bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-212 Interference in Serum Androstenedione Measured by LC-MS/MS in Newborns Samples
Authors: Lima-Valassi Helena Panteliou , Takitane Juliana , Silva Márcia Rodrigues , Alves Atecla Nunciata Lopes , Hayashi Giselle Yuri , Hadachi Sonia Marchezi , Bachega Tania A , Mendonca Berenice Bilharinho 
Published: May 2020

Abstract
Introduction: Liquid chromatography followed by mass spectrometry (LC-MS/MS) is considered the gold standard method to measure steroids. Newborn screening for congenital adrenal hyperplasia (CAH) involves measurement of 17α-hydroxyprogesterone (17-OHP) in blood dried spots by immunoassay. Because this testing has high false-positive rates, serum samples to measure 17-OHP, androstenedione, 21-desoxicortisol and cortisol simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS) are used for confirmatory test in our laboratory. Objective: To report an interference in androstenedione levels measured by LC-MS/MS assay in serum samples from newborns. Patients and methods: The method for androstenedione measurements was based on protein precipitation followed by a semi-automated and multiplexed on-line solid phase extraction coupled reverse phase separation and detection of underivatized analyte by tandem mass spectrometry. Among 312 samples 82 presented unexpected androstenedione results considering that 17OHP levels were &lt;5 ng/mL. These samples presented a high variability among 4 replicates (CV ranged from 20 to 133%). These samples also showed an inadequate ion ratio resulting in pseudo-elevated androstenedione, indicating a coeluition of an isobaric interferent. In routine samples from other patients this problem was not observed. Results: Since this fact suggests a possible interference in LC-MS/MS measurements and modification in chromatographic method was unable to resolve from the interference, alternative method for sample preparation was developed. Liquid-liquid extraction with diethyl ether was performed and eliminated the interference and provided substantial decrease in androstenedione values (9.3+12.94 ng/mL vs 5.2+9.59 ng/mL after extraction) with ion ration normalization and CV less 10% between replicates. The identity of this compound is still unknown. Therefore, it will be necessary additional studies to clarify this artifact. Conclusions: Although the measurement of androstenedione by reverse phase chromatography without derivatization followed by tandem mass spectrometry is the simplest and commonest approach to determine androstenedione, it is susceptible to interferences causing falsely elevated androstenedione levels in newborns.
SAT-669 CD40 Ligand Gene Mutation in Type 1 Diabetes Mellitus in a Saudi Consanguineous Family
Authors: Alzaman Naweed , Shamsi Monis Bilal , Samad Firoz abdul , Imam Syed Nazar , Alharbi Ghadeer , Zaitooni Deema 
Published: May 2020

Abstract
Introduction:
Type 1 Diabetes Mellitus (T1D) is a common autoimmune disorder. Investigating genetic factors that could turn the immune cells to auto-reactive are critical to our understanding of T1D. In this study genetic factors and the affected autoimmunity related molecular mechanisms in familial T1D with parental consanguinity were studied.
Materials and Method:
Whole Exome Sequencing (WES) was performed in a family with familial T1D. Sanger Sequencing was done to analyze segregation in affected and non-affected. Clinical and molecular aspects were also evaluated. Protein modeling and other in silico tools were used to identify probable impact of genetic abnormalities on the structure and function of protein.
Result:
We identified a novel homozygous substitution mutation at “c.379A&gt;T:p.Iso127Val” in CD40 Ligand (CD40LG) gene in diabetic siblings by WES. This change was found to be segregating in the affected and non-affected individuals by Sanger sequencing. Parents and non-diabetic siblings were found to be heterozygous carriers of the nucleotide change. The c.379A&gt;T is located within evolutionarily conserved locus of human genome. Functional prediction by Gene Ontology term analysis suggested that immune functions of CD40LG are compromised by this genetic change. Further, by protein-modeling analysis we identified that structure of ligand-binding domain of CD40LG protein, with which it interacts with other immune cells, may also be affected. In silico analysis revealed significantly reduced spatial inter amino acid distance between the site of genetic change and the ligand binding domain in mutant CD40LG.
Discussion:
Apoptotic elimination of developing auto-reactive T-cells, having the potential to generate an autoimmune response against pancreatic cells, is critical to prevent T1D. This apoptotic removal mechanisms, occurs in thymus and is dependent on highly specific interaction of cell surface molecules as CD40LG on developing T-cells, and the corresponding cell surface molecules on Antigen Presenting Cells (APC). In the diabetic individuals investigated in our study, the mutation in CD40LG gene, caused significant structural damage to its protein, due to which these interactions between mutant CD40LG (present on T-cells) and the corresponding CD40 (present on APC) were probably affected. This loss of interaction between CD40LG bearing T-cells and APC, probably led to escape of auto-reactive T-cells in to immune system, which further generated autoimmune response against the pancreatic tissue, precipitating to T1D among these individuals.
Conclusion
Genetic investigation of cell surface proteins in autoimmune cells and understanding their mechanism for development of autoimmunity offers prospects for the development of new therapeutic strategies in the approach to probable early diagnosis of T1D.
MON-009 GLUT1-Mediated Glycolysis Facilitates GnRH-Induced Secretion of Luteinizing Hormone
Authors: Nicholas Dequina , Knight Vashti , Tonsfeldt Karen , Terasaka Tomohiro , Molinar-Inglis Olivia , Stephens Shannon Brooke Zoe , Trejo Joann , Kauffman Alexander S , Mellon Pamela L , Lawson Mark A 
Published: May 2020

Abstract
Reproduction requires intensive energy expenditure, and energy availability impacts the function of the reproductive endocrine HPG-axis. Accordingly, the reproductive axis is suppressed during hypoglycemia. Circulating blood glucose can directly interact with gonadotropes within the highly vascular pituitary. Therefore, it is possible that gonadotropes may sense energy availability via the presence of glucose in the circulation and integrate this status with input from GnRH neurons to regulate hormone production. Gonadotropes dominantly express glucose transporter 1 (GLUT1) and increase glucose uptake in response to GnRH. Thus, we hypothesized that gonadotropes engage glycolysis in response to GnRH stimulation due to the high energy demand of protein synthesis required for LH production. We developed an approach to sort and successfully culture primary gonadotropes from wild type mice. Using this approach, we performed extracellular flux analysis and found that gonadotropes respond to GnRH by inducing GLUT1-mediated glycolysis that is independent of mitochondrial respiration. Knock-down of GLUT1 expression in the LβT2 gonadotrope cell line, glucose restriction, or treatment with the competitive inhibitor of glycolysis, 2-DG, diminished GnRH-induced LH secretion, indicating GLUT1 expression is necessary for maximal GnRH-induced LH secretion. We confirmed this observation in primary female mouse gonadotropes by limiting glucose availability which resulted in diminished basal LH and FSH secretion. Lastly, GLUT1 expression in the pituitary correlates with GnRH receptor expression and is increased during the LH surge in a mouse model. These results implicate glucose uptake through GLUT1 as permissive for gonadotrope secretion of LH and therefore reproductive function, especially the LH surge. We conclude that GLUT1-mediated glucose uptake is an important rate-limiting step in gonadotropin synthesis and operation of the HPG-axis.
SAT-540 Primary Aldosteronism Represents Earlier Myocardial Fibrosis Than Essential Hypertension by T1 Mapping
Authors: Wu Tao , Ren Yan , Cheng Wei , Wang Wei , Zhou Fangli , Chen Yucheng , Zhou Xiaoyue , Sun Jiayu 
Published: May 2020

Abstract
Introduction:
Primary aldosteronism (PA) is associated with cardiovascular disease and has increased cardiovascular morbidity. Several studies had demonstrated that PA shows more serious myocardial fibrosis compared with essential hypertension (EH) using late Gadolinium-enhanced (LGE) imaging [1, 2]. However, the early myocardial change may not be detected by LGE. Recently, cardiac MRI T1 mapping emerged to be a sensitive technique in detecting early changes of myocardium quantitatively. Our study aimed to demonstrate the early myocardial change in PA patients by applying the T1-mapping technique.
Method:
81 (male: 25; age: 48±12 years) PA[3] and 44 (male: 21; age: 47±14 years) EH patients diagnosed by the Department of Endocrinology and metabolism according to the 2016 TES guidelines for PA were recruited from September 2018 to May 2019. All the subjects underwent cardiac MRI examinations on a 3T MRI scanner (MAGNETOM Trio a Tim System, Siemens Healthcare, Erlangen, Germany), including steady-state free-precession (SSFP) cine imaging and modified Look-Locker inversion recovery (MOLLI) imaging for T1 mapping. Functional parameters were obtained from cine images by the Argus software (Siemens Healthcare, Erlangen, Germany).The mid-ventricular native T1 value was acquired using the QMass software (Medis, Leiden, The Netherlands). Native T1 value and cardiac function parameters were analyzed between the two groups. Differences of continuous variables were analyzed by Student’s t-test or Mann-Whitney U-test, and the relationships between native T1 value and physiological variables were analyzed by multiple linear regression method.
Results:
The age (PA: 48±12 years vs EH: 47±14 years; p=0.720) and BMI (PA: 25.06±3.73 vs EH: 25.17±2.83; P=0.874) between two groups had no significant differences. The PA group had a significant higher aldosterone/renin ratio (ARR) than those in the EH group (114.6 (48.7-474.8)ng/dl:ng/ml.h vs 7.6 (4.2-13.8) ng/dl:ng/ml.h; p&lt;0.001). All functional parameters including LVEDVI (PA: 78.66 (72.4-90.6) ml/m2 vs EH: 75.8 (64.3-85.8) ml/m2; p=0.054); LVESVI (PA: 31.7 (26.2-38.4) ml/m2 vs EH: 29.3 (24.9-36.2) ml/m2; p=0.152); LVEF (PA: 59.9 (53.3-65.0)% VS EH: 59.2(55.3-65.6)%; p=0.679); LVmassi (PA: 58.5(47.7-67.7) g/m2 vs EH: 54.9 (47.6-60.1) g/m2; p=0.463) had no differences between the two groups. However, native T1 values were higher in PA group than those in EH group (1227±40ms vs 1203±45ms). The multiple linear regression analysis showed that gender (Beta=-27.678, p&lt;0.001) and PA (Beta=-17.287, p=0.031) were independently related to the native T1 values.
Conclusion:
PA patients represent more severe and earlier myocardium damage and this might be related to cardiovascular morbidity. The T1-mapping technique in cardiac MRI is more sensitive to evaluate the left ventricular function and to detect the myocardial fibrosis in PA patients.
MON-097 Continuous Glucose Monitoring in Youth with Type 1 Diabetes; Parental Anxiety and Parent Defined Outcomes: Results of Follow up Surveys
Authors: Alkhaled Lina , O’Riordan MaryAnn , MacLeish Sarah A , Hazen Rebecca , Wood Jamie 
Published: May 2020

Abstract
Continuous glucose monitors (CGMs) can be helpful in management of type 1 diabetes (T1D). Our objectives were to explore parental reason for adding CGM to their child’s T1D management and to describe potential barriers to starting CGM. Prior to CGM initiation, the primary caregiver of a child with T1D completed validated questionnaires including Fear of Hypoglycemia Scale (FOH), State-Trait Anxiety Inventory (STAI), Problem Areas in Diabetes Scale (PAID), and an investigator developed questionnaire assessing primary reason for starting CGM. Surveys were repeated 3-8 months after adding CGM.
The results of the initial surveys reported elsewhere suggest that the most common reason for starting CGM is to improve glycemic control. Out of 32 participants who completed initial surveys and intended to start CGM on their child, only 43% (N=14) started using CGM during the 3-8 month follow up period. Reasons for not starting CGM included: not having the chance to start the process of having it approved by insurance in 64% (N=9), and difficulties getting insurance to approve CGM in 28% (N=4). One participant reported that despite insurance coverage, out of pocket expense was too much.
Wilcoxon Rank Sum tests were used to compare demographic variables between those that started and those that did not start CGM. Medians were used to report the results. There were no statistically significant differences between children who did and did not start CGM in terms of age (9.3 vs. 11.4 yrs, P=0.3), baseline HbA1c (8.1% vs. 9.4%, P=0.1), and diabetes duration (3.0 vs. 4.3 yrs, P=0.6).
In summary, despite parental interest in CGM initiation for their children with type 1 diabetes, there remains a significant barrier to implementation from delays in getting insurance approval. Revision of policies related to CGM coverage in youth need to be revised and systems in place to expedite approval.
MON-261 Pituitary Abscess Presenting as Pituitary Macroadenoma Causing Hypopituitarism and Acute Meningitis; A Wolf in Sheep’s Clothing
Authors: Jalil Fatima , Azim Sidra , Kantorovich Vitaly 
Published: May 2020

Abstract
Background: Pituitary abscess (PA) is a rare but life-threatening cause of suprasellar (SS) lesion and pituitary hormonal deficiencies with an incidence of 0.2% - 1.1%. Clinical Case: A 65-year woman with history of transient ischemic attacks, presented with double vision for 3 months (mon) and sudden onset, severe headache. She was diagnosed with cranial nerve (CN) VI palsy. MRI brain showed 1.7 cm SS mass suggestive of pituitary macroadenoma abutting optic chiasm. Visual field testing was unreliable due to underlying visual defects. She had progressive improvement in her diplopia. She was referred to Endocrinology for worsening fatigue. Physical exam was unremarkable. Pituitary hormonal work up showed secondary hypothyroidism with TSH 1.17 mIU/L (0.4-4.5), free T4 0.6 ng/dL (0.8-1.8); hypogonadotropic hypogonadism with FSH 12 mIU/ml (23-116.3), LH 1.7 mIU/ml (10-54.7), estradiol &lt;15 (&lt;31); elevated prolactin due to stalk affect with prolactin level of 83.3 ng/mL (3-30). She had normal IGF-1 of 154 ng/mL (41-279), ACTH 12 pg/mL (6-50), cortisol 14.1 mcg/dL (4-22) and mildly low sodium 134 mmol/L (135-146). Levothyroxine 50 mcg daily was started. The MRI brain at 2 mon and 6 mon follow up showed stable 1.8 cm peripherally enhancing SS mass. She was planned for elective pituitary adenoma resection but prior to that that was emergently admitted to ICU with high grade fever, confusion, seizures, severe hyponatremia with sodium of 122 mmol/L (135-146) and a concern for meningitis. She had a dental crown placed 3 weeks ago. MRI brain showed increase in size of the cystic component of SS mass. She was started on empiric IV antibiotics and high dose steroids. She underwent trans-sphenoidal surgery (TSS), and actually found to have a pituitary abscess. Gram stain of purulent material was positive for neutrophils. Pathology showed pituitary gland with focal infarct and surrounding acute on chronic inflammation and fibrosis. The intra-operative abscess cultures grew Cutibacterium (Proprionibacterium) acnes. She is planned to receive 6 weeks of IV antibiotics. Conclusion: We present a case of pituitary abscess presenting as a SS mass causing hypopituitarism. It was presumed pituitary macroadenoma due to the sub-acute onset and lack of progression. She developed acute deterioration in sensorium leading to concern for meningitis and PA requiring timely diagnosis and management with trans-sphenoidal resection and IV antibiotics. Definitive diagnosis of PA is usually made post-operatively. 60% of patients with PA and new onset hypopituitarism may require long term hormone replacement. References: 1. Agyei JO, Lipinski LJ, Leonardo J. Case Report of a Primary Pituitary Abscess and Systematic Literature Review of Pituitary Abscess with a Focus on Patient Outcomes. World Neurosurg. 2017 May;101:76-92
MON-700 Protective Effects of Smoking? Improved In-Hospital Mortality in Smokers Admitted for Diabetic Ketoacidosis
Authors: Nasserifar Shabnam , Ho Kam Sing 
Published: May 2020

Abstract
PURPOSE: To determine the relationship between tobacco smokers and the rate of hospital readmission within 30 days, mortality, morbidity, and health care resource utilization in patients admitted to the hospital in the United States with diabetic ketoacidosis (DKA). METHOD: A retrospective study was conducted using the AHRQ-HCUP National Inpatient Sample for the year 2014. Adults (≥ 18 years) with a principal diagnosis of DKA and a secondary diagnosis of tobacco dependence or active smokers were identified using ICD-9 codes as described in the literature (1). The primary outcome was in-hospital mortality. Secondary outcomes include readmission rate, length of hospital stay (LOS), total hospitalization costs. Propensity score (PS) using the next neighbor method without replacement with 1:1 matching was utilized to adjust for confounders (2). Independent risk factors for readmission were identified using multivariate logistic regression model (3). RESULTS: In total, 186,824 hospital admissions with a primary diagnosis of DKA were identified, of which 32.44% (47,382) had TD. In-hospital morality among the smoking cohort (0.39%, SD 0.03) was lower than the non-smoking cohort (0.32%, SD 0.04) during the first hospitalization. Similar effects were observed after propensity match - 0.33% (SD 0.18) vs 0.27% (SD 0.03). The mortality rate during next hospitalization was also lower in the smoking cohort (0.72%, SD 0.03) in comparison to their counterpart (1.16%, SD 0.01). Smokers had a higher readmission rate of 17.6% (SD 0.57) than non-smokers (9.6%, SD 0.25). The length of stay among smokers and non-smokers were similar after propensity match - 3.12 days (SD 0.03) vs 3.06 days (SD 0.09), p=0.42, respectively. Total hospital cost was also similar between the two groups, $6,898 (SD $82) vs $7,100 (SD $203), p=0.32, respectively. Based on multivariate logistic regression, female and high Charlson comorbidity index were associated with higher 30-day readmission rate; whereas private insurance and high household income were associated with reduced readmission rate. CONCLUSION: Smoking has been associated with improved survival in patients with DKA (4). Previous studies have shown that glucose concentration were significantly lower at fasting and 120 min in current smokers than non-smokers. However, the effects of cigarette smoking on glucose metabolism and insulin resistance are still disputed.
SAT-279 Crooke’s Cell Adenoma- an Aggressive Form of Cushing’s Disease
Authors: Radovanovic Natasa , Alexa Yuen , Tabatabaie Vafa 
Published: May 2020

Abstract
Introduction: Cushing’s disease is a condition of cortisol overproduction caused by an ACTH-producing tumor. Corticotroph cells surrounding an ACTH-producing tumor usually undergo Crooke’s hyaline change, where cytokeratin filaments accumulate in the cytoplasm in response to glucocorticoid excess. These changes are thought to be a mechanism of feedback inhibition and thus facilitate a suppression of ACTH. However, in a subtype of ACTH-secreting tumors known as Crooke’s cell adenomas (CCA), the ACTH-producing cells also undergo these hyaline changes. This would be expected to suppress hormone secretion but these cells are still able to release significant amounts of ACTH.
Case presentation: A 32-year-old woman presented to the hospital after an episode of syncope. On head MRI, she was found to have a 2 cm sellar mass with optic chiasm compression. Labs showed low TSH, free FT4, T3, FSH, and LH. She was also pre-diabetic with an HgbA1c of 6.2%. Her baseline cortisol of 20.6 µg/dL did not suppress after 1 mg of dexamethasone. After receiving 4 mg of dexamethasone, her cortisol suppressed to 5.2 µg/dL. She was diagnosed with hypopituitarism except for cortisol and a likely ACTH-producing pituitary macroadenoma. She completed a transsphenoidal pituitary resection and pathology revealed Crooke’s hyaline changes with immunohistochemical stains positive for ACTH. The immunostain for the proliferation marker Ki67 showed a relatively low proliferation index. Her course was complicated by diabetes insipidus. She was ultimately discharged on 20 mg hydrocortisone each morning, 10 mg hydrocortisone each afternoon, desmopressin 0.05 µg daily, and levothyroxine 125 µg daily. Two weeks later, the patient was sent to the emergency room by her endocrinologist for hyperglycemia up to 288 mg/dL. She was also found to be newly diabetic with an HgbA1c of 6.5%. A fasting morning cortisol was collected during her admission and showed a cortisol level of &lt;1.0 µg/dL, proving she was cured of Cushing’s disease. However, she will need close endocrinology follow up and MRI imaging of her pituitary for this aggressive type of pituitary adenoma.
Discussion: We have come across an interesting case of a young woman who presented for syncope and was found to have a pituitary macroadenoma with pathology consistent with CCA. This type of ACTH-producing tumor is known for aggressive patterns including high rates of recurrence with rates of up to 60% reported in literature, persistent disease after surgery, malignant transformation, and metastases. Despite presentation and symptoms similar to those of other ACTH-producing adenomas, the dangerous pattern of Crooke’s cell adenomas necessitate long-term follow-up in affected patients.