Achondroplasia And Hypochondroplasia
Authors: Muslimova Elena , Demuynck Benoit , Loisay Léa , Paull Morgan , Legeai-Mallet Laurence 
Published: October 2023

Abstract
Disclosure: E. Muslimova: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. B. Demuynck: None. L. Loisay: None. M. Paull: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. L. Legeai-Mallet: None.
Background: FGFR3 is a negative regulator of bone growth and gain-of-function mutations in the FGFR3 gene result in different skeletal osteochondrodysplasias, including achondroplasia (ACH) and hypochondroplasia (HCH). ACH is the most common form of rhizomelic short stature, affecting between 1 in 15,000 and 1 in 30,000 live births worldwide. The incidence of HCH is thought to be approximately the same as ACH. Currently, there is only one approved therapy for ACH and no approved therapies for HCH. Previously we demonstrated that the oral, selective FGFR 1-3 tyrosine kinase inhibitor (TKI) infigratinib has preclinical activity in a mouse model mimicking ACH (Fgfr3Y367C/+). We hypothesized that infigratinib could improve defective endochondral ossification and ameliorate the phenotype in a mouse model of HCH (Fgfr3N534K/+), which is the first and only HCH mouse model that expresses the most frequent human heterozygous mutation p.Asn540Lys.Methods:Fgfr3N534K/+ mice were given subcutaneous injections of infigratinib or vehicle control every 3 days (1 mg/kg) or daily (1 mg/kg) for 15 days (post-natal day [PND] 4-19) or 21 days (PND 3-24), respectively. Results:Fgfr3N534K/+ mice treated with 1 mg/kg infigratinib daily for a total of 21 days showed a statistically significant increase in appendicular and axial skeleton (tibia +3.18%, femur +3.16%, humerus +3.04%, ulna +2.94%, radius +3.01%). Treatment with infigratinib modified skull shape, length of the mandible, and foramen magnum length (+3.72%). Cartilage growth plate organization, in particular the hypertrophic chondrocyte area, was modified, indicating that chondrocyte differentiation is improved. These results, although of a lower magnitude, are in line with those previously reported from the Fgfr3Y367C/+ mouse model of ACH, which showed a statistically significant improvement in upper limbs (humerus +7.3%, ulna +11.1%, radius +14.2 %), lower limbs (femur +10.4%, tibia +16.8%), and foramen magnum length (+3.76%), when infigratinib was administered at a dose of 0.5 mg/kg. Conclusions: Low-dose treatment with infigratinib in the Fgfr3N534K/+ HCH mouse model ameliorated the clinical hallmarks of human pathology and significantly lengthened the axial skeleton, the appendicular skeleton and improved foramen magnum length. Development of infigratinib in ACH is currently ongoing. These latest findings with infigratinib in this mouse model of HCH support the rationale for targeting FGFR3 with a specific TKI such as infigratinib for the treatment of children with HCH.
Presentation: Saturday, June 17, 2023
THU626 Impact Of Body Mass Index On Clinical And Endocrinological Characteristics Of Indian PCOS Population
Authors: Pandey Seema , Ojha Kamal , Jayprakasan Kanna , Khanduri Kanishk 
Published: October 2023

Abstract
Disclosure: S. Pandey: None. K. Ojha: None. K. Jayprakasan: None. K. Khanduri: None.
The prevalence of polycystic ovarian syndrome (PCOS), defined based on the Rotterdam criteria, in Indian women is about 10% and the clinical characteristics can be different compared to western PCOS population. The objectives of this study are to evaluate the baseline clinical characteristics of PCOS women and to compare the characteristics in different population categorised based on body mass index (BMI). Material & Methods: In this observational study done at a tertiary fertility unit in Northern India, all PCOS women, defined based on the Rotterdam criteria, attended the clinic during 2018-2022 were included (n=554). Women with known endocrine issues were excluded. The baseline characteristics - age, BMI, blood pressure (BP), hirsutism assessed by Ferriman-Galleway (FG) score, acanthosis nigricans, AMH, prolactin, TSH- were assessed. Results: While the mean (±standard deviation) age of patients the study population was found to be 27.2 ±4.1 years, the mean BMI was 25.8±4.4 Kg/m2 and Acanthosis nigricans was observed in 87 (17.51%) women. The mean B.P. was 116/76 (±9/8) mmHg and the mean FG score was 3±1. The mean AMH, TSH and prolactin were 7.26±4.39ng/mL, 3.42±5.21mIU/mL and 17.07±15.92ng/mL respectively. BMI was classified in four categories- ≤22.9 (normal, n=121), 23-24.99 (overweight, n=111), 25-29.99 (pre-obese, n=182) and ≥30.0 (obese, n=76). The mean age across the four BMI groups were 26.1±3.9, 27.5±3.9, 27.2±4.2 and 29.0±4.0 years respectively (P&lt;.001). The BP increases as the BMI increases (114/74 (±8/8), 116/76 (±8/8), 117/76 (±9/8) & 120/77 (±11/8) Kg/m2 respectively; P= &lt;0.05). There was no difference in FG scores across the four BMI groups (3±1, 3±1, 3±2, 3±2, respectively; P=0.8). While the AMH (7.42±4.66, 6.99±4.30, 7.49±4.43, 6.87±3.95ng/mL, respectively; P=0.644) and prolactin (17.38±19.02, 17.84±14.92, 17.55±16.22, 14.27±9.62ng/mL, respectively; P=0.42) were similar across the four BMI groups, the TSH tend to be higher in the higher BMI groups (2.77±1.70, 3.09±1.93, 3.45±4.07, 4.88±11.23mIU/mL respectively; P=0.038). The prevalence of Acanthosis nigricans (12(9.4%), 20(18%), 29 (15.9%), 26 (34.2%), respectively; P=&lt;0.001) was also found higher in the higher BMI groups. After conducting post-hoc analysis, it was found out that obese (≥30) group has highest mean of TSH (4.88±11.23) level, Age (28.97±4.04), B.P. count (120/77 (±11/±8)) and prevalence of acanthosis nigricans (34.2%). Discussion-While the mean (±SD) age of the study population was 27±4.1 years, the mean BMI was 25±4 Kg/m2. When categorized based on BMI (n=182; 32.9%) fell into the pre-obese group. While BMI showed a positive correlation with age, B.P., TSH and Acanthosis nigricans, nevertheless, the mean AMH, prolactin and FG score were similar across the 4 BMI groups.
Presentation: Thursday, June 15, 2023
THU628 Causal Relationship Between The Menstrual Cycle Length And Basal Metabolic Rate: A Two-sample Mendelian Randomization Study
Authors: Kazemi Maryam , Parry Stephen A 
Published: October 2023

Abstract
Disclosure: M. Kazemi: None. S.A. Parry: None.
Long or irregular menstrual cycles, as a hallmark reproductive trait in polycystic ovary syndrome (PCOS), have been associated with aberrant energy expenditure, obesity, and cardiometabolic comorbidities. However, current observational studies addressing the contributions of energy expenditure to menstrual cyclicity have generated conflicting results and have not utilized the full extent of known single nucleotide polymorphisms associated with basal energy expenditure. Whether the relationship is causal is uncertain. We conducted a two-sample Mendelian Randomization study to interrogate the causal relationships between basal metabolic rate and length of menstrual cycles. The (MR) analyses were performed using publicly released genome-wide association studies (GWAS) statistics from 2 separate European cohorts using the UK Biobank database. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), to detect and correct the effect of horizontal pleiotropy. The result of the IVM method revealed that genetically determined basal metabolic rate has an inverse causal effect on the length of the menstrual cycle (β, -0.13, SE, 0.03; P=2.17 E-05). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Sensitivity analyses revealed that horizontal pleiotropy was unlikely to distort the causal estimates. Collectively, our MR analysis revealed that basal metabolic rate appears to be causally affecting the length of menstrual cycles. Our findings reflect novel insights into the role of energy metabolism on menstrual disturbances. However, the molecular mechanisms should be investigated. Future MR analysis is warranted to confirm our findings by controlling for potentially relevant confounders, including obesity and age. Nevertheless, our findings have perturbations to elucidate causal pathways explaining obesity in relevant conditions, including PCOS.
Presentation: Thursday, June 15, 2023
THU639 17α-Estradiol Signals Primarily Through Nongenomic Mechanisms: Implications For Its Beneficial Longevity Effects
Authors: Cooke Paul S , Sirohi Vijay K , Zomer Helena D , Graceli Jones B , Mesa Ana , Medrano Theresa 
Published: October 2023

Abstract
Disclosure: P.S. Cooke: None. V.K. Sirohi: None. H.D. Zomer: None. J.B. Graceli: None. A. Mesa: None. T. Medrano: None.
Recent work indicates that exogenous 17α-estradiol (17α-E2), a stereoisomer of 17β-E2, increases longevity 20% in male mice, despite previous literature that 17α-E2 is a weak estrogen with low affinity for nuclear (n)ESR1. This study aimed to obtain mechanistic insights into uterine 17α-E2 actions in vivo. We hypothesized that 17α-E2 signals preferentially through membrane (m)ESR1 to affect target tissues and promote longevity. To test this, we treated pre-pubertal (postnatal day 20) female CD-1 mice with 3 daily ip injections of vehicle or 10 mg/kg of 17α-E2 or 17β-E2. 17α-E2 treatment did not significantly increase uterine weight - a marker of nuclear (n)ESR1 signaling (20.3 ± 2.1 vs. vehicle 15.7 ± 2.0, p&gt;0.05, n=4), while 17β-E2 strongly increased it to 41.4 + 1.1 mg; p&lt;0.05). Accordingly, histological analysis revealed reduced cell proliferation in 17α-E2- vs. 17β-E2-treated uteri. Both 17α-E2 and 17β-E2 produced robust and similar epithelial p-ERK and p-AKT expression, the active phosphorylated forms of these protein kinases. Western blotting and immunofluorescence showed that 17α-E2 and 17β-E2 stimulated a strong and comparable stimulation of EZH2, a critical mediator of estrogen’s epigenetic effects linked to mESR1 signaling, as well as increases in NRF2 and CBP signaling. Progesterone pre-treatment blocks both the 17α-E2- and 17β-E2-mediated increases in p-ERK. In conclusion, despite limited actions through nESR1, 17α-E2 robustly signals through mESR1 to activate uterine protein kinase cascades and epigenetic effects. Thus, 17α-E2 acts preferentially through mESR1, which may explain its powerful longevity effects despite limited effects on classical markers of estrogen action such as uterine weight.
Presentation: Thursday, June 15, 2023
THU641 Single-cell Transcriptomic Analysis Reveal Dysregulated Immune Modulation In The Pituitaries Of Letrozole-induced Mouse Model Of PCOS
Authors: De Robles Gabriela 
Published: October 2023

Abstract
Disclosure: G. De Robles: None.
The most common endocrine disorder, affecting both the reproduction and metabolism of females, is polycystic ovary syndrome (PCOS). Characterizations of the heterogeneous disorder include anovulation, biochemical hyperandrogenemia, insulin resistance, and obesity, which can be recapitulated with a letrozole-induced PCOS mouse model. Immune abnormalities have also been reported in PCOS human patients, including pro-inflammatory factor secretion imbalance and endothelial cell dysfunction. The extent to which the letrozole-induced mouse model for PCOS can represent these immune dysregulations remain unclear, specifically its relevance to disrupting hormone-regulating centers, such as the pituitary gland. Using a PCOS mouse model developed via letrozole induction, we performed single-cell mRNA sequencing on the pituitaries to study impairment in hormone activity and immune regulation. We also carried out a multiplexed immunoassay on stimulated splenocytes to profile cytokines under different immune cell activations. We identified B cells, neutrophils, microglia, T memory cells, and interestingly, sub-populations of macrophages in the pituitary. Differential expression analysis revealed affected genes in the total macrophages of PCOS mice, such as the up-regulation of Pf4, Il1a, and Ccl7. Differentially expressed genes, such as Lyz2, Ctss, Apoe, and H2-Aa, were also down-regulated in the T memory cells of PCOS mice. Pituitary cell types also exhibited dysregulated expressions, including lactotropes, corticotropes, gonadotropes, and somatotropes. Differences in cytokine expression from the multiplex immunoassays also allowed the mice to be distinct from those treated with letrozole or not via principal component analysis. Altogether, the letrozole-treated mice presented disrupted immune responses and hormonal imbalances in their transcription and cytokine profiles that further strengthens their ability to model PCOS.
Presentation: Thursday, June 15, 2023
FRI373 Effect Of Neonatal R115866 Injection On Ovary Development In Mice
Authors: Akroush Mike , Urbanowski Audrey , Edwards Abigail , Kipp Jingjing 
Published: October 2023

Abstract
Disclosure: M. Akroush: None. A. Urbanowski: None. A. Edwards: None. J. Kipp: None.
The active metabolite of vitamin A, retinoic acid, is vital to several physiological functions and is most notably associated with vision and organ development. Its role in the male reproductive system is well understood, but studies on female reproduction are lacking. Recent studies show that Cyp26b1, a retinoic acid degrading enzyme, is expressed highly in the day 1-10 mouse ovary. This time point correlates with the establishment of the primordial follicle pool. In vitro studies show that both retinoic acid and R115866, a Cyp26b1 inhibitor that blocks retinoic acid metabolism, increase cell proliferation. Therefore, we hypothesize that retinoic acid plays a critical role in the early development of the ovary. To test this hypothesis, we injected neonatal mice with R115866 at either 0.5 or 1.0 mg/kg during the first 7 days after birth when the levels of Cyp26b1 expression are high. At day 19, week 7, and week 15, ovaries were harvested for morphological, immunohistochemical, and RT-PCR studies. Our results showed that animals injected with R115866 showed dose-dependent decreases in body weight in day 19 and week 7 mice, while week 15 mice appeared to recover. Neonatal R115866 injection increased the number of multi-nucleic oocytes at day 19 and bursa cysts at week 15. Cyp26b1 mRNA and protein levels were both increased by R115866 treatment in Day 19 ovaries, as confirmed by real-time RT PCR and immunohistochemical studies, consistent with the effect of these inhibitors in increasing RA levels which in turn induce Cyp26b1 expression. Neonatal R115866 injection also increased the expression of proliferative markers, including Ki67, Cyclin E1, and PCNA. Currently, we are completing studies on follicle classification and count. Overall, our results suggest that retinoic acid plays an important role in the development of the mouse ovary and that balanced retinoic acid levels in early development are needed for the health of ovaries.
Presentation: Friday, June 16, 2023
FRI406 Maternal Biomarkers Of Adiposity And Stress For Preterm Birth
Authors: Mayne Gabriella , DeWitt Peter E , Wen Jennifer , Christians Uwe , Dabelea Dana , Schulkin Jay , Joseph Hurt K 
Published: October 2023

Abstract
Disclosure: G. Mayne: None. P.E. DeWitt: None. J. Wen: None. U. Christians: None. D. Dabelea: None. J. Schulkin: None. K. Hurt: None.
Background: Adiponectin is a potent uterine tocolytic and decreases with gestational age, so it could be a maternal metabolic quiescence factor during pregnancy. Maternal stress can influence risk for preterm birth, and adiponectin may be inversely related to cortisol. Therefore, we characterized a potential mechanistic link between preterm birth, adiponectin, and cortisol. In this pilot study, we hypothesized maternal plasma adiponectin and cortisol concentrations are inversely related and that lower adiponectin and higher cortisol associate with spontaneous preterm birth. Methods: We performed a nested case-control study using biobank morning fasting plasma samples, taken twice in pregnancy for the Healthy Start pre-birth cohort. We included low-risk women with singleton pregnancies and excluded mothers with major medical illness, preeclampsia, chronic hypertension, or prior preterm birth. We matched preterm cases with term controls (1:3) by gestational age at first blood sample and least variation in time between blood samples (16 preterm, 46 term). We quantified high (HMW), low molecular weight (LMW), and total adiponectin using an ELISA assay. We also quantified cortisol and five related steroid hormones from the same specimens using HPLC/mass spectrometry. We used generalized estimating equations and additive models to compare group means and associations between adiponectin and cortisol. We used machine learning with gradient boosting for predictive modeling. Results: Contrary to our hypothesis, total, HMW, and LMW adiponectin positively associated with cortisol across gestation (P&lt;0.001 for all), however the association was reduced in the preterm compared with term group and significantly so for LMW (P=0.044). In predictive modelling, HMW adiponectin, maternal pre-pregnancy BMI, maternal age, and cortisol were the four most highly relevant predictors for preterm birth (AUROC=0.704). Conclusion: In healthy low-risk patients, we found associations between adiponectin and cortisol differ across gestation for pregnancies ending with term or preterm delivery and have some predictive value in this cohort. This suggests a possible mechanistic link between maternal metabolism and stress for pregnancy maintenance. These biomarkers may prove useful as predictors in larger studies and might indicate possible maternal metabolic therapies for preterm birth prevention.
Presentation: Friday, June 16, 2023