bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-934 A Rare Case of Hyperparathyroidism - Parathyroid Carcinoma, Atypical Adenoma, or Both?
Authors: Krutilova Petra , Sandhu Harjyot , Salim Michael , Gilden Janice L , Butler Paula 
Published: May 2020

Abstract
Introduction: Parathyroid carcinoma (PC) is a rare endocrine malignancy. It accounts for &lt;1% cases of primary hyperparathyroidism (PHPT). We present a rare case of concurrent PC and atypical parathyroid adenoma (PA).
Case presentation: A 72-year-old woman presented with 1-week history of generalized weakness, confusion, and auditory hallucinations. Her medical history was significant for PHPT known for 5 years, CAD and CHF. The patient appeared mildly volume depleted and was tachycardic (105/min). The rest of her physical exam was unremarkable. Calcium (Ca) was 15.1 mg/dL (8.4–10.2 mg/dL) and intact PTH 451.9 pg/mL (12–88 pg/mL). Her condition improved with aggressive fluid replacement, pamidronate, and cinacalcet. A sestamibi scan revealed increased uptake of bilateral parathyroid tissue. Fine needle aspiration (FNA) revealed PA. Surgical treatment was postponed for control of cardiac comorbidities. One month later, she presented again with symptomatic hypercalcemia. Her Ca was 16.1 md/dL and PTH 761.5 pg/mL. Initial medical management was followed by subtotal parathyroidectomy – three masses were removed (one on the right and two on the left). Final pathology revealed PC within the left parathyroid, the others were consistent with hypercellular parathyroid tissue. One month later, the patient underwent left hemithyroidectomy, right parathyroidectomy, and central neck dissection. PTH level dropped to 2.4 pg/mL and Ca level was 7.6 mg/dL after surgery. She was discharged home on Ca and vitamin D supplements. Pathology was sent to a referral cancer center and revealed PC vs. atypical PA within the right parathyroid.
Discussion: PC is a rare endocrine malignancy. Further, there are not many cases of synchronous PC and PA or multifocal PC. Diagnosing PC preoperatively is challenging since it shares overlapping characteristics with PA. Patients with malignancy commonly present with larger tumor size, higher level of Ca (&gt;14.6 mg/dL), and PTH (5-fold higher than the upper limit of normal). Our patient had a history of multiple admissions due to symptomatic HC. She had no palpable neck masses on exam. Her initial FNA was consistent with PA. Hence, we presumed that her hypercalcemia was caused by PA. Establishing a definitive diagnosis of PC by frozen sections intraoperatively is difficult. Histopathologic findings of atypical cells, high mitotic rate, and cellular invasions can suggest the diagnosis, though they are often negative. Even postoperatively, pathologists often disagree on cytologic interpretation. However, differentiating PA and PC is important since earlier and more aggressive treatment is needed to reduce the morbidity and mortality in case of malignancy.
SAT-637 Patient-Centered Glycemic Management of Type 2 Diabetes with Mobile Applications
Authors: Lau Chap-Kay K , Wu Gloria , Leung Brian , Momen Donia , Luu Shannon 
Published: May 2020

Abstract
BACKGROUND: Ehealth apps have 3.7 billion downloads yearly. The accessibility of diabetes mobile applications allows for patient self-management of diabetes. Renal and cardiovascular complications,1 which play a role in diabetic patient outcomes, are newly highlighted by the 2019 American Diabetes Association’s Standards of Medical Care in Diabetes.2
Purpose: To evaluate free Android mobile apps using the Diabetes Self-Management Education and Support (DSMES) and the 2019 American Diabetes Association (ADA) guidelines for renal and cardiovascular complications.
Methods: Using the search term “diabetes,” Google Play store was accessed. Inclusion criteria: 1) Apps with downloads 1M-100,000; 2) free; 3) DSMES criteria; and 4) medication adherence. Exclusion criteria: 1) Purely educational factual apps on diabetes; 2) no ranking or download information. Google displayed a list of 10 free apps in 2019. The 2019 apps were analyzed for DSMES criteria, renal and cardiovascular complications (ADA 2019), and medication adherence via push notification.
Results: The top 10 mobile apps in descending order were: 1) mySugr, 2) Onetouch Reveal, 3) OneDrop Diabetes Management, 4) Diabetes: M, 5) Diabetes, 6) Ontrack Diabetes, 7) Health2Sync, 8) Diabetes Connect, 9) Glucose Buddy Diabetes Tracker, 10) Blood Glucose Tracker. All of the mobile apps had the functionality of tracking blood glucose levels. 8/10 had the ability of tracking HbA1C levels. The percent of DSMES incorporation within the apps ranged from 18.2%-81.8%. None of the apps used all the DSMES guidelines or 2019 ADA. Only 1/10 of the mobile apps had the ability to track the presence of heart palpitation and retina/eye issues recommendations. None of the apps had the ability to track cardiovascular and renal complications. 7/10 of the apps had medication reminders (sound notification) and 4/10 of the apps had push notifications.
Conclusion: eHealth mobile apps could be a powerful tool for patient self-management of diabetes. Currently, none of the apps incorporate all of the DSMES or ADA guidelines regarding comorbidities and complications of diabetes. Despite these shortcomings, these apps provide an introduction to the concept of patient-centered tracking of health data. We look for future improvements as more physicians use the apps and provide feedback to the app developers and eHealth commerce space.
References
1.
Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701
2.
American Diabetes Association. 4. Comprehensive medical evaluation and assessment of comorbidities: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019;42(Suppl. 1):S34-S45
SAT-547 Aldosterone-Potassium Ratio Predicts Primary Aldosteronism Subtype
Authors: Puar Troy , Loh Wann Jia , Lim Dawn Shao Ting , Zhang Meifen , Foo Roger S , Lee Lynette , Khoo Joan J C , Tay Donovan , Dekkers Tanja , Velema Marieke Stientje , Deinum Jaap , Kek Peng Chin 
Published: May 2020

Abstract
Objective Prediction models have been developed to predict either unilateral or bilateral primary aldosteronism, and these have not been validated externally. We aimed to develop a simplified score to predict both subtypes and validate this externally.
Methods Our development cohort was taken from 165 patients who underwent adrenal vein sampling (AVS) in two Asian tertiary centres. Unilateral disease was determined using both AVS and post-operative outcome. Multivariable analysis was used to construct prediction models. We validated our tool in a European cohort of 97 patients enrolled in a clinical trial. Previously published prediction models were also tested in our cohorts.
Results Backward stepwise logistic regression analysis yielded a final tool using baseline-aldosterone-to-lowest-potassium ratio (APR, ng/dL/mmol/L), with an area under receiver operating characteristic curve of 0.80 (95% CI: 0.70 - 0.89). In the Asian development cohort, probability of bilateral disease was 90.0% (with APR &lt;5) and probability of unilateral disease was 91.4% (with APR &gt;15). Similar results were seen in the European validation cohort. Combining both cohorts, probability of bilateral disease was 76.7% (with APR &lt;5), and probability for unilateral was 91.7% (with APR &gt;15). Other models had similar predictive ability but required more variables, and were less sensitive for identifying bilateral PA.
Conclusion The novel aldosterone-potassium ratio (APR) is a convenient score to guide clinicians and patients of various ethnicities on the probability of PA subtype. Using APR to identify patients more likely to benefit from AVS may be a cost-effective strategy to manage this common condition.
SAT-298 Integrative Single-Cell Transcriptomic and Epigenomic Landscape of Mouse Anterior Pituitary Cell Types
Authors: Ruf-Zamojski Frederique Murielle , Zamojski Michel A , Nudelman German , Ge Yongchao , Mendelev Natalia , Smith Gregory R , Zhou Xiang , Toufaily Chirine , Schang Gauthier , Gambino Luisina Ongaro , Liu Hanqing , Gomez Castanon Rosa G , Moriwaki Mika , Nair Venugopalan , Pincas Hanna , Nery Joseph R , Bartlett Anna , Alridge Andrew , Odle Angela Katherine , Childs Gwen V , Turgeon Judith L , Welt Corrine Kolka , Ecker Joseph R , Bernard Daniel J , Sealfon Stuart C 
Published: May 2020

Abstract
The pituitary gland is a critical regulator of the neuroendocrine system. To further our understanding of the classification, cellular heterogeneity, and regulatory landscape of pituitary cell types, we performed and computationally integrated single cell (SC)/single nucleus (SN) resolution experiments capturing RNA expression, chromatin accessibility, and DNA methylation state from mouse dissociated whole pituitaries. Both SC and SN transcriptome analysis and promoter accessibility identified the five classical hormone-producing cell types (somatotropes, gonadotropes (GT), lactotropes, thyrotropes, and corticotropes). GT cells distinctively expressed transcripts for Cga, Fshb, Lhb, Nr5a1, and Gnrhr in SC RNA-seq and SN RNA-seq. This was matched in SN ATAC-seq with GTs specifically showing open chromatin at the promoter regions for the same genes. Similarly, the other classically defined anterior pituitary cells displayed transcript expression and chromatin accessibility patterns characteristic of their own cell type. This integrated analysis identified additional cell-types, such as a stem cell cluster expressing transcripts for Sox2, Sox9, Mia, and Rbpms, and a broadly accessible chromatin state. In addition, we performed bulk ATAC-seq in the LβT2b gonadotrope-like cell line. While the FSHB promoter region was closed in the cell line, we identified a region upstream of Fshb that became accessible by the synergistic actions of GnRH and activin A, and that corresponded to a conserved region identified by a polycystic ovary syndrome (PCOS) single nucleotide polymorphism (SNP). Although this locus appears closed in deep sequencing bulk ATAC-seq of dissociated mouse pituitary cells, SN ATAC-seq of the same preparation showed that this site was specifically open in mouse GT, but closed in 14 other pituitary cell type clusters. This discrepancy highlighted the detection limit of a bulk ATAC-seq experiment in a subpopulation, as GT represented ~5% of this dissociated anterior pituitary sample. These results identified this locus as a candidate for explaining the dual dependence of Fshb expression on GnRH and activin/TGFβ signaling, and potential new evidence for upstream regulation of Fshb. The pituitary epigenetic landscape provides a resource for improved cell type identification and for the investigation of the regulatory mechanisms driving cell-to-cell heterogeneity.
Additional authors not listed due to abstract submission restrictions: N. Seenarine, M. Amper, N. Jain (ISMMS).
SAT-562 Angiotensin II Induces Aldosterone Synthesis in the Rat Heart Stressed by Angiotensin II
Authors: Bose Himangshu S , Whittal Randy M , Rajapaksha Maheshinie , Marshall Brendan , Wang Ning-Ping , Perry Elizabeth W , Zhao Zhi-qing , Miller Walter L 
Published: May 2020

Abstract
Aldosterone (Aldo) causes myocardial injury and fibrosis. While most Aldo is made by the adrenal zona glomerulosa; there have been controversial reports that Aldo is also synthesized in the heart; such myocardial synthesis of Aldo might contribute to myocardial injury. We induced cardiac fibrosis in rats by infusing angiotensin II (AngII) @ 500 ng/kg/min via subcutaneous pumps. After 4 weeks, circulating corticosterone increased about 400-fold from ~29 nM to ~11 μM. Aldo synthesis in isolated mitochondria (mito) was assessed by conversion of tritiated deoxycorticosterone to Aldo; AngII infusion doubled Aldo synthesis, and this augmented synthesis was inhibited in mito from rats receiving AngII + telmisartan, which inhibits the binding of AngII to the AT1 receptor. Western blotting showed P450c11AS (Aldo synthase) was also stimulated by AngII and inhibited by telmisartan in both rat heart and H9c2 myocardial cells. 2-dimentional native PAGE and mass spectrometry showed that a 290-kDa complex on the inner mitochondrial membrane (IMM) contained P450c11AS, Tom22 (a translocase associated with the outer mitochondrial membrane, OMM), and StAR (the steroidogenic acute regulatory protein). Immunocytochemistry and transmission electron microscopy monitoring of immune-gold particles confirmed that P450c11AS, Tom22, and StAR were associated with the mito, that P450c11AS and StAR were associated with the IMM and that P450c11AS and StAR, but not Tom22, were increased by AngII. Cardiac Aldo synthesis required myocardial expression of P450c11AS, but expression of P450scc, the initial steroidogenic enzyme that converts cholesterol to pregnenolone, was undetectable, indicating the heart cannot make Aldo de novo from cholesterol. The only known action of StAR is to promote the movement of cholesterol from the OMM to IMM; nevertheless, we found that intramitochondrial StAR is required for Aldo synthesis; protein crosslinking with BS3 showed that Tom22 forms a bridge between StAR and P450c11AS. This is the first activity ascribed to intramitochondrial StAR, but the manner by which StAR promotes P450c11AS activity is unclear. As P450scc was undetectable, and circulating concentrations of corticosterone approached the Km (~28 μM) for the use of corticosterone as a substrate for P450c11AS, we suggest that cardiac P450c11AS uses circulating steroids for substrate. Thus the stressed heart produces aldosterone using a previously undescribed intramitochondrial mechanism that involves P450c11AS, Tom22 and StAR
SAT-747 A Prospective Non-surgical Treatment for Inguinal Hernias
Authors: Potluri Tanvi , Zhao Hong , Taylor Matthew Joseph , Bulun Serdar E 
Published: May 2020

Abstract
BACKGROUND: Inguinal hernias are a widespread public health issue and typically diagnosed in one-fourth of all men. Despite hernia repair being the most commonly performed surgery in the US, the mechanisms causing this disease are currently unknown. We previously developed a mouse model that expresses the human aromatase gene (Aromhum) wherein all male mice develop inguinal hernias. We further showed that high production of estradiol by aromatase in the lower abdominal muscle (LAM) via binding to estrogen receptor caused increased fibroblast proliferation and muscle atrophy which leads to inguinal hernia formation (1).
Hypothesis: Disruption of estrogen signaling via ablation of estrogen production using an aromatase inhibitor or inhibition of estrogen receptor by an estradiol antagonist can prevent or reverse the formation of inguinal hernias.
Results: We previously demonstrated that aromatase inhibitor, letrozole, completely prevented the formation of inguinal hernias in Aromhum mice (1). Here we show that ER-dependent estradiol antagonist fulvestrant can also prevent LAM tissue fibrosis, muscle atrophy and hernia formation in Aromhum mice (n=4, p=0.0007). WT littermates did not show hernia formation with or without fulvestrant treatment (n=4). Furthermore, we demonstrate that aromatase inhibitor letrozole can reverse mild to moderate size of hernia (150-160 mm2), while placebo-treated mice had progressively enlarged hernias (n=7, p=0.04). We subsequently show a reduction in muscle fibrosis and a restoration of myocyte size in Aromhum mice with letrozole treatment.
Conclusion: Estrogen produced as a result of aromatase expression in estrogen-sensitive LAM tissue stimulates the proliferation of estrogen receptor-expressing fibroblasts, fibrosis, muscle atrophy, and hernia formation. Ablation of estrogen production or its signaling not only completely prevents this phenotype but also reverses mild to moderate-sized hernias. Our findings pave the pathway for developing the first potential preventive and therapeutic pharmacological approach for combating recurrent inguinal hernias in elderly men through modulation of estrogen signaling in abdominal muscle tissue.
Reference: (1) Zhao H, et al.,PNAS. 2018 Oct 30;115(44):E10427-36.
MON-265 Once-Weekly Somapacitan in Japanese Adults with GH Deficiency Was Well Tolerated, with Similar Efficacy to Daily GH: A Randomized Trial
Authors: Otsuka Fumio , Takahashi Yutaka , Tahara Shigeyuki , Rasmussen Michael Højby , Ogawa Yoshihisa , Takano Koji 
Published: May 2020

Abstract
Somapacitan is a long-acting, reversible albumin-binding human growth hormone (GH) derivative based on a proven protraction technology. The objective of this trial was to evaluate the safety, efficacy and treatment satisfaction of once-weekly somapacitan compared with daily GH (Norditropin®) over 52 weeks in Japanese patients with adult GH deficiency (AGHD).
This was a phase 3, multicenter, randomized, open-label, parallel-group, active-controlled trial (NCT03075644). Patients previously treated with human GH were randomized 1:3 to either daily GH or somapacitan, respectively, to undergo 20 weeks of dose titration and 32 weeks of fixed-dose treatment. The primary endpoint was the incidence of adverse events (AEs) from baseline to week 53. Secondary endpoints included change from baseline in visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT, respectively) assessed with computerized tomography scans; change from baseline in treatment satisfaction evaluated using Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores; and occurrence of anti-somapacitan antibodies.
In total, 62 patients were randomized (16 to the daily GH and 46 to the somapacitan treatment arm), of which 60 completed the trial. Baseline characteristics for daily GH vs somapacitan groups, respectively, were: 43.8% vs 47.8% female, 87.5% vs 80.4% adult-onset GH deficiency, mean (SD) age 49.3 (11.5) vs 54.1 (12.1) years, weight 67.9 (12.0) vs 69.4 (22.7) kg, body mass index 24.8 (3.7) vs 26.4 (6.7) kg/m2, and GH dose at screening 0.29 (0.14) vs 0.31 (0.17) mg. Rate of AEs per 100 patient-years was similar between treatment arms (309.8 for daily GH, 312.7 for once-weekly somapacitan); most AEs were mild (97.9% and 93.1%, respectively) and none were severe. Four AEs in the somapacitan arm were serious; all were considered unlikely related to treatment. No anti-somapacitan antibodies were detected during treatment. Mean insulin-like growth factor-I standard deviation score (IGF-I SDS) at baseline was maintained with both treatments. The majority of the patients had IGF-I SDS values below +2. No significant differences in VAT, SAT and TAT were seen in both treatment groups after 52 weeks (estimated difference, somapacitan – daily GH [95% CI]): –1.74 [–18.13; 14.66], –11.53 [–35.54; 12.48], and –12.85 [–47.31; 21.62] cm2, respectively. TSQM-9 scores were not significantly different between treatments, but showed a tendency in favor of somapacitan (estimated difference [95% CI]): 4.87 [–3.46; 13.20] for effectiveness, 6.79 [–1.04; 14.61] for convenience, and 6.88 [–1.08; 14.85] for overall satisfaction.
No new safety concerns were identified. Improvements in body composition were similar in the GH and somapacitan cohorts. The safety and tolerability of somapacitan in Japanese patients with AGHD were consistent with results from the global phase 3 trial (REAL 1).
OR22-01 NF-κB Pathway Is Implicated in Thyroid Embryogenesis
Authors: Vanier Stéphanie Larrivée , Magne Fabien , Jean-Louis Martineau , Samuels Mark E , Van Vliet Guy , Deladoey Johnny Yvan 
Published: May 2020

Abstract
BACKGROUND: Congenital hypothyroidism due to thyroid dysgenesis (CHTD) is the most common congenital endocrine disease with a prevalence of 1:4,000 live births. We have suggested a two-hit hypothesis to explain CHTD, combining an inherited or de novo variant with a post-zygotic event. This model could explain the sporadicity of the disease (99%), its ethnic predominance and the high discordance rate between monozygotic twins. Despite years of research, more than 95% of cases of CHTD remain unexplained, especially those with thyroid ectopy. This suggests that research on genes and/or pathways not previously associated with thyroid development need to be pursued. Inactivation of the NF-κB pathway can cause deficient anterior pituitary and variable immunodeficiency, or DAVID syndrome. Whether this pathway is also involved in CHTD remains to be established. Objective: To evaluate the implication of the NF-κB pathway during thyroid migration. Methods: Knock down experiments using morpholinos in a zebrafish model were carried out to investigate the roles of certain genes related to the NF-kB pathway during thyroid development. Rescue experiment was also performed to evaluate the specificity of the morpholino. The first gene to be tested was IKBKE, a member of the inhibitor of κB kinase (IKK) family. Thyroid location was assessed by microscopy of live larvae. Results:ikbke depletion in zebrafish caused defective aortic arch artery formation and abnormal thyroid migration. The thyroid phenotype was partially rescued by injection of human IKBKE RNA in ikbke morphants. Conclusion:IKBKE seems important for normal thyroid migration suggesting that the non-canonical NF-kB pathway might be implicated. Further studies targeting other genes in this pathway are ongoing to extend these results.
SAT-035 In Vitro Effect of Different Follicle-Stimulating Hormone Preparations on Sertoli Cells
Authors: Grande Giuseppe , Iva Arato , Barrachina Ferran , Bellucci Catia , Cinzia Lilli , Jodar Meritxell , Chiara Aglietti Maria , Mancini Francesca , Vincenzoni Federica , Pontecorvi Alfredo , Calafiore Riccardo , Oliva Rafael , Luca Giovanni , Mancuso Francesca , Milardi Domenico 
Published: May 2020

Abstract
Follicle-stimulating hormone (FSH) is the main regulator of spermatogenesis and plays a key role in the development and function of the reproductive system. To assess the effects of different FSH preparations in combination with testosterone on porcine pre-pubertal Sertoli cells, we performed Real Time PCR analysis of AMH, inhibin B and FSH-r, Western blotting analysis of AKT-posphoAKT, ERK1/2-posphoERK1/2, ELISA assay for AMH and inhibin B and a high-throughput proteomic analysis.We observed that all three preparations induced a reduction of AMH in terms of mRNA and secreted protein and, an increase of inhibin B in terms of mRNA in all the formulations while, only α-follitropin induced an increase of inhibin B secreted in the culture medium. Proteomic analysis permitted us to identify 46 secreted proteins.Of those, the SPARC protein was down-regulated after the treatment with testosterone associated with α-follitropin, β-follitropin and urofollitropin (vs group stimulated with T alone). 11 proteins were up-regulated by the different FSH preparations. In detail, Hemoglobin subunit beta, TPA and TPI have been observed to be up-regulated by stimulation with testosterone in addition with α-follitropin or with β-follitropin and or with urofollitropin. All preparations induced an increase in the secreted inhibin beta A chain, but in the medium after stimulation with urofollitropin we observed an higher increase in the levels of this protein. β-follitropin, associated with testosterone, specifically induces an up-regulation of 8 specific secreted proteins.Our study, showing that the three FSH preparations were associated with different effects, could offer the opportunity to shed light inside applications to personalized reproductive medicine.