bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT612 Granulomatous Mastitis: An Unusual Presentation Of Prolactinoma
Authors: Alkaissi Hussam R , Kim Emily , McFarlane Samy 
Published: October 2023

Abstract
Disclosure: H.R. Alkaissi: None. E. Kim: None. S. McFarlane: None.
Background: Granulomatous mastitis (GM) is a rare, benign inflammatory breast disease of unclear etiology with clinical presentation that is similar to inflammatory breast cancer and periductal lobular mastitis. It occurs mainly in younger females and during the postpartum period. Prolactin (PRL) is an essential hormone of pituitary and extrapituitary origin that promotes lactation and the development of mammary glands within breast tissues. In addition to its lactogenic effect, it has over 300 other effects, several of which are immunomodulatory, including the expression and secretion of proinflammatory cytokines from macrophages. Clinical Case: A 37-year-old African American woman presented with right breast pain and swelling for a few weeks. Her medical history includes amenorrhea for five years. She is gravida 1, para 1 with normal spontaneous vaginal delivery at the age of 20. Physical exam showed non-bloody, non-purulent nipple discharge bilaterally, otherwise unremarkable. A breast ultrasound showed a 1 cm complex cystic mass. Biopsy showed benign breast tissue, with noncaseating granulomas formed by macrophages (CD68 positive on immunohistochemistry). Ziehl-Neelsen staining for acid-fast bacilli was negative. Staining for fungi was also negative. Prolactin level was 237 ng/mL. TSH, IGF-1, and ACTH were within normal. Pituitary MRI showed a focus of abnormal signal and diminished enhancement measuring 2.8x3.2x4.2 mm within the left side of the pituitary gland is compatible with a microadenoma. The patient was started on bromocriptine 2.5mg daily. Discussion: Our patient represents a rare case of granulomatous mastitis in the setting of microprolactinoma, likely long-standing, given the five years history of amenorrhea. The immunomodulatory effect of PRL on several immune system cells, including B-cells, T-cells, and macrophages, might be an underlying mechanism. In a recent study of 25 samples of GM, metagenomics studies identified unusual organisms in 68% of the samples. Of these, Corynebacterium kroppenstedtii was the most common (60%), followed by Pseudomonas oleovorans (16%), Epstein-Barr virus (4%), Acinetobacter baumannii (4%), and Tepidiphilus thermophilus (4%). In addition, 50% of the patients had elevated PRL, and elevated immunological markers, such as C3 and IgA [1]. This suggests that GM results from an interaction between the presence of certain pathogens in a host with elevated PRL that mediates proinflammatory response.
References: 1. Bi J, Li Z, Lin X, et al. Etiology of granulomatous lobular mastitis based on metagenomic next-generation sequencing. Int J Infect Dis. 2021 Dec;113:243-250. doi: 10.1016/j.ijid.2021.10.019. Epub 2021 Oct 19. PMID: 34673215.
Presentation: Saturday, June 17, 2023
SAT619 Post-operative Fluid Restriction Prevents Hyponatremia And Readmissions After Pituitary Surgery
Authors: Chang Julia J , Veruttipong Darlene , Chu Olivia , Erin Wipff , Gates-Bazarbay Victoria , Kling Samantha , Vinluan Khristine , Chittum Shelli , Alhadha Mohamed , Fernandez-Miranda Juan 
Published: October 2023

Abstract
Disclosure: J.J. Chang: None. D. Veruttipong: None. O. Chu: None. W. Erin: None. V. Gates-Bazarbay: None. S. Kling: None. K. Vinluan: None. S. Chittum: None. M. Alhadha: None. J. Fernandez-Miranda: None.
Background: Delayed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion is the most common cause of readmission after pituitary transsphenoidal surgery (TSS). Post-operative fluid restriction (FR) after discharge may effectively reduce hyponatremia and related readmissions. Methods: Our aim was to assess the effectiveness of FR after TTS. We compared post-operative day (POD) 8 hyponatremia and related readmission rates pre- and post- FR protocol implementation at our institution. Pre-FR (July 1, 2018-March 15, 2020) post-TSS patients were instructed to drink ad lib or to thirst on discharge. Post-FR (March 16, 2020-December 31, 2020), post-TSS patients were routinely provided education and documentation on the outpatient protocol that recommended 1 liter/day FR from POD 3-5 to POD 8-10. Serum sodium was assessed at POD-8 for all patients. Patients hospitalized for more than 5 days after surgery, had untreated adrenal insufficiency, or had pre-existing AVP deficiency were excluded. Results: The average POD-8 sodium level was lower in the 115 patients in the pre-FR cohort than the 216 patients in the post-FR cohort (135.8±6.7 vs. 138.1±4.4 mEq/L; Wilcoxon-Mann-Whitney test p=0.0081). POD-8 hyponatremia (Na ≤134 mEq/L) occurred in a lower proportion of patients post-FR (15.0%; 32/214) than pre-FR (28.9%; 30/104) (Chi-Square test p=0.0033). Similarly, severe hyponatremia (Na ≤124 mEq/L) occurred in a lower proportion of patients post-FR (1.4%; 3/214) than pre-FR (8.7%; 9/104) (Fisher test p= 0.01). Only 1.4% (3/216) of patients were readmitted post-FR compared to the 8.7% (10/115) pre-FR (Fisher test p=0.0020). Conclusions: Our retrospective evaluation showed that implementation of post-TSS FR protocol significantly decreased hyponatremia by nearly 50% and readmissions by over 80% compared to the prior standard of care of drink ad lib or to thirst. FR should be considered standard-of-care for eligible patients without ongoing AVP deficiency to reduce hyponatremia and readmission burden to both patient and healthcare system.
Presentation: Saturday, June 17, 2023
OR2801 Novel Cis-Regulatory Mechanisms Of Lhb Transcription By Non-Coding RNAs And Non-Canonical DNA Structures
Authors: Refael Tal , Gruber Hadas , Golan Gil , Pnueli Lilach , Melamed Philippa 
Published: October 2023

Abstract
Disclosure: T. Refael: None. H. Gruber: None. G. Golan: None. L. Pnueli: None. P. Melamed: None.
Expression of the Lhb gene was shown previously to be directed by synergistic actions of lineage-specific transcription factors at conserved regions of the proximal promoter. However extensive genomic analysis during the last few decades has expanded the repertoire of factors we now know to be involved in transcriptional regulation, revealing roles for distal transcriptional enhancers and long non-coding RNAs (lncRNAs), whose modes of action are only beginning to be elucidated1. Recently it has also become evident that regulatory regions of the genome are enriched with non-canonical DNA structures. These include G-quadruplexes (G4s) which form on guanine-rich stretches of single-stranded DNA and iMotifs (iMs) on the complementary strand, and are reported to bind various proteins which presumably regulate and mediate their actions. We identified in available mice pituitary scATAC-seq data a region of gonadotrope-specific open chromatin upstream of the Lhb gene, and chromatin conformation capture (3C) in murine gonadotrope cell lines indicated the distal sites that are in physical proximity to the Lhb promoter. Further, we show by chromatin immunoprecipitation (ChIP) a peak of H3K4 monomethylation (H3K4me1) ∼3 kbp upstream of the Lhb TSS, and transcription of two bi-directional non-coding enhancer RNAs (eRNAs), both of which are characteristic of transcriptional enhancers. One of the eRNAs was found to direct open chromatin at the Lhb promoter and is required for Lhb transcription, while guide RNA-mediated recruitment of dCas9- KRAB or dCas9-VP64 to this locus altered Lhb mRNA levels accordingly, confirming its functional enhancer activity. However this enhancer activity is not sufficient for optimal Lhb transcription, and we found that splicing in situ of a distinct downstream lncRNA is also required. The DNA at the central non-coding region of the enhancer, and at the promoter of this lncRNA, forms G4 and iM structures, seen by circular dichroism and ChIP. These DNA structures are affected differentially by local conditions including changes in pH or hormonal treatments, and appear to have diverse effects. HMGB2, which is known to bind structured DNA, was found to bind the enhancer iM in cells and in vitro. Further, HMGB2 knockdown reduced the iM signal and Lhb mRNA, eRNA and lncRNA expression levels quite dramatically. We thus present novel elements involved in the regulation of Lhb transcription through various classes of non-coding RNAs and DNA structures, while emphasizing the complexity of transcriptional regulation via context-dependent cis-acting elements. References: 1. Refael T, Melamed P. (2021). Enhancing gonadotrope gene expression through regulatory lncrnas. Endocrinol. (United States) 162, bqab116.
Presentation: Sunday, June 18, 2023
THU580 A Subset Of Migrating Cells Co-express Gonadotropin Releasing Hormone And Prokineticin Receptor 2 During Embryonic Development
Authors: Danku Antoinette Eyram , Elias Carol F 
Published: October 2023

Abstract
Disclosure: A.E. Danku: None. C.F. Elias: None.
A subset of migrating cells co-express gonadotropin releasing hormone and prokineticin receptor 2 during embryonic development Antoinette Danku and Carol F Elias. Neuroscience Graduate Program and Department of Molecular & Integrative Physiology, University to Michigan. Reproductive vitality in humans is strongly influenced by developmental foundations. The successful migration of GnRH cells and the pulsatile secretion of gonadotropin releasing hormone (GnRH) drives pubertal onset and dictates long-term fertility outcomes. During development, GnRH neurons migrate from the nasal placode to the basal forebrain to reach their destination in the medial preoptic area (MPOA). Aberrant GnRH migration causes redirection of axonal projections to atypical brain regions and dysregulated GnRH secretion. Disruption of GnRH neuronal function causes infertility or reproductive dysfunction. These etiologies are grouped as isolated gonadotropin deficiencies (IGD). Kallmann’s syndrome (KS) is a pediatric IGD that manifests as anosmia and hormonal dysfunction that can result in pubertal delay or infertility. Children with KS often have mutations in prokineticin 2 (Prok2) or the cognate receptor (ProkR2).Prok2 and ProkR2 are required for the formation of the olfactory bulb in rodents and humans. Loss-of-function mutations in these genes also disrupts GnRH cell migration, but whether the activation of ProkR2 regulates the guidance of GnRH neurons to their final destination has not been defined. Previous studies suggested that GnRH and ProkR2 are expressed in distinct cells, but how the prokineticin system may alter GnRH migration is largely unknown. To gain insights into the underlying mechanisms associated with ProkR2-GnRH interaction and migration, we conducted single nuclei RNA sequencing in nasal-forebrain junction of embryos at embryonic day 16 (E16) and fluorescent in situ hybridization in three developmental time points: E14, E16, and E18 for validation and spatial evaluation. Using these methods, we were able to isolate GnRH and ProkR2 cells and sort their cell types into clusters. While these cells differ in their expression profiles, they both express genes associated with migration at E16. Our findings suggest that ProkR2 cells in the nasal-forebrain junction migrate along with GnRH cells. Additionally, a subset of these migrating cells co-express ProkR2 and GnRH mRNA. Further studies are needed to determine whether this subset of cells take on specialized roles in GnRH cell migration and maturation.
Presentation: Thursday, June 15, 2023
THU607 Improving Screening For Primary Aldosteronism Among People With Apparent Treatment Resistant Hypertension
Authors: Zekarias Kidmealem , Tessier Katelyn , Kohlenberg Jacob 
Published: October 2023

Abstract
Disclosure: K. Zekarias: None. K. Tessier: None. J. Kohlenberg: None.
Introduction: The screening rate for primary aldosteronism (PA) is low among people with resistant hypertension. People with PA experience significantly more cardiovascular complications than those with primary hypertension and an equivalent degree of blood pressure control1. Therefore, identification of people with PA for early-directed therapy is crucial. Objective: We aimed to improve the screening rate for PA among people with apparent treatment resistant hypertension (aTRH), defined as blood pressure &gt;140/90 despite the concurrent use of three antihypertensive drug classes or any person with hypertension on &gt;4 antihypertensive medications. Methods: Using an electronic medical record (EMR) best practice alert (BPA), we implemented a quality improvement (QI) program from 9/17/2022-3/16/2023. We included adults ≥18 years of age with aTRH, who were identified using ICD codes, the last three blood pressure measurements and the antihypertensive medication list. During office visits with nephrologists, cardiologists, endocrinologists, family medicine physicians, and internists, a BPA notified providers if the person with aTRH had not been previously screened for PA with plasma aldosterone and plasma renin activity. The alert defined aTRH, suggested that screening be performed regardless of active medications, and contained an order set for plasma aldosterone, plasma renin activity, and plasma potassium. Furthermore, the BPA suggested referral to an endocrinologist if the patient fulfilled criteria for positive case detection for PA, defined as plasma renin activity &lt; 1 ng/mL/hour and plasma aldosterone concentration (PAC) &gt; 10 ng/dL or the plasma aldosterone to renin ratio (ARR) &gt; 30 with PAC &gt; 10. We compared the PA screening rate after the implementation of the BPA to the PA screening rate over the 1 year prior to the BPA implementation (9/16/2021-9/16/2022). Results: Plasma aldosterone lab orders were placed for 3.4% (179/5,261) of people with aTRH post-BPA implementation compared to 1.9% (211/10,944) pre-BPA implementation (p&lt;0.01). Positive case detection for PA occurred in 25% (38/152) of people screened post -BPA implementation compared to 27% (47/173) pre-BPA implementation (p=0.66). People with aTRH who were younger (p&lt;0.01) were more likely to be screened for PA pre-BPA implementation and this did not change post-implementation. Conclusion: Implementation of a QI program employing a BPA with an embedded order set in the EMR improved the screening rate for PA among adults with aTRH. Reference 1. Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018 Jan; 6 (1):41-50.
Presentation: Thursday, June 15, 2023
THU130 Long Term Tracking Of HbA1c Levels Across The Life Span In Type 1 Diabetes: From Infants To Young Adults
Authors: Kim Sujin , Song Kyungchul , Lee Myeogseob , Seo Junghwan , Chae Hyun-wook , Kim Ho-Seong , Kwon Ahreum 
Published: October 2023

Abstract
Disclosure: S. Kim: None. K. Song: None. M. Lee: None. J. Seo: None. H. Chae: None. H. Kim: None. A. Kwon: None.
Objectives HbA1c is the most important monitoring value and generally used in diabetes. However, HbA1c may change across the life span according to growth and puberty. This study explores the long-term tracking of HbA1c from infants to young adults diagnosed with Type 1 Diabetes mellitus (T1DM) and analyzes the effects of HbA1c according to life span on complications. Method This retrospective study, included 289 patients (M, 43.0%; mean first visit age, 7.39±3.94 years old; mean followed up periods, 4.32±3.15 years) diagnosed with T1DM. The total of 6368 HbA1c values were analyzed. The distribution of HbA1c values according to age and life period was evaluated. In addition, the differences in mean HbA1c values according to sex and the use of continuous glucose monitoring (CGM) were analyzed. Furthermore, it was analyzed which HbA1c of life period has the most influence on occurrence of complications. Result The level of HbA1c was relatively high at the age of 1- to 2-years, and then decreased between 4 to 5-years. After 5 years of age, HbA1C gradually escalated and peaked at the age of 12- to 15-years, during puberty. Especially for girls, HbA1c increased dramatically during puberty between the age of 10- to 13-years, which was consistent with the physiologic insulin resistance. During in childhood to young adulthood, the mean HbA1c of CGM users was lower than that of non-users. The higher mean HbA1c during all ages affected the occurrence of complications. Intriguingly, the HbA1c level during adolescence was important for the occurrence of diabetic retinopathy. Conclusion HbA1c level change across life span, and peaked at pubertal stage, which consistent with physiologic insulin resistance during puberty. In addition, good glycemic control in adolescence may reduce the occurrence of diabetic retinopathy. Therefore, using CGM in adolescence may be helpful for glycemic control and prevention of diabetic complications.
Presentation: Thursday, June 15, 2023
THU143 A Novel Maternally Inherited GNAS Variant In A Family With Hyperphagia And Obesity
Authors: Purushothaman Preetha , Ramakrishnan Anand , Gevers Evelien F 
Published: October 2023

Abstract
Disclosure: P. Purushothaman: None. A. Ramakrishnan: None. E.F. Gevers: None.
Introduction: Heterozygous inactivating mutations in the maternal allele of the GNAS gene typically result in pseudohypoparathyroidism (PHP) characterized by developmental delay, short stature, obesity, hormone resistance and bone abnormalities. Recently, GNAS variants were also described in 1% of patients in the UK Genetics of Obesity cohort, resulting in reduced MC4R signalling. Here, we report another novel GNAS variant in family with hyperphagia and obesity and only mild features of PHP. Case: The proband presented at 6 years with hyperphagia and obesity from age 3 years. BMI was 30.4 (4.1 SDS) with height +1.9 SDS, and head circumference (HC) + 3.0 SDS. She had subtle brachydactyly, short toes and a café au lait patch. Developmental milestones and cognitive achievements were mildly delayed. Her 12-year-old brother [ height +2.1 SDS, weight +3.1 SDS, BMI 29.55 (2.9 SDS), HC +3.6 SDS] had been followed in an obesity clinic for a few years with hyperphagia, obesity, delayed developmental milestones and a recent diagnosis of autism. He also had subtle brachydactyly, as did the mother who was also obese (BMI 38.9) with a normal height but had normal cognition. Results: In the proband, initial investigations did not suggest hormone resistance. However, at 8.7 years, PTH was high [9.5 pmol/L (0.7-5.6)] with normal calcium and Vitamin D; TSH 6.6 mU/L (&lt;6), FT4 11.8 pmol/L (10.8 - 19.0). She had hyperlipidaemia and fatty liver. X-ray hand showed generalised mild brachydactyly with a short right fifth metacarpal. In the brother, PTH tested for the first time at 12.9 years was 18.4 pmol/L (1.6-6.9), calcium and vitamin D were normal; TSH 4.04 mU/L (&lt;4.2) and FT4 13.4 pmol/L. Next Generation Sequencing using the Cambridge Obesity gene panel detected a novel heterozygous (c.791A&gt;C, p.(Asn264Thr) variant in exon 10 of GNAS in the proband and subsequently in the mother and brother confirming maternal inheritance. This variant has not been reported in control databases (1000 Genomes, ESP, ExAC and gnomAD, Human Gene Mutation Database and ClinVar). The variant is in a highly conserved region susceptible to missense mutations and has been classified as pathogenic using ACMG and ACGS guidelines. Discussion: In conclusion, we describe a novel heterozygous inactivating GNAS variant c.791A&gt;C, p.Asn264Thr resulting in hyperphagia, obesity, developmental delay, macrocephaly, mild brachydactyly, tall stature and variable biochemical mild hormone resistance in 2 siblings and resulting in obesity, mild brachydactyly without cognitive impairment in the mother. These cases demonstrate the clinical heterogeneity of the monogenic disease. Clinical and biochemical screening for PHP and genetic screening for GNAS variants should be performed in patients presenting with obesity, even in the absence of classical signs of PHP, to reduce diagnostic delay.
Presentation: Thursday, June 15, 2023
THU148 Changes In Cortisol:Cortisone Ratio In Youth With Obesity One Year Following Sleeve Gastrectomy Compared To Non-surgical Controls.
Authors: López López Ana Paola , Tuli Shubhangi , Becetti Imen , Lauze Meghan , Pedreira Clarissa C , Bredella Miriam , Misra Madhusmita , Singhal Vibha 
Published: October 2023

Abstract
Disclosure: A.P. López López: None. S. Tuli: None. I. Becetti: None. M. Lauze: None. C.C. Pedreira: None. M. Bredella: None. M. Misra: None. V. Singhal: None.
Introduction: Glucocorticoid metabolites are associated with body composition measures and are altered with weight status. Metabolic and bariatric surgery (MBS) results in significant changes in weight and body composition. However, effects of MBS on glucocorticoid metabolites are unknown. Objective: To evaluate (i) changes in the cortisol:cortisone ratio [indicator of 11β-Hydroxysteroid Dehydrogenase (11 β -HSD) global activity] in youth with obesity 12 months after sleeve gastrectomy (SG) compared with non-surgical controls with obesity (NS), and (ii) associations of these changes with body composition changes. Methods: 60 participants 13-25 years old with obesity (44 female) were followed for 12 months. 28 participants underwent SG and 32 were followed with routine care (non-surgical, NS). Fasting blood was assessed for cortisol and cortisone using LC-MS as part of metabolomic analysis, and the cortisol:cortisone ratio calculated. Single slice MRI of the abdomen was performed to assess subcutaneous, visceral and total adipose tissue (SAT, VAT and TAT) and DXA for percent (%) body fat. Results: At baseline, groups did not differ for age or sex. SG vs. NS had higher median BMI [46.4 (41.0, 52.8) vs. 41.9 (37.9, 46.9) kg/m2, p=0.007] and % body fat [51.2 (47.8, 52.3) vs. 47.2 (39.0, 47.2) %, p=0.005)]. Groups did not differ for baseline VAT, SAT, TAT and cortisol:cortisone [10.47 (9.52, 13.86) vs. 11.05 (6.37, 14.79), p=0.58]. Significant reductions were noted over 12 months in BMI, BMIz, % body fat, TAT, VAT, SAT and VAT/SAT within the SG vs. NS groups (p ≤ 0.03). No within group changes in cortisol:cortisone over one year were noted in the NS group, but the ratio trended to decrease in the SG group [-1.40 (-5.08, 0.06), p=0.08]. No associations were found between changes in cortisol:cortisone and changes in body composition. Conclusions: The cortisol:cortisone ratio tended to decrease 12 months following SG. No associations were found between changes in the cortisol:cortisone ratio and body composition changes. Further studies with larger numbers of participants are necessary to confirm these findings.
Presentation: Thursday, June 15, 2023