bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-279 Correlation Between Haemolitic Complement Activity (CH50) and Growth Hormone Response to Stimulation in Adult Growth Hormone Deficiency: Preliminary Data
Authors: Bruno Carmine , Basile Umberto , Vergani Edoardo , Napodano Cecilia , Piunno Gaia , Stefanile Annunziata , Gulli Francesca , Mancini Antonio 
Published: May 2020

Abstract
It is known that GH, directly or via IGF-1 activity, influences many aspects of immune response; both humoral and cellular branches are modulated, but no data are available about complement function. CH50 is a screening assay for the activation of the classical complement pathway and it is sensitive to the reduction, absence and/or inactivity of any component of the pathway. The CH50 tests the functional capability of serum complement components of the classical pathway to lyse sheep red blood cells (SRBC) pre-coated with rabbit anti-sheep red blood cell antibody (haemolysin). On the other hand, a low inflammation is present in GH deficiency (GHD) and it is related to cardiovascular risk of such situation, also in partial forms.Therefore, we performed a cohort study in a group of adult GHD patients evaluating CH50 levels to further explore the pattern of inflammatory markers in this condition.We included 17 patients with total GHD (GH peak after stimulation with GHRH+arginine &lt;9 ng/ml with BMI&lt;30 or &lt;4 ng/ml with BMI≥30 Kg/m2; n=15) or partial GHD (peak between 9 and 16 ng/ml with BMI&lt;30 Kg/m2 n=2) with mean±SEM BMI 27.7±2.6 kg/m2 and mean±SEM age 52.5±2.6 ys. The etiology of GHD, assessed by MRI, was: primary empty sella (n=7); post-surgical (n=1) pituitary adenoma (n=4); idiopathic (n=4), pineal cyst (n=1); CH50 has been assayed by turbidimetric method. Mean±SEM CH50 of entire cohort was 50.75±2.5 U/l (normal range 12.5-100 U/ml); however, a significant inverse correlation was observed between GH AUC and CH50 levels (Spearman r=-0.49; p=0.04).This datum joint to our previous observations about increased free light chains of immunoglobulins in GHD, substantiating the hypothesis of chronic low-grade inflammation affecting this condition, which in turn could negatively influence GH secretion. These data could be of interest especially in patients recognized as “idiopathic” GHD, where no pituitary morphologic alterations or anamnestic information (previous surgery, trauma or irradiation) were found. However, these data cannot be conclusive and further studies are needed to establish the causal relationships between these parameters, also in a greater cohort of patients.
MON-504 VEGFA and VEGFR2 Expression in Different Histological Types of Thyroid Nodules: Could Immunohistochemistry Have a Clinical Utility?
Authors: Bufalo Natassia Elena , Peres Karina Colombera , Teodoro Larissa , Latufi-Filho Paulo , Barreto Icleia Siqueira , Assumpção Ligia Vera Montalli , Tincani Alfio José , Maximo Valdemar , Ward Laura Sterian 
Published: May 2020

Abstract
Vascular endothelial growth factors (VEGFs) are a family of proteins involved in several elements that play an important role in the development of blood vessels. Besides acting in angiogenesis, VEGFA has important roles in chemotaxis, for macrophages and granulocytes, and vasodilation. VEGFA binds to VEGFR2, that acts on the MAPK and PI3K pathways, fundamental pathways for thyroid carcinogenesis. In order to assess the expression of VEGFA and VEGFR2, in different thyroid nodules, we used a Tissue MicroArray including 91 benign (74 females, 16 males, 49.84±12.65years old) and 125 malignant thyroid nodules (97 females, 28 males, 46.57±14.87 years old). Clinical and pathology data were obtained from 47 goiters; 43 follicular adenomas (FA) and a total of 104 papillary thyroid carcinomas (PTC), including 35 classic papillary thyroid carcinomas (CPTC), 30 follicular variant of PTC (FVPTC), 25 oxifilic variant of PTC (OVPTC), 14 tall cell papillary thyroid carcinomas (TCPTC); and 21 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 116.9±70.8 months. VEGFA protein expression did not differentiate benign from malignant thyroid nodules. However, VEGFA was more frequently expressed in the less differentiated thyroid tissues. In fact, 95.8% of the FTC had positive expression. On the contrary, the intensity of this protein expression was progressively lower according to the process of cellular dedifferentiation (Goiter: 21.4%; FA: 16.3%; PTC: 8.7% and FTC: 0.0%; x2 = 0.031). There was no difference in VEGFR2 expression between malignant and benign nodules (x2= 0.108), but this protein showed more intense expression in tissues that also presented Hürthle cells (x2 &lt;0.0001). We were not able to find any correlation, neither of VEGFA nor with VEGFR2 expression, and any other feature of aggressiveness, including invasion, metastasis, lymph node metastasis, and distant metastasis. We conclude that VEGFA and VEGFR2 expression may help identify less differentiated tumors and the analysis of a larger cohort may prove the clinical utility of these markers.
SAT-031 Linking Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) to Histone Ubiquitination Network and Acetylation During Spermiogenesis
Authors: Kavarthapu Raghuveer , Anbazhagan Rajakumar , Dufau Maria L 
Published: May 2020

Abstract
Gonadotropin Regulated Testicular Helicase (GRTH/DDX25), a testis specific RNA helicase essential for the completion of spermatogenesis. Our early studies discovered a missense mutation (R242H) of GRTH gene in 5.8 % of a Japanese population with azoospermia. This mutation in COS-1 cells showed loss of the 61 kDa cytoplasmic phospho-species with preservation of the 56Kda nuclear non-phospho form of GRTH. Mice with knock-in (KI) of the human GRTH mutation, lack the phospho-form of GRTH, are sterile and lack sperm, with spermatogenic arrest at stage 8 of round spermatids. To determine the impact of phospho-GRTH on gene expression comparative studies of germ cells transcriptome profiles from WT and KI mice were conducted using Illumina RNA sequencing. RNA-Seq analysis revealed 1614 differentially expressed genes of which 886 down-regulated and 728 genes up-regulated genes. Gene Ontology analysis revealed several genes relevant to spermatogenesis, spermatid development and differentiation significantly downregulated. KEGG analysis showed genes related to Ubiquitin mediated proteolysis, protein processing in ER, RNA transport, Glycolysis pathways are down-regulated, and genes related to Focal adhesion and ECM interaction are up-regulated. RealTime-PCR analysis confirmed dramatic reduction in mRNA expression of ubiquitination related genes Ube2j1, Ube2k, Ube2w, Rnf8, Rnf133, Rnf138 and increased expression of Ccnd2, Col1a, Lamb1, Cav1, Igf1, Itga9 mRNA’s in KI mice compared to WT. Western blot analysis revealed marked reduction in protein expression of UBE2J1, RNF8, RNF138 (ubiquitination network), MOF (histone acetyltransferase) and their modified Histone substrates (H2AUb, H2BUb), as well as H4Ac, H4K16Ac in KI mice. Immunohistochemistry analysis showed significantly reduced expression of RNF8, MOF, H4Ac and H4K16Ac in round spermatids of KI mice compared to WT. In KI mice absence of phospho-GRTH impairs RNF8 and MOF dependent ubiquitination and acetylation of histones required for histone replacement, chromatin condensation and spermatid elongation during spermiogenesis which finally results in germ cell arrest in step 8 of round spermatids. Thus, we conclude that phospho-GRTH affects the network which is critical for the replacement of histones during spermiogenesis.
SUN-545 High Prevalence of Cardiometabolic Diseases and Abdominal Aortic Calcification in Psoriasis
Authors: Ramos Sofia , Daya Sheetal , Tikly Mohammed , Crowther Nigel J , Mahyoodeen Nasrin Goolam 
Published: May 2020

Abstract
Psoriasis has been shown to increase the risk of cardiovascular disease. Studies indicate that the presence of abdominal aortic calcification (AAC) is a strong predictor of future cardiovascular events and all-cause mortality. Multi-detector computed tomography provides a reliable and accurate method for the detection of abdominal aortic calcification. The aim of this study was to investigate the prevalence of AAC in patients with psoriasis. Adult psoriasis patients (n=69) and controls (n=80) were recruited from the Dermatology and Rheumatology clinics at 3 academic hospitals in Johannesburg, South Africa. Controls were matched for gender, ethnicity and body mass index (BMI). Non-contrast abdominal CT imaging was performed on patients and controls. The images were then assessed for presence and location (supra-coeliac, supramesenteric, supra-renal, proximal infra-renal, aortic bifurcation) of AAC. Patients had a mean age and disease duration of 53.3 ± 14.5 years and 18.9 ± 13.3 years, respectively. There was a significantly higher prevalence of smoking, hypertension and type 2 diabetes in patients compared to controls (56.5% vs 25.0%, P&lt;0.005; 72.5% vs 55.0%, P&lt;0.005; 24.6% vs 3.80%, P&lt;0.0005, respectively). Furthermore, there was a significantly higher prevalence of AAC at any site in psoriasis patients (47.8% vs 22.5%, P&lt;0.005). The aortic bifurcation was the commonest site for AAC in patients and controls, and the prevalence was significantly higher in the psoriasis group (42.0% vs 21.3%, p&lt;0.005). However, multivariable logistic regression analysis demonstrated that age, smoking and the metabolic syndrome were significantly associated with AAC (P&lt;0.0001, P=0.0002, P=0.027 respectively) and attenuated the relationship between psoriasis and AAC to non-significance (P=0.376). This suggests the increased risk of aortic calcification in psoriasis is mediated by the high prevalence of cardiometabolic disease in this population. These data highlight the increased cardiovascular disease risk within subjects with psoriasis and the need for lifestyle modification to decrease risk factor burden.
OR16-01 The Expression of the Homeodomain Transcription Factor SIX3 within Kisspeptin Neurons Is Necessary for Reproduction in Mice
Authors: Lavalle Shanna N , Hernandez Jacqueline , Mellon Pamela L 
Published: May 2020

Abstract
The homeodomain transcription factor SIX3 is necessary for normal reproductive processes in mice. The loss of a single allele results in haploinsufficient phenotypes that are reflective of individuals with Kallmann Syndrome, such as hypogonadism, reduced GnRH neurons, and anosmia. Six3 heterozygous mice have reproductive impairments including an increased time to first litter, increased estrous cycle lengths in females, and fewer litters in males compared to wildtype controls. Prior studies found that deleting SIX3 specifically from GnRH neurons did not recapitulate the same phenotypes produced from a global knockout of the Six3 allele and imposed no reproductive abnormalities. This suggests that the role of SIX3 in reproduction is due to SIX3 populations outside of GnRH neurons. Using qPCR and RNA-seq, we have verified that Six3 is expressed in arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) populations of kisspeptin neurons and can regulate the kisspeptin promoter in vitro. This led us to hypothesize that SIX3 in kisspeptin neurons is required for Kiss1 regulation and maximal fertility. We selectively deleted Six3 from kisspeptin neurons by crossing a Six3-floxed mouse with a Kiss1-Cre mouse to produce Six3 flox/flox; Kiss1-Cre positive mice (cKO) and Six3 flox/flox, Kiss-Cre negative littermates (controls). In female mice, we found that the loss of SIX3 from kisspeptin neurons disrupted the estrous cycle and reduced fertility. Compared to controls, cKO mice had fewer cycles in a 16-day period (0.38 vs 1.44; p=0.004; n=8-9), and spent a greater percentage of time in diestrus (80.5 vs 61.8; p=0.002; n=8-9) and a smaller percentage of time in estrus (15.6 vs 29.2; p=0.030; n=8-9). The loss of kisspeptin-specific SIX3 also resulted in reduced fecundity, with the cKO female mice having fewer pups within 90 days (15.0 vs 34.4; p=0.048; n=5-6) compared to controls. In addition to its importance in female mice, kisspeptin-specific SIX3 also plays a role in male fertility. We found that male cKO mice had reduced motile sperm (52.2% vs 72.5%; p=0.012; n=7-9) compared to controls. We also assayed levels of Kiss1 mRNA in the male arcuate nucleus and observed decreased Kiss1 levels compared to controls (0.34 vs 1.01; p=0.042; n=3-4). These results support our hypothesis that SIX3 in kisspeptin neurons is necessary for critical reproductive processes in both females and males, including progression through the estrous cycle, fecundity, and sperm motility, potentially through Kiss1 regulation.
SAT-645 An Indication for Continuous Glucose Monitoring in Glucocorticoid-Treated Patients with Diabetes Mellitus
Authors: Sandhu Harjyot , Gilden Janice L , Wentz Lynne 
Published: May 2020

Abstract
Introduction: Continuous glucose monitoring systems (CGMS) are increasingly used to optimize management of diabetes mellitus (DM) in the outpatient setting. CGMS measure interstitial glucose concentration, which closely approximates plasma glucose after a short time lag, every 5 min for up to 72 h. CGMS provides detailed information regarding nocturnal and postprandial glycemia, whereas standard finger-stick blood glucose (BG) monitoring regimens do not. As such, CGMS has the potential to provide great insight into the glycemic effect of Glucocorticoid (GC) therapy. Case Presentation: A 76-year-old male with past medical history of DM type 2 with retinopathy and interstitial pulmonary fibrosis (IPF) requiring home oxygen therapy underwent CGMS for 2 weeks for optimization of BG control. Most recent HbA1C was 7.6%. His DM regimen included Levemir 30 units in AM and 50 units in PM, Aspart 22 units with breakfast, 18 units with lunch and 25 units with dinner, and Metformin 500mg PO BID. During this study the average BG for first 10 days on CGMS was 123-154 mg/dL with BG below 80 mg/dL about 5-28% of time. He had an acute flare of IPF during the study and prednisone 10 mg PO daily was required on the last 2 days. After starting prednisone postprandial hyperglycemia (HYPER) was noted and average BG values ranged from 185-238 mg/dL and no hypoglycemia (HYPO) was noted. Discussion: Endogenous GC excess in Cushing’s syndrome predominantly increases post-prandial BG concentration with fasting BG often in the normal range. If exogenous GCs cause a similar pattern of HYPER, current conventional strategies may inadequately treat postprandial HYPER, and use of long-acting basal insulin may precipitate nocturnal HYPO. Avoidance of HYPO is important because it has been implicated as a potential cause of increased mortality in patients receiving intensive insulin therapy. However, few studies have provided a detailed analysis of the effect of various GCs with different half-lives on BG concentration to optimize treatment of GC-induced HYPER. Our findings have important implications for clinical practice. First, prednisone-treated patients should be educated regarding the importance of checking capillary BG concentration after lunch and before and after dinner, because reliance on measurement of morning BG is likely to underestimate prednisone-induced HYPER. Second, glucose-lowering therapy should be predominantly directed at the time period between midday and midnight. Caution should be exercised with the use of long-acting basal insulin, because it may precipitate nocturnal HYPO, when the effect of prednisone wanes. Because the first glucose excursion begins on an average 3 h after prednisone administration, higher insulin doses at lunch and dinner are likely to be required. Furthermore, CGMS can be used to evaluate glycemic control in patients with DM when treated with various glucocorticoids.
SAT-073 Testicular Abnormalities in the Absence of Precocious Puberty in Mccune-Albright Syndrome
Authors: Verma Arushi , Di Blasi Carolina Cecilia 
Published: May 2020

Abstract
Background: Mc-Cune Albright Syndrome (MAS) is a rare disorder characterized by skeletal lesions, skin hyperpigmentation and hyperfunctioning endocrinopathies. Gonadotropin-independent precocious puberty is the most common endocrinopathy, known to be more common in females than males, but little is known about male gonadal pathology in MAS.
Clinical case: 3-year-old boy presented with worsening unilateral limp and was noted to have a pathologic femoral fracture. Bone scan demonstrated extensive fibrous dysplasia in the long bones and skull base. He had a large café au lait spot on the back. He was diagnosed with MAS on clinical criteria.
At 4 years of age, initial exam was normal without signs of precocious puberty. Linear growth followed the 70th percentile, on track for his genetic background (mid parental height 70th percentile). Initial hormonal work up showed normal thyroid function, prolactin, growth factors and pre-pubertal gonadotropins and testosterone.
At 6 years of age, he started to demonstrate bilateral testicular enlargement of 4-6 mL with pubic hair Tanner stage I. Bone age was concordant with chronologic age. Gonadotropins and testosterone level were pre-pubertal. Testicular ultrasound showed bilateral enlargement with punctuate densities without evidence of hydrocele or mass.
By 8 years of age, he had further testicular enlargement to 8 mL bilaterally, normal penile length 5.5 cm (6.2 ± 1.0) and no pubic hair. Biochemical evaluation showed normal thyroid function and pre-pubertal gonadotropins and testosterone. Repeat testicular ultrasound showed heterogeneous echotexture representing microlithiasis, without a focal mass.
Conclusion: Macroorchidism can be present in the absence of gonadotropin independent precocious puberty in MAS. Testicular ultrasound evaluation is important, as hyper-hypoechoic lesions, bilateral microlithiasis, focal calcifications, are the most common testicular abnormality in males with MAS.
Microlithiasis, due to calcium deposits within the seminiferous tubules, have been described often in this condition, and should be considered a marker of male MAS. The natural history of male fertility and testicular cancer risk in the context of microlithiasis and testicular calcifications is unknown. Close observation and testicular imaging at baseline and after age 5, to characterize subclinical involvement, are an appropriate course to follow.
MON-084 Hyperosmolar Hyperglycemic State as Initial Presentation of Type 1 Diabetes in Children
Authors: D’Ambrosio Fabiola , Marranzini-Rodriguez Isabella , Castaneda Roxana Aguirre , Boucher-Berry Claudia 
Published: May 2020

Abstract
INTRODUCTION: We present 2 pediatric patients with Hyperosmolar Hyperglycemic State (HHS) at diabetes onset.
CASE 1:
3 year old African American female presented to the pediatrician office with a 5 day history of polydipsia, polyuria and emesis. POCT glucose read high and patient was transferred to the PICU. Laboratory studies were significant for serum glucose of 1032 mg/dl, Na 128 mMOL/L (corrected 142mMOL/L), VBG showed pH 7.36, HCO3 20 mMOL/L, Serum osm 331 mOsm/Kg. Patient received a 20ml/kg bolus of 0.9%NaCl, followed by 2 times maintenance IV fluids and glargine 2 units. Glucose dropped from 418 to 122 mg/dl in 3 hours. Due to this Dextrose was added and IVF rate was decreased.
CASE 2:
8 year old African American obese male was admitted to the PICU for management of new onset diabetes. He presented with 3 days of flu-like symptoms and worsening drowsiness. Patient had increased consumption of large quantities of sugary beverages due to increased thirst. Laboratory workup: serum glucose of 2309 mg/dl, Na 133 mMOL/L (corrected 168 mMOL/L), pH 7.13, HCO3 10 mMOL/L. Patient was given 30 cc/kg NS bolus followed by an insulin drip of 0.1 u/kg/hour. Repeat studies 3 hours later showed a serum glucose of 1,414 mg/dl, Na 152 mMol/L (corrected 184 mMOL/L), pH 7.19, HCO3 17 mMOL/L, and serum osmolality of 408 mOsm/Kg. IVF were adjusted to correct the water deficit and insulin drip was decreased to 0.05u/kg/hour.
DISCUSSION: HHS continues to be a challenging diagnosis due to its low frequency compared with Diabetic Ketoacidosis especially when presenting at a very young age. Most practitioners will mistake the presentation for DKA and start an insulin drip. The early use of insulin is not necessary in the setting of HHS due to the risk of complications. A fast drop in glucose decreases the osmotic pressure and compromises the circulatory status with a higher chance of thromboembolism. In mixed HHS and DKA, the management aligns more with the DKA management but the amount of fluids needed is higher and insulin infusion may cause fast drop of glucose with potential decrease of intravascular volume as in our second patient. It is imperative that the diagnosis of HHS is made early so that the appropriate treatment can be instituted.
CONCLUSION: Appropriate fluid administration and delay in insulin administration are key in the management of HHS. The awareness of this possible presentation and the early recognition and appropriate fluid management are needed to improve outcomes.
REFERENCE:
Zeitler, Phil, et al. “Hyperglycemic Hyperosmolar Syndrome in Children: Pathophysiological Considerations and Suggested Guidelines for Treatment.” The Journal of Pediatrics, vol. 158, no. 1, 2011, doi:10.1016/j.jpeds.2010.09.048