bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT147 A Pharmacist Driven Active Surveillance Program To Reduce Hypoglycemic Recurrences In The Inpatient Setting
Authors: Kim Steve , Tran Hai , Gianchandani Roma Yogesh 
Published: October 2023

Abstract
Disclosure: S. Kim: None. H. Tran: None. R.Y. Gianchandani: None.
Background: Hyper and hypoglycemia increase morbidity and mortality in hospitalized patients. Glucose excursions are time sensitive and require timely response to prevent future episodes of dysglycemia. As part of a quality improvement initiative, we implemented an Active Glycemic Surveillance (AGS) program in July 2022 targeting patients with hypoglycemia (BG &lt;70 mg/dL) based on a preliminary evaluation that revealed recurrent hypoglycemia was an opportunity for improvement. Pharmacist involvement in glycemic management has been shown to improve clinical outcomes in the acute care setting. Our AGS program is unique in that pharmacist trained in inpatient glycemic management is empowered to directly intervene on antihyperglycemic medication orders under scope of practice by a protocol approved through the pharmacy and therapeutics committee.
Intervention: The AGS team consists of an endocrinologist and a diabetes stewardship pharmacist. A policy was developed and approved by P and T that outlines the types of interventions and orders that the diabetes stewardship pharmacist is able to make under scope of practice. These interventions include the ability to order certain labs (POCT BG, HgbA1C), and to adjust or discontinue certain anti-hyperglycemic agents Hospitalized patients who have a BG &lt;70 mg/dL in the last 24 hours are reviewed by the AGS team. Chart review is performed on each patient to identify contributing factors and complicated cases are discussed with the endocrinologist prior to contacting the providers or making changes to orders. Providers are given rationale for changes as well as any other recommendations related to glycemic management. Results: During a 3 month period between August and October 2022, 848 cases of hypoglycemia were evaluated. Of these, 450 (53%) were found to be caused by an antihyperglycemic agent and 401 interventions were made by either the AGS team or other providers. The AGS team made 167 (41.6%) interventions and had a 24 h recurrence rate of 8.3% compared to 16.3% for all other providers. The most common types of interventions made by the AGS team were adjusting the insulin correction scale (78), basal insulin (57), bolus/meal insulin (16), oral medications (10), and TPN insulin (3). Conclusion: Our preliminary data show that a pharmacist-driven active surveillance program can reduce hypoglycemic recurrences. In the short time our AGS program has been implemented we have seen in increased utilization of appropriate correction scales, a decreased reliance on basal insulin or correction scale as the sole means of glycemic management, and an increase in endocrinology consultation for glycemic guidance. Future data will show the impact of this program on our overall hypoglycemia and hyperglycemia rates in future.
Presentation: Saturday, June 17, 2023
SAT150 "Sawtooth" Hypoglycemia: Rare Case Of IGF-2 Mediated Hypoglycemia With Elevated Proinsulin Level And "Sawtooth" Pattern On CGMS
Authors: Goparaju Pruthvi , Zena Mohsen 
Published: October 2023

Abstract
Disclosure: P. Goparaju: None. M. Zena: None.
Background: IGF-2 mediated hypoglycemia is usually associated with low Insulin, C-peptide and Proinsulin levels. We present an extremely rare case of IGF-2 mediated hypoglycemia with elevated Proinsulin level and an unusual “saw tooth” pattern on Continuous glucose monitoring system(CGMS). Clinical Case: 53-year-old male with history of metastatic Liposarcoma was admitted to the hospital with severe hypoglycemia. Whipple’s triad was positive on presentation, patient had symptoms of altered sensorium, blood glucose of 24 mg/dl, and symptoms improved upon correction of hypoglycemia. The patient was admitted to the ICU and IV dextrose was initiated.As Liposarcomas are known to be associated with Non-islet cell tumor hypoglycemia (NICTH), treatment with Prednisone was started. Prior to this, initial hypoglycemia workup was sent when blood sample was drawn during a hypoglycemia episode. Patient has no personal or family history of Diabetes. Adrenal insufficiency was ruled out with morning cortisol of 17.8 ug/dl. Serum glucose was low at 40mg/dl, Insulin&lt;1(0-17 pmol/L), C-peptide level low at 0.4 (0.8-3.9 ng/ml), IGF-1 level was low at 68 (74-225 ng/ml), normal IGF-2 at 626 (333-967 ng/ml) and increased IGF-2/IGF-1 ratio of 9.2(Normally around 3:1). All the lab work above is consistent with IGF-2 mediated hypoglycemia with low Insulin, C-peptide and IGF-1 levels and increased IGF-2/IGF-1 ratio. Interestingly, he has an elevated Proinsulin level of 36.9 (0.0-10.0 pmol/L) which is very unusual.Prednisone was started at 20mg daily to which there was reasonable response, dose was eventually increased to 60mg daily before he was safely sent home. He was discharged on a CGMS and the data was downloaded 2 weeks later. He had an interesting “Saw tooth” pattern of glycemia on the daily glucose graphs. As the patient had access to live data, he was trying to correct the falling blood glucose which briefly improved the readings but was quickly followed by another drop and this sequence carried on leading to a unique blood glucose pattern on the CGMS. Conclusion: Proinsulin level is usually suppressed in IGF-2 mediated hypoglycemia. Our case is unusually associated with high Proinsulin level. One hypothesis is the possible structural similarities leading to lab assay interactions between Proinsulin and “Pro-IGF-2”, which is thought to be one of the main molecules responsible for hypoglycemia in this condition. More studies in future will be helpful to study this possible association. Our case also had a remarkable “Saw tooth” pattern on CGMS glucose graphs which is very rarely seen in clinical practice.
References: Dynkevich, Yevgeniya et al. “Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive.” Endocrine reviews vol. 34,6 (2013): 798-826. doi:10.1210/er.2012-1033
Presentation: Saturday, June 17, 2023
SAT169 Sugar Crash: A Case Of Recurrent Hypoglycemia
Authors: Malvar Cyerwin Monique T , Patel Pooja , Moran Heberth , Bleich David 
Published: October 2023

Abstract
Disclosure: C.T. Malvar: None. P. Patel: None. H. Moran: None. D. Bleich: None.
Introduction: Post-prandial hypoglycemia is a rare complication following Roux-en-Y gastric bypass surgery (RYGB). Some theories suggest that post-operative beta cell expansion and altered beta cell function may lead to increased secretion of insulin, thereby causing hypoglycemia. We report a 39-year-old female with multiple episodes of recurrent post-prandial hypoglycemia following RYGB. Case Report: A 39-year-old female with a past medical history of type 2 diabetes managed with insulin, hypertension, hyperlipidemia, and obesity underwent RYGB and developed multiple episodes of fatigue, diaphoresis, palpitations, and tremulousness a year later. The patient continued to have worsening symptoms, leading to multiple hospitalizations for hypoglycemia. During her initial presentation to the emergency department, she was found to be afebrile, tachycardic with stable blood pressure. Work up revealed a glucose of 34 mg/dl (70 - 109 mg/dl), insulin of 40.1 (2.6 - 24.9 uIU/mL), C-peptide of 3.8 (1.1 - 4.4 ng/mL), potassium of 3.2 (3.5 - 4.8 meq/l), negative sulfonylurea screen, normal renal function, and a mild leukocytosis of 12.6 (4.0 - 11.0 x 10*3/µL). CT abdomen/pelvis, chest x-ray, and urinalysis were normal and did not reveal any infection. The patient denied taking any hypoglycemic agents and reported consuming high glycemic index meals. During her hospitalization, she received a bolus of dextrose followed by a continuous dextrose drip; however, she continued to experience recurrent hypoglycemic events requiring glucagon and dextrose tablets. Subsequent morning labs showed elevated insulin levels at 34.6 (2.6 - 24.9 uIU/mL) and a normal IGF-1 level. Her 8AM cortisol level was 2.3 (6.0 - 18.4 ug/dl). Due to high suspicion of adrenal insufficiency, she was started on Hydrocortisone. Pituitary MRI was negative for any adenoma. Hydrocortisone was held and a cosyntropin stimulation test established appropriate adrenal response. Hydrocortisone and dextrose tablets were discontinued. She was educated on eating low glycemic index meals to prevent future hypoglycemic episodes. She was started on acarbose as it delays carbohydrate degradation, thereby preventing reactive hypoglycemia. Conclusion: This case highlights the importance of having a thorough differential diagnosis in patients with a history of bariatric surgery and hypoglycemic episodes including adrenal insufficiency, which in this case was ruled out. RYGB increases stimulation of islet β-cells by enteral signals and enhances GLP-1 sensitivity and insulin secretion, predisposing some individuals to hypoglycemic episodes. Patients may have remission of diabetes and no longer need medications post-operatively. Dietary modification is fundamental in the management of hypogylcemia after RYGB. Pharmacotherapy is an adjunctive treatment if symptoms persist.
Presentation: Saturday, June 17, 2023
OR06-03 Intergenerational Exposure To Endocrine-disrupting Chemicals (Edcs) Affects Dopamine-mediated Behaviors In A Sex-Specific Manner In Rats
Authors: Hilz Emily N , Schnurer Cameron , Bhamidipati Swati , Thompson Lindsay , Morales-Ledesma Ellyzabeth , Gore Andrea C 
Published: October 2023

Abstract
Disclosure: E.N. Hilz: None. C. Schnurer: None. S. Bhamidipati: None. L. Thompson: None. E. Morales-Ledesma: None. A.C. Gore: None.
Polychlorinated biphenyls (PCBs) are a weakly estrogenic class of ubiquitous environmental EDCs that affect a range of sex-specific neuroendocrine and reproductive outcomes. Furthermore, these effects can extend intergenerationally via epigenetic changes carried down the germline. In humans, PCBs are associated with sexually dimorphic and hormone sensitive neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD) and mood disorders such as depression; however, little preclinical work has modeled these cognitive changes in rats and none has determined if they extend intergenerationally via endocrine-mediated changes to the brain dopamine system. In the current work, three generations of male and female Sprague-Dawley rats were exposed to the PCB mixture Aroclor 1221 (A1221) at different life stages: as adults; through perinatal exposure via mother's diet; or preconceptionally, as the germ cells within the exposed fetus. Adults of each generation underwent a battery of behavioral tasks to assess attentional phenotype, cognitive flexibility, and affect as measured by attentional set-shifting, conditioned orienting, and sucrose preference tests. These outcomes were correlated with both serum estradiol concentrations and dopamine cell quantity in the midbrain. Results revealed that A1221 treatment had sex- and generation-specific effects: in adult-exposed females, decreased conditioned orienting suggested a hyporesponsive attentional phenotype; in males, preconceptional exposure reduced cognitive flexibility via impaired attentional set-shifting. All rats showed a strong preference for sucrose solution; however, A1221 treatment decreased the total amount of sucrose solution consumed (indicating anhedonia) regardless of sex or timing of exposure. Dopamine cell numbers were inversely affected by A1221 between the sexes: decreased in females and increased in males, which correlates well with the cognitive changes observed. Relationships among estradiol concentration, cognitive changes, and dopamine cell quantity will be ascertained using a multilevel model that accounts for endocrine-mediated disruptions at the brain, body, and behavioral levels. These data show that the PCB mixture A1221 impairs different aspects of cognitive behavior between the sexes depending on timing of exposure, while having a broader effect of increased anhedonia, in a manner potentially mediated by hypo- or hyper-availability of midbrain dopamine and serum estradiol. Supported by RO1 ES029464.
Presentation: Thursday, June 15, 2023
SAT438 Nivolumab Induced Endocrinopathies- Outcomes And Learning
Authors: Kethireddi Keerthi Madhurya , Jhetam Suhail , Parthasarathy Sathish Babu 
Published: October 2023

Abstract
Disclosure: K. Kethireddi: None. S. Jhetam: None. S.B. Parthasarathy: None.
Background: Nivolumab is an anti PD-1 mAB (Programmed Cell Death protein) used in the treatment of melanoma, renal, head & neck and other cancers. Use of Nivolumab either as a single therapy or in combination with other immune check point inhibitors (CPI) like Ipilimumab, Pembrolizumab often results in immune mediated endocrinopathies. Existing literature on Nivolumab indicates median time to the onset of hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, and hypophysitis as 1.5 months, 2.9 months, 4.4 months and 4.9 months respectively. Our objective is to add to the existing body of knowledge, compare local data on presentation and other variables of these endocrinopathies with recommendations to improve diagnosis and access to treatment of these endocrinopathies. Design: It is a retrospective analysis of the patients who received Nivolumab (single or combination therapy) between 2019 and 2022 in our hospital. Methodology: A total of 83 patients were treated either with single therapy Nivolumab (n=44) or combination therapy (n=39) and were screened for immune endocrine toxicities. Data was collected mainly from hospital based clinical software for routine use. Data was also collected on prior endocrine tests such as Hba1c and Thyroid function, if done prior to commencement of immunotherapy. Major results: Nineteen patients (23%) developed immune related endocrinopathies which included Thyroiditis/hypothyroidism (n= 12) followed by adrenalitis (n= 6), Type 1 Diabetes (n=1) and hypophysitis (n=3). Onset of thyroid dysfunction occurred between 4 to 8 weeks, adrenalitis between 8 to 32 weeks, hypophysitis between 4 weeks to 12 weeks and 24 weeks for type 1 diabetes mellitus. All patients were appropriately counselled and were provided with Patient Information leaflet. Regular screening bloods (Hba1c, Glucose, Cortisol and Thyroid function tests) were requested in most patients. Emergency presentations of Diabetic ketoacidosis (n=1) and Adrenal insufficiency (n=2) were noted with no mortality. Conclusion: 23% of the patients on Nivolumab had immune mediated endocrinopathy with Thyroiditis/Hypothyroidism being the commonest and the earliest endocrine abnormality. A Standard Operating Procedure for acute endocrine emergencies post Immunotherapy based on Society for Endocrinology guidance, needs to be implemented with education to create greater awareness given the expected high prevalence of these endocrinopathies post Immune CPI therapies. We recommend oral steroid (prednisolone/hydrocortisone) rescue pack and patient education on SMBG (Self-monitoring of blood glucose) as a part of sick day rule management in these patients and we believe this to be lifesaving and resource saving measure given the critical nature of these endocrine emergencies post immune CPI therapies.
Presentation: Saturday, June 17, 2023
SAT441 Association Of PFOS Exposure And The Risk Of Coronary Artery Disease In Postmenopausal Women
Authors: Eve Alicia Arredondo , Tunc Elif , Mehta Dhruv , Erbak-Yilmaz Huriye , Emren Sadik Volkan , Akyildiz-Akcay Filiz , Erdogan Zeynep Madak 
Published: October 2023

Abstract
Disclosure: A. Arredondo Eve: None. E. Tunc: None. D. Mehta: None. H. Erbak-Yilmaz: None. S. Volkan Emren: None. F. Akyildiz-Akcay: None. Z. Madak Erdogan: None.
Cardiovascular diseases (CVD) are the number one cause of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Perfluoroalkyl substances (PFAS) are a class of highly fluorinated chemicals used in our daily household necessities and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Perfluorobutanesulfonic acid (PFBS) in postmenopausal women from our previously established CVD cohort using liquid chromatography with tandem mass spectrometry (LC-MS-MS) analysis and supported by machine learning approaches. Here we show that PFOS levels were significantly higher in postmenopausal women with coronary cardiovascular disease (CAD) when compared to control and coronary microvascular disease (CMD) group. We also found that specific metabolite concentrations (alanine, isoleucine, proline, and tyrosine) were negatively associated with serum PFOS levels. A significant correlation with changes in the expression of proteins such as growth hormone (GH), tyrosine-protein kinase Mer (MERTK), metalloproteinase inhibitor 4 (TIMP4), transferrin receptor protein 1 (TFRC), thrombospondin-2 (THBS2) and PFOS was observed. Our findings may provide new insight into the potential mechanism underlying the increased risk of cardiovascular events in postmenopausal women and the emerging evidence on PFAS-induced risk of cardiovascular diseases in this vulnerable population.
Presentation: Saturday, June 17, 2023
OR01-05 Growth Hormone Action In Somatostatin Neurons Regulates Anxiety And Fear Memory
Authors: dos Santos Willian O , Juliano Vitor A L , Vieira Henrique R , Frazao Renata , Munhoz Carolina Demarchi , Donato Jose 
Published: October 2023

Abstract
Disclosure: W.O. dos Santos: None. V.A. Juliano: None. H.R. Vieira: None. R. Frazao: None. C.D. Munhoz: None. J. Donato: None.
Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and depression. Furthermore, GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of post-traumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence neuropsychiatric diseases. Here we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SSTΔGHR mice) led to increased anxiety in the light-dark box and elevated plus maze tests, whereas SSTΔGHR females showed no changes in anxiety, compared to control animals. Using auditory Pavlovian fear conditioning, both male and female SSTΔGHR mice exhibited a significant reduction in fear memory. In contrast, GHR ablation in SST neurons did not affect memory in the novel object recognition test. The gene expression was analyzed in a bilateral micropunch comprising the central nucleus of the amygdala and basolateral complex of male mice. Increased mRNA expression of Gabbr2 (GABAB2 receptor), Syp (synaptophysin), and Bdnf were observed in the amygdala of SSTΔGHR mice. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not in female mice. GHR ablation in SST neurons also decreases fear memory and affects the gene expression in the amygdala. Our findings identified for the first time a specific neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases.
Presentation: Thursday, June 15, 2023
OR01-06 Single Nucleus Multi-omics Analysis Identifies Cellular Trajectories And Dynamic Changes In Gene Expression And Chromatin Accessibility In The Pituitary During The Mouse Estrous Cycle
Authors: Ruf-Zamojski Frederique Murielle , Cheng Wan Sze , Zhang Zidong , Zamojski Michel , Smith Gregory R , Chen Xi , Mendelev Natalia , Strupinsky Galia , Alonso Carlos Agustín , Gambino Luisina Ongaro , Zhou Xiang , Brule Emilie , Amper Mary Anne S , Hanna Pincas , Nair Venugopalan D , Andoniadou Cynthia Lilian , Turgeon Judith L , Troyanskaya Olga , Zaslavsky Elena , Bernard Daniel J , Sealfon Stuart C 
Published: October 2023

Abstract
Disclosure: F.M. Ruf-Zamojski: None. W. Cheng: None. Z. Zhang: None. M. Zamojski: None. G.R. Smith: None. X. Chen: None. N. Mendelev: None. G. Strupinsky: None. C.A. Alonso: None. L. Ongaro Gambino: None. X. Zhou: None. E. Brule: None. M.S. Amper: None. P. Hanna: None. V.D. Nair: None. C.L. Andoniadou: None. J.L. Turgeon: None. O. Troyanskaya: None. E. Zaslavsky: None. D.J. Bernard: None. S.C. Sealfon: None.
Single cell multi-omics datasets provide an unparalleled power to resolve gene regulatory circuits underlying cellular function in complex tissues such as the pituitary gland [1, 2]. To better understand cellular plasticity and dynamics in the mouse pituitary during the estrous cycle in vivo, we performed same-cell single nucleus (sn) multi-omics for gene expression and chromatin accessibility on individual pituitaries collected from mice at 9am on each day of the cycle, as well as at 6pm and 11pm on proestrus and at 2am on estrus to capture surge events. Cycle stage was determined by vaginal cytology and post-mortem measurement of serum LH and FSH levels. In total, 102,069 cells passed rigorous quality control (QC, [2]), with over 5,000 cells analyzed per sample, ∼2,000 genes/cell, ∼15,000 ATAC median high-quality fragments, and Transcription Start Site (TSS) enrichment scores above 9 for all samples. We identified 13 well-separated clusters in the snRNAseq and 10 in the snATACseq datasets representing the pituitary cell types that were followed over time. We integrated the gene expression and chromatin accessibility datasets and analyzed changes in cell type proportions, gene expression, and chromatin accessibility through time. We detected major differential gene expression changes in the gonadotropes and lactotropes, which we further investigated using pseudotime trajectory analyses. Several upstream Fshb loci showed dynamic changes during the estrous cycle. Additionally, we uncovered regulatory components of major pituitary genes over time using linkage data analysis.To our knowledge, this is the first study to present detailed and comprehensive data on gene expression and chromatin structure changes at sn resolution in all pituitary cell types during a dynamic physiological process. Thus, it provides critical new resources to the field of endocrinology.
References:[1] Nat Comm, 2020, 12(2677), PMID:33976139.[2] Cell Reports, 2022, 38(10): 110467, PMID:35263594.
Presentation: Thursday, June 15, 2023