bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-392 Bone Mineral Density and Body Mass Index in Men with Cystic Fibrosis
Authors: Jawahar Abhinaya , Krishnasamy Sathya S , Ramirez Allan , O’Hagan Adrian , Winters Stephen J 
Published: May 2020

Abstract
Osteoporosis is an important endocrine complication of cystic fibrosis (CF). Low bone mass in CF patients has multiple contributing causes including vitamin D deficiency, calcium malabsorption, pulmonary infection and cytokine production, malnutrition, a sedentary life style, cumulative steroid dose, delayed puberty, and hypogonadism. The objective of this study was to examine the relationship between BMI and bone density of the hip and spine in adult men with CF. We conducted a retrospective chart review of adult men with CF receiving care at an academic medical center. Medical records of 43 men ages 19-60 (32.1±9.8) years were reviewed. 8 men with lung transplant, or receiving chronic glucocorticoid or androgen treatment were excluded. One subject was excluded as his BMI was &gt;3SD above the mean. BMD was measured by dual-energy x-ray absorptiometry at the lumbar spine (LS) and hip. The mean ± SD BMI of the study population was 24.10 ± 5.24 kg/m2, mean LS BMD was 0.96 ± 0.204 g/cm2 and mean hip BMD was 0.701 ± 0.382 g/cm2. Men were divided into three groups: normal BMD, osteopenia, or osteoporosis, based on current guidelines. 8 (24%) men were found to have normal bone density (Z=0.40±0.60), 19 (56%) had osteopenia (Z= -1.57±0.67) and 7 (20%) had osteoporosis (Z= -3.27±0.83). Of these 7, 6 had osteoporosis of the LS only, and one patient had osteoporosis of the hip; 5 were being treated with a bisphosphonate. The three groups of men were similar in age (P=0.93). 25OH-vitamin D levels were 22.6±4.4, 35.6±12.7 and 27.0±13.4 ng/mL, respectively (p=0.03). There was a significant (p=0.023) difference in BMI among these three groups (26.33±4.80 vs 23.25 ± 3.01 vs 20.96±3.64 kg/m2). BMI was strongly positively correlated with LS BMD (r = 0.54, P&lt;0.001) but not with BMD of the hip (r = 0.11, p=0.55). Moreover, LS BMD was highly predicted by body weight (r = 0.90, P&lt;0.0001) but not significantly by height (r = 0.26, p=0.16). These findings indicate that CF-related bone disease (CF-RBD) affecting the LS is common in adult men, and that body weight is a major determinant of LS BMD in men with CF. Possible mechanisms for this association include signaling pathways related to nutritional status and sex steroids.
OR16-04 OTX2 Mutations in Congenital Hypopituitarism Patients
Authors: Gregory Louise Cheryl , Gergics Peter , Patti Giuseppa , McCabe Mark J , Maghnie Mohamad , Spadoni Emanuela , Camper Sally A , Dattani Mehul T 
Published: May 2020

Abstract
The transcription factor OTX2 is implicated in pituitary, ocular and craniofacial development. Mutations have been described in patients with variable congenital hypopituitarism (CH) ranging from isolated growth hormone deficiency (IGHD) to combined pituitary hormone deficiency (CPHD) with/without an ectopic posterior pituitary (EPP).We aimed (i) to establish the contribution of OTX2 mutations in the etiology of CH in a sub-cohort of patients and to study their functional consequences and (ii) establish a detailed human OTX2 expression profile in a hypothalamo-pituitary (HP) context. We screened 127 patients from national (n=103) and international centers (n=24) on the septo-optic dysplasia (SOD) spectrum with variable eye abnormalities. Eye abnormalities included micro/anophthalmia, retinal dystrophy and/or coloboma in 29 of these patients, with the rest having optic nerve hypoplasia (ONH). An EPP was reported on MRI in 35 patients. The cohort previously tested negative for mutations in HESX1, SOX2, SOX3, PROKR2 and GH1. Transactivation assays involved a dual-luciferase reporter in murine hypothalamic GT1-7 neurons transiently transfected with OTX2 constructs. In situ hybridization was performed to analyze human brain OTX2 expression during embryogenesis. Seven heterozygous OTX2 changes were identified: two chromosomal deletions spanning OTX2 in patients with micro/anophthalmia, GHD and an EPP, with one patient having cerebellar hypoplasia. Three missense substitutions resulting in truncated proteins: (i) the previously reported p.S138* and (ii) p.C170*, in two patients with retinal dystrophy, EPP and IGHD respectively, and (iii) the novel p.E79* in a patient with micro/anophthalmia, EPP and CPHD. A novel insertion-deletion resulting in a truncated protein p.S167* in a patient with microphthalmia, GHD, ONH, EPP and an enlarged abnormal pituitary, and a novel deletion resulting in a frameshift p.Val139Aspfs*39 in a patient with microcephaly, microphthalmia, ONH and an EPP were also identified. The human OTX2 variants caused a significant reduction in transactivation compared to wild type. Our gene expression data identified human OTX2 transcripts in the posterior pituitary, retina, ear, thalamus, choroid plexus, and in the hypothalamus during embryogenesis, but not in RP. To conclude, we identified OTX2 variants in 7 unrelated CH patients with eye abnormalities including 3 with retinal dystrophy and one with a cerebellar abnormality. As OTX2 is involved at multiple levels during HP development, these patients should be monitored for evolving endocrinopathies. Human OTX2 is expressed in the posterior pituitary, the retina and the ear at CS19 and 20 (between 6-7 weeks gestation), and in areas of the hindbrain at CS23, but not in RP at any stage analyzed in this study. The endocrine phenotypes in patients with OTX2 mutations are most likely of hypothalamic origin.
MON-338 Severe Hypophosphatemia Induced by Intravenous Ferric Carboxymaltose Therapy for Iron Deficiency Anemia
Authors: Tam Matthew , Bhabhra Ruchi 
Published: May 2020

Abstract
Background: Ferric carboxymaltose (Injectafer), a newer intravenous iron agent permits larger iron concentrations to be delivered in fewer doses compared to traditional preparations of intravenous iron. However, ferric carboxymaltose has been shown to up-regulate fibroblast growth factor 23 (FGF23) which can result in severe hypophosphatemia. We present a case illustrating this phenomenon.
Clinical Case: A 48 year-old Caucasian female was admitted to the emergency department with complaints of gradual onset muscle weakness and severe exhaustion. Over the course of several months she noticed significant muscle weakness in all extremities.
Her co-morbidities included morbid obesity (status-post Roux-en-y bypass surgery), asthma, and hereditary angioedema. Due to her history of gastric bypass surgery, the patient required monthly iron sucrose infusions over the previous two years. Her regimen was changed to ferric carboxymaltose (Injectafer) about five months prior to the admission, receiving 750mg treatments twice monthly.
On admission, she was found to have severe hypophosphatemia of 1.5 mg/dL (2.1 – 4.7 mg/dL) with 25-OH vitamin D 21 ng/mL and PTH of 155 pg/mL. A random urinary phosphate was 72 mg/dL with a urine creatinine of 45 mg/dL, with calculated fractional excretion of phosphorus of 74%. Further diagnostic tests including EMG / nerve conduction studies, inflammatory markers, autoimmune workup, and creatine kinase were negative. She was found to have a ferritin of 2159 ng/mL (11 – 306 ng/mL) from previous baseline of 12.8 ng/mL with normal ESR and CRP. This was elucidated to be due to iron overload from IV iron infusions out of proportion to her needs. Therefore, ferrric carboxymaltose was discontinued. Her symptoms gradually improved with phosphorus and vitamin D supplementation. Two months later, when seen by Endocrinology, her ferritin was 1220 ng/mL, PTH 44 pg/mL, and phosphorus normalized to 2.6 mg/dL.
Conclusion: Ferric carboxymaltose can cause profound phosphaturia and hypophosphatemia by inhibiting the cleavage of intact FGF23 to the inactive form, a mechanism similar to autosomal dominant hypophosphatemic rickets. Previous clinical trials show the incidence of hypophosphatemia to be as high as 41-70%. We conclude that baseline phosphorus and vitamin D levels should be obtained prior to therapy and monitored closely during treatment.
Reference: Adkinson NF et al. Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial. Am J Hematol. 2018;93(5):683.
SAT-713 Novel Estrogenic Gene Regulation Induced by OTC Medications Containing Paraben Preservatives Is Dependent on Concentration that Varies Between Products and Batches
Authors: Baer Caroline , Ragland Emily , Ma Peng , Zhang Changde , Skripnikova Elena , Wiese Thomas E 
Published: May 2020

Abstract
Methylparaben, ethylparaben, and propylparaben are widely used as preservatives in food products, cosmetics, and pharmaceuticals. Parabens have been shown to be weak estrogens and this laboratory has described that extracts of some over the counter (OTC) medications with paraben preservatives can induce estrogen activity in tissue culture-based bioassays. At the same time, this laboratory determined that extracts from OTC medications containing the laxative bisacodyl induce estrogen activity regardless of parabens present and that bisacodyl is estrogenic. The current report describes the use of paraben standards and LC-MS analysis to determine paraben concentrations in extracts from OTC medications (Calcium Carbonate, Bisacodyl, Ibuprofen, Diphenhydramine, and Benzoyl Peroxide) used in previous studies. Also described is the application of the Qiagen RT2 Profiler PCR Array for Human Estrogen Receptor Signalling to determine gene induction profiles in MCF-7 cells treated with methyl, ethyl or proplyparaben, or each of the five pairs of OTC medication extracts (with or without parabens) relative to estradiol treatment. LC-MS analysis of extracts confirmed that five of six OTC medications labeled as paraben-free contain no detectable parabens, while one “paraben free” extract included measurable levels of parabens. At the same time, all of the extracts of OTC medications with paraben ingredients, some of which induce estrogen activity, were found to contain a wide range of paraben concentrations. A threshold range of paraben concentration in OTC medications is required to induce estrogen activity in bioassays. Analysis of paraben concentrations of extracts from different product lots of the same OTC medication identified discrepancies in the amount of paraben between batches. PCR Array profiles of the three paraben standards and the OTC medication extracts share some gene induction characteristics induced by estradiol. At the same time, methyl, ethyl and propylparabens induced unique gene array profiles that are shared by the OTC medication extracts containing parabens. The extracts of OTC medications containing bisacodyl stimulated a distinct gene induction profile that has some features of the profiles of estradiol and paraben treatment. This study highlights both the capacity for paraben preservatives in OTC medications to induce novel estrogen activity (gene induction) and the importance of determining the paraben concentration in OTC medications to determine estrogen potential. While the capacity for OTC medications containing parabens or other estrogenic substances to induce estrogen activity in individuals using the medications is unclear, consumers may want to know the potential for estrogen activity in these products.
SAT-418 Finding the Needles in the Haystack: Harnessing the Electronic Health Record to Find Thyroid Immune Related Adverse Events
Authors: Quandt Zoe , Trupin Laura , Evans Michael , Schmajuk Gabriela , Anderson Mark Stuart , Bluestone Jeff A , Jinoos Yazdany 
Published: May 2020

Abstract
Background: Immune checkpoint inhibitors (CPIs) are being used to effectively treat a growing number of cancers but can cause immune related adverse events (irAE). Thyroid dysfunction is the most common endocrine irAE. A meta-analysis of clinical trials estimated that following CPI exposure, 6.6% will become hypothyroid and 2.9% will have hyperthyroidism1. It is unclear if this reflects the real-world incidence of these irAEs. We used electronic health record (EHR) data to identify patients who developed thyroid dysfunction after CPI to estimate the real-world incidence of these irAEs.
Methods: Data were derived from the EHR of a large U.S. academic center. We identified subjects treated with CPIs between 2012 and 2018 and excluded those with thyroid cancer or pre-existing thyroid disease. Thyroid dysfunction was identified as either a TSH &gt; 10, an abnormal free T4 or a prescription for thyroid hormone replacement or anti-thyroid medication. Those with thyroid dysfunction were then categorized as having pre-existing disease or a new-onset thyroid irAE based on the timing of CPI initiation. Logistic regression was used to evaluate the association of thyroid irAE with age, gender, CPI and type of cancer.
Results: In total, 1146 individuals without pre-existing thyroid disease that received CPIs were assessed. Pembrolizumab was the most common treatment (45%), followed by nivolumab (20%). Less than 10% of subjects received atezolizumab, durvalumab, ipilimumab monotherapy, combined ipilimumab/nivolumab, or other combinations of CPIs. Melanoma was the most common cancer treated (32%), followed by non-small cell lung cancer (13%). The prevalence of any other cancer was &lt; 10% each. Overall, 19% developed thyroid irAEs. After adjustment for gender and age, the type of cancer was significantly associated with new onset thyroid dysfunction (p=0.01). The rates of thyroid irAEs ranged from 10% in glioblastoma to 40% in renal cell cancer. Although there was no significant association between irAEs and specific CPIs in the overall analysis, thyroid irAEs were more common in subjects who received combined ipilimumab/ nivolumab (31%) compared to pembrolizumab (18%, p=0.03), nivolumab (18%, p&lt;0.01) and ipilimumab (15%, p=0.02).
Conclusion: Thyroid irAEs are much more common in real world practice than in clinical trials and there is emerging evidence that certain cancer types incur a higher risk of thyroid irAEs even after adjustment for CPI exposure. Clinicians and patients should be educated about these risks. Future work should focus on exploring the reasons underlying the differing rates of thyroid irAEs among different cancers including effect on cancer outcomes.
1Barroso-Sousa et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens. JAMA Oncol. 2017; 02215: 1–10.
SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways
Authors: Sabatini Paul , Frikke-Schmidt Henriette , Rupp Alan , Gordian Desiree , Myers Jr Martin , Seeley Randy John 
Published: May 2020

Abstract
Growth and differentiation factor 15 (GDF15), an anorexigenic peptide that represents a promising candidate for anti-obesity treatment, acts via GDNF Family Receptor Alpha Like (GFRAL), which is expressed almost exclusively on a subset of neurons in the area postrema (AP). To determine the function and mechanisms of action for GFRAL neurons, we generated Gfralcre and conditional GfralCreERT mice. Although their chemogenetic (DREADD-mediated) activation promoted FOS in a variety of brainstem, hypothalamic, and limbic nuclei, GFRAL neurons projected only to the nucleus of the solitary tract (NTS) and the parabrachial nucleus (PBN), where they innervated and activated aversive/anorexigenic GCRP-expressing cells. Tetanus-toxin-mediated silencing of PBN CGRP neurons abrogated the aversive and anorexic effects of GDF15. Furthermore, while non-gastrointestinal (GI) stimuli (e.g., GDF15 and LPS, but not feeding or gut peptide mimetics) activated GFRAL neurons, chemogenetically activating these cells decreased gastric emptying, suppressed feeding, and promoted a conditioned taste aversion. These findings suggest that GFRAL neurons link non-GI anorexigenic signals to the control of gut physiology and to the aversive suppression of food intake. Additionally, because the chemogenetic activation of GFRAL neurons suppressed food intake more strongly than GDF15 in lean mice, additional modes of activating GFRAL neurons may augment the anorectic potential of GDF15.
OR27-05 Sexual Desire Changes in Transgender Individuals upon Initiation of Hormone Treatment; Results from the Longitudinal ENIGI Study
Authors: Defreyne Justine , Elaut Els , Kreukels Baudewijntje , Fisher Alessandra Daphne , Castellini Giovanni , Staphorsius Annemieke , Heijer Martin Den , Heylens Gunter , T’Sjoen Guy G 
Published: May 2020

Abstract
Introduction: Several steps in the transitioning process may affect sexual desire in transgender people. This is often underexposed by those providing gender affirming care. Testosterone therapy in transgender men (TM) generally leads to increasing frequency of desire, masturbation, sexual fantasies and arousal. Studies in transgender women (TW) are inconclusive: some report an increase in the prevalence of hypoactive sexual desire after initiation of hormone therapy, whereas others have shown a positive impact of hormonal therapy on sexual quality of life. The current study prospectively assesses sexual desire during the first three years of hormonal therapy (HT) in transgender people. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Sexual desire was prospectively assessed in 766 participants (401 TW, 364 TM) by Sexual Desire Inventory (SDI) during a three-year follow-up period, starting at the initiation of hormone treatment (HT). SDI scores were analyzed as total, dyadic and solitary SDI scores. At baseline, psychological questionnaires were administered. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectionally and prospectively. Results: In TW, total, dyadic and solitary SDI scores decreased during the first three months of HT. However, after 36 months, total and dyadic SDI scores were higher than baseline scores. Solitary scores after 36 months were comparable to baseline scores. In TM, total, dyadic and solitary SDI scores increased over the first three months, remaining stable thereafter. However, total and dyadic SDI scores after thirty-six months were comparable to baseline scores, whereas solitary scores remained higher than baseline. Factors associated with a prospective increase in SDI scores included having undergone gonadectomy, no longer experiencing vaginal bleedings (in TM) or higher gender dysphoria levels at baseline (in TM only). Factors associated with higher cross-sectional SDI scores included being in a relationship, undergoing gonadectomy, no longer experiencing vaginal bleedings (TM), lower gender dysphoria scores (TW only) and lower body dysphoria scores (TW only). Conclusion: Gender affirming hormonal therapy induces short-term changes in sexual desire in transgender people. Over a longer period of time, a net increase in dyadic sexual desire in TW receiving feminizing HT was observed. Sexual desire scores comparable to baseline in TM receiving virilizing HT were found. We observed no correlation between sexual desire and absolute serum testosterone levels. However, other factors, including undergoing gonadectomy, persistence of vaginal bleedings (in TM) and psychological factors may influence sexual desire in transgender people.
SAT-301 Relationship Between Clinicopathological Aspects and MSH6/MSH2 and PD-L1 Expressions in Clinically Nonfunctioning Pituitary Adenomas
Authors: Uraki Shinsuke , Ariyasu Hiroyuki , Doi Asako , Takeshima Ken , Morita Shuhei , Fukuhara Noriaki , Inoshita Naoko , Nishioka Hiroshi , Nakao Naoyuki , Yamada Shozo , Akamizu Takashi 
Published: May 2020

Abstract
Introduction: Mismatch repair (MMR) genes are associated with the MMR mechanism that corrects DNA polymerase misincorporation errors. We analyzed the aggressive pituitary adenomas (PAs) associated with Lynch syndrome due to germline mutation in the MMR gene. Reduced expression of MMR genes mutS homologs 6/2 (MSH6/2) directly promotes PA growth (1, 2). MMR gene expression and programmed cell death 1 ligand 1 (PD-L1) expression are involved in tumor immunity with immune checkpoint inhibitors, but the direct association in PAs is not fully understood. Hypothesis and Objectives: MSH6/2 and PD-L1 expression could affect PA proliferation and invasion by pathological classification of nonfunctioning (NF) PAs because the proliferation and invasiveness differ depending on the PA histological subtype. In this study, we therefore analyzed the correlation between MSH6/2 and PD-L1 mRNA expression levels and clinicopathological factors related to tumor proliferation using human NFPAs. Experimental Design: We performed immunohistochemistry to classify the NFPAs into gonadotroph adenomas (GAs), silent corticotroph adenomas (SCAs), null cell adenomas (NCAs) and pituitary transcription factor 1 (PIT1) lineage PAs according to 2017 WHO classifications. Quantitative analyses were by real-time PCR to detect MSH6/2 and PD-L1 mRNA expressions in NFPAs (n = 89). We also performed statistical analyses of the expressions and clinicopathological factors such as Knosp Grade and histological subtypes. We investigated the effect of MSH6 knockout on cell proliferation and PD-L1 expression in AtT-20ins cells. Major Results: MSH6/2 expression was positively associated with PD-L1 expression. MSH6/2 and PD-L1 expressions are significantly lower in invasive NFPAs with Knosp Grade 3–4 or recurrence than in non-invasive NFPAs with Knosp Grade 1–2. Their expression is significantly lower in SCAs and NCAs than in GAs. Although MSH6/2 expression also tends to be lower, the PD-L1 expression tends to be higher in PIT1 lineage PAs, which is unlike SCAs and NCAs. MSH6 knockout in AtT-20ins significantly decreased PD-L1 expression with cell proliferation promotion. Interpretation of results and Conclusion: MSH6/2 and PD-L1 expressions of SCAs, NCAs, and PIT1 lineage PAs compared to GAs were thought to contribute to their clinically aggressive behaviors. The molecular mechanism of the difference in clinical features of NFPAs was partially elucidated. In particular, reduced expressions of MSH6/2 were thought to be useful for predicting the proliferation and invasiveness of NFPAs.
References: (1) Uraki S et al., Endocr J. 2017;64(9):895–906 (2) Uraki S et al., J Clin Endocrinol Metab. 2018;103(3):1171–1179. Declarations of conflicts of Interest: No authors declare any conflicts of interest.