bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-373 Addressing the Burden of Hip Fracture in Older Men
Authors: Khan Mehreen , Hamann Kendal , Chandra Malini , Hui Rita , Fulchino Lisa , Lo Joan Chia-Mei 
Published: May 2020

Abstract
INTRODUCTION: Men have a lower incidence of hip fracture compared to women. However, hip fractures comprise a greater proportion of overall fractures in men and result in greater morbidity and mortality. In 2015, a new high-risk fracture prevention program was implemented in our medical group, targeting men aged 70-85y with hip, pelvic, humerus, wrist or vertebral fracture for osteoporosis treatment within 6 months of the fracture event. In this study, we examined patient characteristics, site of hip fracture, treatment initiation and time to treatment initiation in men who experienced a hip fracture before and after implementation of this new fracture prevention program.
METHODS: This study examines data from 1114 men age 70-85y (81% white race) who experienced a hip fracture during 2013-2014 (N=527) and 2015-2016 (N = 587), based on a principal hospital discharge diagnosis, excluding men who had received osteoporosis treatment in the prior year. Initiation of osteoporosis treatment within 6 months following the hip fracture and time to initiation of osteoporosis treatment (bisphosphonate, teriparatide, denosumab) were examined. The following covariates were ascertained using data from electronic health records and databases: age, race/ethnicity, smoking status, body mass index (BMI), and history of diabetes mellitus with diabetes pharmacotherapy. A Charlson Comorbidity Index was derived using health record data form the prior year. The site of hip fracture was classified as femoral neck or pertrochanter. Subgroups were compared using the Chi-square test.
RESULTS: Among the 1114 men with hip fracture (mean age 79 ± 4 years), half (54%) experienced a fracture in the femoral neck and the remainder (46%) in the pertrochanter. Nearly 1 in 5 (17%) men were current smokers, 13% were obese (BMI ≥30 kg/m2), 25% had diabetes mellitus, and 42% had a comorbidity index ≥3. One fourth (24%) had a clinical fracture diagnosed in the past 2 years. Osteoporosis treatment initiation post-hip fracture increased from 16% in 2013-2014 to 29% in 2015-2016 with implementation of the high-risk program targeting men (p&lt;0.01). Time to treatment examination of 2013-2014 vs 2015-2016 revealed that the largest increase in treatment initiation was seen at 2-4 months (4% vs 12%, p&lt;0.01) whereas non-significant differences were seen at ≤2 (7% vs 10%) and 4-6 (4% vs 7%) months following hip fracture.
CONCLUSION: Implementing targeted post-hip fracture intervention in men dramatically increased osteoporosis treatment following fracture, with the largest intervention seen 2-4 months after fracture. The high burden of prevalent fractures, smoking, and diabetes highlights the need for post-fracture intervention and counseling for modifiable risk factors.
SUN-270 The Exploding Pituitary - A Case of Atypical Meningitis
Authors: Alhaque Abid , Deininger Kelly , Zabad Manal , Horani Mohamad Hosam 
Published: May 2020

Abstract
Introduction : Pituitary apoplexy is a rare presenting pathology of a pituitary mass. Apoplexy means “sudden attack”, which is a fitting description of the patient’s presentation. Apoplexy is breakdown of the pituitary gland due to insufficient blood flow, leading to ischemia, necrosis, and hemorrhage. Two proposed mechanisms exist: 1. Supra-sellar masses can outgrow their blood supply, 2. Growth inside the suprasellar fossa can constrict blood flow. Patients with pituitary apoplexy typically present with abrupt onset of severe headache, nausea, vomiting, altered level of consciousness, visual impairment and endocrine deficiency. Sheehan took credit for obstetric associated pituitary necrosis however, apoplexy can also be life threatening outside of pregnancy.
Case Presentation : This case features 68-year-old females w history of migraines, bradycardia requiring a pace maker, CAD s/p stents, Rheumatoid Arthritis, and urothelial carcinoma of the left kidney which resulted in unilateral nephrectomy. Following surgery: Patient developed generalized weakness, weight loss, Headache. Presented later to ED with severe headache, photophobia, and hypotension. CT Head showed growth of suprasellar mass, edema of hypothalamus and thalamus. Laboratory tests showed Free T4 0.39 (08-1.7), LH &lt; 0.3, FSH 3.7, Ptolactin diluted 85.7, Low Utine Osm 105, cortisol baseline 6.9, cortisol 60 min value post high dose Cosytropin stimulation was 15.5.Spinal fluid analysis was suggestive of aseptic meningitis. Our patient was treated for 10 days in ICU for Sepsis syndrome and viral meningitis before Endocrine consult was obtained, then he got started on hormonal treatment and referred to pituitary Neurosurgeon. Patient underwent Transphenoidal surgery. Pathology revealed Metastasis of Urothelial cancer to pituitary.
DISCUSSION & CONCLUSION: Apoplexy causing an atypical meningitis is a rare presentation. We theorize apoplexy can lead to aseptic meningitis by leakage of blood or necrotic tissue into the subarachnoid space. Either agent can induce a cytokine mediated response and the presentation of meningitis. Based on CTs, our patient’s pituitary tumor grew significantly in 30 days. Medical management of pituitary apoplexy includes fluid electrolyte balance, glucocorticoids, hemodynamic monitoring, replacement of missing hormones, and the use of Decadron to decreases cerebral edema. Diabetes insipidus was an alarming symptom for possible metastatic cancer to pitutary
CONCLUSION
This case highlights the difficulty in diagnosing pituitary pathologies and the rare presentation of apoplexy. Aseptic meningitis and a decrease in centrally controlled hormones should alert Physicians to include pituitary apoplexy in the differential diagnosis. Metastatic urothelial cancer to pituitary is extraordinarily uncommon.
MON-723 Identification of Thyrotrope Signature Genes and Regulatory Elements
Authors: Daly Alexandre , Cheung Leonard , Brinkmeier Michelle , Camper Sally Ann 
Published: May 2020

Abstract
Recent genome wide association studies have begun to identify loci that are risk factors for sporadic pituitary adenomas, but the genes associated with these loci are unknown. In general, ~90% of GWAS hits are in noncoding regions, making it difficult to transition from genetic mapping to a biological understanding of risk factors. Recent studies that identify enhancer regions by undertaking large scale functional genomic annotation of non-coding elements like Encyclopedia of DNA Elements (ENCODE) have begun to yield a better understanding of some complex diseases. Dense molecular profiling maps of the transcriptome and epigenome have been generated for more than 250 cell lines and 150 tissues, but pituitary cell lines or tissues were not included. Epigenetic and gene expression data are emerging for somatotropes, gonadotropes and corticotropes, but there is very little available data on thyrotropes. We identified the transcription factors and epigenetic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an early, undifferentiated Pou1f1 lineage progenitor (GHF-T1) and a committed thyrotrope (TαT1). TαT1 is an excellent cell line for this purpose because it responds to TRH, retinoids, and secretes TSH in response to diurnal cues. We have also used genetic labeling and fluorescence activated cell sorting to purify thyrotropes from pituitaries of young mice and analyzed gene expression using single cell transcriptomics. We used the Assay for TransposaseAccessible Chromatin with sequencing (ATACseq) and Cleavage Under Target and Release Using Nuclease (CUT&RUN) to identify POU1F1 binding sites and histone marks associated with active enhancers, H3K27Ac and H3K4Me1, or inactive regions, H3K27Me3, in GHF-T1 and TαT1 cells. We integrated DNA accessibility, histone modification patterns, transcription factor binding and RNA expression data to identify regulatory elements and candidate transcriptional regulators. We identified POU1F1 binding sites that were unique to each cell line. For example, POU1F1 binds sites in and around Cga and Tshb only in TαT1 cells and Twist1 and Gli3 only in GHFT1 cells. POU1F1 binding sites are commonly associated with bZIP factor consensus binding sites in GHFT1 cells and Helix-Turn-Helix or basic Helix-Loop-Helix in TαT1 cells, suggesting classes of transcription factors that may recruit POU1F1 to unique sites. We validated enhancer function of novel elements we mapped near Tshb, Gata2, and Pitx1 by transfection in TαT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice. These data extend the ENCODE analysis to an organ that is critical for growth and metabolism. This information could be valuable for understanding pituitary development and disease pathogenesis.
SAT-247 Use of Double Dopamine Agonists in Giant Prolactinomas: A Series of 6 Cases
Authors: Kuan Yueh Chien 
Published: May 2020

Abstract
Dopamine agonist monotherapy is first line therapy in giant prolactinomas even when visual field defect is present. The costlier cabergoline is often preferred over bromocriptine due to higher efficacy and tolerability profile. Described herein combined cabergoline and bromocriptine therapy in 6 cases of giant prolactinomas. Retrospective records review of 6 patients with giant prolactinoma (3 males: M1-M3, 3 females: F1-F3) in a single tertiary centre was performed. Mean age at diagnosis: 29 years (range 17-39). Mean duration of follow up: 7 years (range 3-11). Headache and visual field defect were the presenting symptoms in all cases. Basal prolactin concentration: 100000 to 468851 mIU/L (&lt;300 for male, &lt;600 for female). Three patients have hypopituitarism at presentation, one after surgery and one remained eupitary 5 years after diagnosis. One developed late onset hypopituitarism 4 years after normalisation of prolactin levels. Three patients underwent debulking at presentation because of significant mass effects with obstructive hydrocephalus. In all patients cabergoline 1-1.5 mg/wk was started at diagnosis and gradually increased to 0.5 mg daily, aiming for normoprolactinemia. From May 2017 bromocriptine were given to these patients who continued to have hyperprolactinemia despite cabergoline 3.5-4mg/wk. Bromocriptine was commenced 1.25-5mg/day and gradually increased to 10 mg/day on top of cabergoline with careful monitoring of prolactin levels and side effects. Cabergoline was tapered down to 1.5-2mg/wk if prolactin levels remained stable between 2-3x normal while maintaining dose of bromocriptine. In M1, cabergoline was tapered off while maintaining bromocriptine 10mg/day with stable prolactin levels (~1000 mIU/L). In M2, normoprolactinemia was achieved after adding on bromocriptine and is currently on cabergoline 2mg/week and bromocriptine 10mg/day. In M3, whose prolactin were 4x normal value despite cabergoline 3.5mg/week, decreased 50% with bromocriptine 5 mg/day and remained stable when cabergoline reduced to 1.5mg/week. F1 had transphenoidal section twice due to failure of medical therapy. Her prolactin remained markedly elevated 10000-20000 mIU/L despite cabergoline 3.5 mg/week and bromocriptine 10mg/day, with persistent bitemporal hemianopia. F2 developed erythema nodosum after starting bromocriptine which was stopped and continued with cabergoline 1 mg/week. F3 showed partial response with 50% reduction in prolactin to 4485 mIU/L with bromocriptine 10 mg/day and cabergoline 1.5mg/week. In patients who underwent debulking, residual tumour remained unchanged. Two patients - tumour shrank 40% (F2) and 90% (M3) with medical therapy alone. In conclusion, adding on bromocriptine can be considered when high dose cabergoline is required for treatment of giant prolactinoma with careful monitoring. This reduces cabergoline dose which saves cost.
MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism
Authors: wang wei 
Published: May 2020

Abstract
Primary aldosteronism (PA) is the most common cause of secondary hypertension. Overseas flow surveys show that compared with essential hypertension (EH), the risk of cardiovascular and cerebrovascular diseases and kidney damages in PA patients is increased, and the mortality rate of cardiovascular events is higher than that in EH patients, in addition,this effect is independent of elevated blood pressure. The difference of cardiac damage between PA and EH patients was analyzed by echocardiography. Methods From April 28, 2017 to April 28, 2019, patients with primary aldosteronism diagnosed by ICD in Department of Endocrinology and Metabolism, Department of Cardiology and Urology were extracted from the adrenal group database of the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, and ICD diagnosis in Department of Endocrinology and Metabolism during the same period was also extracted. In patients with essential hypertension, the differences of clinical indicators and echocardiography between the two groups were compared, and the differences of cardiac damage and related risk factors between the two groups were explored. Results 295 patients were included in this study, including 148 patients in PA group (50.17%) and 147 patients in EH group (49.83%). There was no significant difference in gender, age, BMI, course of disease and average blood pressure between the two groups (P &gt; 0.05). The levels of serum aldosterone and BNP in PA group were significantly higher than those in EH group, and the levels of serum renin and minimum blood potassium were significantly lower than those in EH group (P &lt; 0.05). Left ventricular diameter (LV), left atrial diameter (LA), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), ascending aorta diameter (AAO), end-diastolic diameter (EDD), end-diastolic volume (EDV) and stroke volume (SV) in PA group were significantly higher than those in EH group (P &lt; 0.05). It was significantly higher than that in EH group (P &lt; 0.05). The correlation analysis of variables with statistical significance between the two groups showed that serum renin activity level was negatively correlated with LV, AAO, EDD and SV, and the lowest serum potassium level was negatively correlated with LVPW and AAO. CONCLUSION Compared with EH of the same age, course of disease and blood pressure level, PA patients are more likely to suffer from cardiac damage, which is manifested by heart growth, ventricular septal thickening and cardiac function decline, and is closely related to the inhibition of serum renin activity and serum potassium level. Clinical attention should be paid to early screening and treatment of PA and its complications in order to reduce the risk of cardiac death.Key words: primary aldosteronism; echocardiography; cardiovascular risk factors
MON-714 CRISPR / Cas9 Genomic Edition of the CDH2 Gene in Zebrafish Leads to Eye and Cardiac Malformation
Authors: Ventura Bianca Helena , Bissegatto Débora Delmonte , Arnhold Ivo J , Carvalho Luciani Renata Silveira 
Published: May 2020

Abstract
Introduction: The CDH2 gene encodes a transmembrane protein responsible for calcium-dependent cell-cell adhesion that participates in the process of embrionic development. Neural development is achieved by neuronal neurulation, migration and differentiation, as well as axon growth and synapse formation. During pituitary development, CDH2 was associated to the epithelium-to-mesenchymal transition, with cell migration from the marginal zone to the anterior pituitary gland, followed by terminal differentiation. Thus, a dysfunction in n-cadherins disrupts the architecture of the neural tube, cortical architecture of the embryonic brain and pituitary development. In a previous study in our laboratory, a patient was diagnosed with a homozygous variant located in the N-terminal region of CDH2 (p.Val289IIe) that culminated in congenital hypopituitarism and pituitary hypoplasia. Together, these observations indicate that cadherins, especially N-cadherin, play an indispensable role in the organization of neuroepithelial layers. Zebrafish has been widely used as a model for studies of gene functionality, as it has 70% genetic homology to humans, besides being a small animal with rapid development. Our goal was to generate a zebrafish knockout for the CDH2 gene, using CRISPR Cas9 genomic edition to study its importance during development and analyze this gene in patients with characteristics similar to those observed in zebrafish. Material and methods: Three guides were drawn for the CDH2 gene using crispor program. sgRNA, produced by in vitro transcription, and Cas9 protein were injected into one cell stage. All developmental parameters were observed under a microscope up to 96 hours post fertilization (hpf). Mortality rate were calculated at 24, 48, 72 and 96 hpf. The embryos were genotyped to confirm the deleterious allelic variant. CDH2 coding region was evaluated in 3 female siblings, born from consanguineous parents, presenting micro/anophtalmia and short stature. Exons 2 to 16 were sequenced by the Sanger method. Results: 352 eggs were injected and several deformities such as absence of somites, cardiac edema, spinal curvature, cranial malformation and microphthalmia or total absence of eyes were observed. The mortality rates were 26%, 31%, 40% and 62% at 24, 48, 72 and 96 hpf, respectively. The Sanger sequencing from DNA extracted from the whole animal presented deleterious effect classified as insertions, deletions and missense changes. No deleterious allelic variant was observed in the 15 analyzed exons in the 3 patients. Conclusion: The CDH2 gene is important for neurodevelopment and eyes formation in the zebrafish although pathogenic allelic variants in this gene was not found in the studied patients with short stature and eye abnormalities.
SUN-348 Growth Hormone Replacement in Adults During 8 Years Leads to Sustained Increase in Bone Mineral Density
Authors: Payer Juraj , Kužma Martin , Stojkovičová Daša , Smaha Juraj , Jackuliak Peter , Killinger Zdenko 
Published: May 2020

Abstract
Introduction: Adult growth hormone deficiency (AGHD) is associated with lower bone mass and likely with increased risk of fragility fractures. GH replacement leads to increase in bone mineral density (BMD).However, only few studies longer than 2 years exist. Aim: To assess long-term effect of recombinant GH replacement on BMD and bone turnover markers duringperiod of 8 years. Patients & Methods: Prospective follow-up of all (N=63) AGHD patients at one single center. All patients with adult GHD followed at single center. All participants were replaced with daily injection of recombinant human (rh) GH in IGF-1 normalizing regimen according to Endocrine Society Guidelines. Every 2 years, lumbar spine (L-spine) and total hip (TH) BMD using dual X-ray absorptiometry on Hologic Discovery device, was assessed. All patients were assessed for bone turnover markers; carboxy-terminal collagen crosslinks (CTx) and osteocalcin (OC), and 25(OH)D levels. Deficiencies of other pituitary axes were treated if necessary. All patients were supplemented with 800 IU /day of cholecalciferol and 1000-1200mg/day of calcium as recommended by International Osteoporosis Foundation. Results: Study group consisted of 38 males and 25 females (35 with adult onset (AO) /28 with childhood onset (CO); mean age at diagnosis 25,1 yrs) AGHD patients. All patients ended 8 years follow-up period without any treatment discontinuation during this period. Treatment was well tolerated, without any serious adverse event. IGF-1 has reached the normal ranges during first 6 months and remains normal during whole study period documenting good adherence to treatment (average dose of rhGH=0,4 mg/day). Both, L-spine and TH BMD increased significantly after 8 years of GH replacement (+8 % for L-spine BMD, +7,7% for TH BMD, both p&lt;0,01). The highest peak of BMD was observed after 6 years of treatment. CTx increased by 35% (p&lt;0,05) and remain stable, and no significant change in OC was observed during study period. Levels of 25(OH)D increased by 32% (p&lt;0,05) from baseline. No clinical fractures were observed. Conclusion: Long-term GH replacement in adult GHD together with sufficient levels of vitamin D levels led to increase in BMD and CTx. This study supported fact that GH has sustained effect on bone mass and bone turnover and is safe and well -tolerated for the long time period.
SAT-309 Integrated Analysis of Pituitary Adenoma Using Novel Approach of Non-Target Proteomics Along with RNA-Sequencing Analyses
Authors: Gao Yue , Nagano Hidekazu , Horiguchi Kentaro , Hashimoto Naoko , Nakayama Akitoshi , Higuchi Seiichiro , Yamagata Kazuyuki , Yokoyama Masataka , Iwadate Yasuo , Tanaka Tomoaki 
Published: May 2020

Abstract
Objective: To clarify the relationship between proteomic expression and clinical feature of pituitary adenoma. Methods: We have previously developed non-target proteomics analysis, which enables to detect and quantify approximately 7,000 to 9,000 kinds of protein weave, in parallel with RNA-seq analysis, and then subjected to 14 cases of pituitary adenoma surgically removed at Chiba University Hospital. Bioinformatic evaluation including DEGs, heatmap and PCA analyses was performed to reveal underlying their molecular pathogenesis. Results: We successfully identified 789 differentially expressed proteins and 593 DEGs in non-target proteomics and RNA-seq, respectively. Intriguingly, PCA analysis demonstrated that tumors were clearly divided into 3 groups based on protein expression profile; functional pituitary adenomas consisting of two subtypes depending on Pit1 and T-pit linage, and non-functional tumors consisting of two distinct subtypes, with properties close to functional tumors and unique characteristics of hard tumor difficult to remove by endoscopic surgery. To address the underlying molecular biological functions in each group clustering analysis and heat-map were performed and we found that 3 groups were separated clearly with their own both gene and protein expression profile. Indeed, for instance, GO term of plasma membrane part was significantly enriched in hard tumor group, pathways of GH receptor signaling, GH hormone synthesis as in GH-positive group. Conclusions: We herein demonstrate that pituitary adenoma can be uniquely separated into certain categories through our novel non-target proteomics with coupling to RNA-seq, particularly providing novel group of hard tumor characteristics with enriched expression of both protein and mRNA in plasma membrane part. Thus our method would be beneficial and useful to elucidate underlying molecular pathogenesis for pituitary tumors, while further analysis is required.