bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-553 Use of Optimal Cutting Temperature Compound (OCT)-Embedded Adrenal Tumor Tissue for Intratumoral Steroid Hormone Profiling
Authors: Garber Scott R 
Published: May 2020

Abstract
Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 5-8% of all hypertension. PA is most commonly attributed to an aldosterone-producing adenoma (APA) or to bilateral hyperaldosteronism (BHA). Mutations in the inward-rectifying K+ channel (mKCNJ5), which increase autonomous aldosterone production, are most frequently detected in APAs. APAs with mKCNJ5 display aberrant expression of aldosterone synthase (CYP11B2) and 17α-hydroxylase (CYP17A1), which are involved in aldosterone and cortisol synthesis, respectively. Co-expression of these enzymes results in the production of a set of “hybrid” steroids, which have been proposed as serum biomarkers. The relative production of hybrid steroids in adrenal tumors vs. adjacent normal adrenal (NA) tissue has not been investigated. Objectives: To determine the utility of OCT-embedded adrenal tumor tissue for steroid profiling. To use immunohistochemistry (IHC)-guided OCT tumor capture for intratumoral hybrid steroid profiling in mKCNJ5 APA and NA tissue. Methods: OCT-embedded adrenal tissue from 9 patients (8 women, Age 45.9 ± 3.3 years) with APAs harboring known KCNJ5 mutations were used for the study. Where available OCT-embedded normal adrenal (NA) tissue adjacent to APAs were used as controls (n=4). IHC was performed for CYP11B2 and CYP17A1 on OCT tissue allowing guided APA capture from serial sections. Steroids were extracted from APA and adjacent NA tissue, and quantified by liquid chromatography/tandem mass spectrometry. Steroids measured were normalized to the protein content of the extracted tissue. Results: Compared to NA, APA tissue demonstrated 23-, 5.6- and 6.4-fold higher levels of aldosterone, 11-deoxycorticosterone, and 18-hydroxycorticosterone, respectively (P&lt;0.05). In addition, the “hybrid” steroid products, 18-oxocortisol and 18-hydroxycortisol, were significantly elevated in APA vs. NA (P&lt;0.01). Conversely, the adrenal androgens dehydroepiandrosterone and 11-hydroxyandrostenedione were lower in APA as compared with NA (P&lt;0.05). All mKCNJ5 APAs were also found to co-express CYP11B2 and CYP17A1. Conclusion: IHC-guided mKCNJ5 APA capture and steroid extraction identified a distinct intratumoral hybrid steroid signature that associated with co-expression of CYP11B2 and CYP17A1.These findings also demonstrate that OCT-embedded tissue can be used to accurately define intra-tissue steroid profiles, which will have application for steroid-producing and steroid-responsive tumors.
MON-326 Non Functioning Pituitary Adenomas (NFPA): Sex Related Differences in Presentation, Clinical Features and Outcomes
Authors: Rosmino Josefina , Tkatch Julieta , Guitelman Mirtha Adriana 
Published: May 2020

Abstract
INTRODUCTION: NFPA are characterized as tumors without a typical hormonal hypersecretion syndrome. They are frequently diagnosed in the sixth decade, by visual field defects, hypopituitarism or incidentally. PATIENTS AND METHODS: retrospective and observational study that included 103 patients with NFPA (60 females) who were seen between 1999 and 2019 in our hospital. We compared and analyzed patients characteristics by sex: reason for consultation, hormonal status at diagnosis, invasiveness of the tumor through MRI, treatments and outcomeRESULTS: out of 103 patients, 58,2% were women (W). Men (M) were significantly older than women (56 vs. 45 yold. p=0,002). The presence of a macroadenoma was similar in both sexes (93%W vs. 94,7% M), however tumor invasiveness was more frequent in men (50% vs. 24,6%). Most men consulted for incidental finding (47,4% vs. 29,8%); most women consulted for symptoms related to the tumor(70% vs 52%): hypogonadism 31,6% W, 13% M; galactorrhea 17% W; visual field defects 21,7% W, 23,7%M, pituitary apoplexy 11,6% M. At baseline hormonal assessment hyperprolactinemia was more frequent (50,9% vs 42%) and higher in women (mean PRL levels 75 ng/ml vs. 37 ng/ml). Hypogonadism was more frequent in men (54% vs 42%) as well as hypopituitarism (15% vs. 10,5%). Surgery was the most used therapy in both sexes (69% M vs. 73%W) but males required more frequently second surgery and radiotherapy than females (15% vs. 5% and 10% vs. 5% respectively). Gonadotropin secreting adenoma was diagnosed in 62% of men and 37,5% by tumor immunohistochemistry, in the 45% of women who presented negative immunostaining the presence of a gonadotrophic lineage is not ruled out, median Ki-67 labeling was low in both sexes (2%). After surgery 66% of men and 37% of women showed tumor remnant &gt; 1cm (p=0,001), tumor regrowth was seen in 38,4% men and 10,4% women (p=0,03). Hypogonadism was greater in men than in women (56% vs 39%). Ninety two percent of men and 60,9% of women developed some degree of pituitary deficiency after surgery (P&lt;0,001). Men showed a higher degree of complete hypopituitarism compared to women (pretreatment 15% vs 10,5%, post treatment 32% vs 13%). CONCLUSION: NFPA in men are usually diagnosed incidentally at an older age, are more invasive at presentation with a higher incidence of pituitary dysfunction. Moreover, they presented with greater rate of tumor regrowth and hypopituitarism after surgery. NFPA in women are diagnosed earlier due to endocrine symptoms, had lower degree of invasiveness with better outcomes after treatment. Sex related differences in NFPA may be associated with the delay in diagnosis, although a more aggressive biology cannot be discarded.
SAT-080 SLC29A3 Pathogenic Variant as a Causal for Dysosteosclerosis, a Poor Osteoclast Form of Osteopetrosis
Authors: Seiltgens Cristian , Rauch Frank , Bardai Ghalib 
Published: May 2020

Abstract
Background: Dysosteosclerosis (DSS) is a rare autosomal recessive form of osteopetrosis characterized by metaphyseal osteosclerosis and platyspondyly. At the histopathological level, a paucity of osteoclasts has been described when the disease presents genetic heterogeneity. SLC29A3 encodes a nucleoside transporter, that colocalizes intracellularly on the lysosomal membrane, is essential for lysosomal function and which is expressed in osteoclasts. Clinical case: We present a female patient from a nonconsanguineous camerunense family with DSS. Her first fracture at the age of 1 year occurred in the proximal right humerus following a very mild trauma. Subsequently she was referred to our clinic at the age of 1.8 months. At the last evaluation in our clinic at the age of 5.6 years she had suffered 5 femur fractures, 2 humerus fractures and a tibia/fibula fracture. XRays shown cortical thickening and widening of the diaphysis of the long bones, cranial base sclerosis, broad ribs with sclerosis and platyspondyly. Bone marrow biopsies and bone biopsy were not performed. The subject did not have any neurological symptoms, dental anomalies or present any dermatological issues. Dual-energy X-ray absorptiometry of the individual showed a lumbar spine BMD Z-score of +8 at 20 months of age, +7.1 at 3 years 5 months, +6.4 at 4 years 6 months and +5.1 at 5 years 6 months of age. TRACP 5 B 4.7 U/L is low in concordance with an osteoclast poor osteopetrosis, and the RANKL&gt;&gt;2.1 ipMol/L is high. On the other hand, CTX 1.298 ng/mL is normal. We identified and confirmed the homozygous pathogenic variant p.Arg386Gln in SLC29A3 using whole exome sequencing and sanger capillary electrophoresis.Conclusion: In summary, we show that a homozygous change in exon 6 of SCL29A3 (NM_00074; c.1157G&gt;A; pArg386Gln) results in a phenotype of Dysosteosclerosis, adding a case to the small group of patients were pathogenic variants in this gene have been described causing sclerosing bone dysplasias with hallmarks of dysosteosclerosis. Interestingly, the other DSS cases and H syndrome cases confirms the clinical heterogeneity of disorders caused by mutations in SLC29A3 and the lack of a clear genotype-phenotype correlation. Phenotypically is also interesting to show that in our patient the bone mineral density has been decreasing over the time, with the concording increasing of TRAB5b. More mutations and functional investigations are needed to get a clearer picture for SCLC29A3 and how is involve in the process of osteoclast differentiation and activity.
SAT-036 Redefining Eunuchoid Body Proportions in Adults
Authors: Singh Santosh Kumar 
Published: May 2020

Abstract
Different population groups have different normal adult body proportions.A retrospective study was done on 100 males with age range of 20 to 58 years.Thirty (30%)males had arm span greater than height and upper segment and lower segment ratio(US/LS) below 0.9 which was a proposed criterion for eunuchoid body proportion by Winters.1Moreover,sixty-three(63%) males had arm span greater than 5 cm which was greater than the 2 cm criterion of Santen.2 Only three(3%) males had arm span 1 SD above mean(172.55 ± 12.01 cm) and US/LS 1 SD below mean(0.91 ± 0.04 cm). Hence,eunuchoid body proportions in adults should be defined in terms of SD from mean for the particular sex and race.The body proportion could be due to delayed puberty in Indians compared to the Western population.
References
1.Winters SJ:Clinical Disorders of the Testis.In Leslie J Degroot eds.Endocrinology.3rded. W. B. Saunders Company 1995;2377-2403.
2.Santen RJ:The Testis.In P.Felig et.al. eds.Endocrinology and Metabolism.2nd ed.McGraw Hill,1981,821-905.
MON-001 Peripartum Sertraline (Zoloft®) Increases Pup Mortality Immediately Postpartum
Authors: Sheftel Celeste , Sartori Luma C , Manuel Robbie , Fricke Hannah , Bell Autumn , Mulvenna Elizabeth , Hernandez Laura L 
Published: May 2020

Abstract
Peripartum and postpartum depression can be detrimental to both the mother and the developing child. Use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is common during the peripartal period and SSRIs have been the leading prescribed antidepressant to treat maternal depression. One of the most commonly prescribed SSRIs is sertraline (Zoloft®) because of the limited fetal teratogenic effects observed, unlike maternal paroxetine (Paxil®) usage which can manifest in fetal cardiovascular defects. Fluoxetine (Prozac®), like sertraline, has previously been shown to have limited teratogenic effects, however, we have shown treatment with fluoxetine for the entire period of pregnancy and lactation in mice compromises pup bones at weaning resulting in decreased long bone length and head circumference. Furthermore, maternal fluoxetine usage results in a sustained reduction in maternal bone mineral density post weaning, which may lead to long-term osteopenia, putting the mother at risk for bone-related disorders later in life. We hypothesized sertraline, like fluoxetine, will compromise maternal bone postpartum and fetal bone development at weaning. Treatment with sertraline in C57BL/6 dams throughout pregnancy and lactation reduced litter size (5.4 pups/dam) and increased pup mortality during the first 24 hours postpartum (20% dead pups/litter) compared to controls (6.8 pups/dam, 5% dead pups/litter, respectively; P &lt; 0.018). Maternal calcium transporters (Orai1 and Serca2) were downregulated in the mammary gland in sertraline-treated dams on day 21 of lactation (P &lt; 0.0032). Together, our data suggests in utero pharmacological exposure to sertraline may induce a failure to thrive in the pups and alters calcium metabolism in the dam. SSRI exposure during pregnancy and lactation may adversely affect the developing neonate(s) as well as have lasting impacts on the mother.
SUN-235 Deficient Fear Extinction in PRKAR1A-Defective Mice
Authors: Keil Margaret , Paradiso Enrica , Keil Rita S , Ugolini Maddalena , Harris Evan , Wu T John , Stratakis Constantine A 
Published: May 2020

Abstract
Background: The role of the cAMP/PKA signaling in molecular pathways involved in fear memory is well established: PKA is required for fear memory formation and is a constraint for fear extinction. Previously we reported that a Prkar1a heterozygote (HZ) mouse that was developed in our lab to investigate Carney complex (CNC), the disease caused by PRKAR1A mutations, showed brain region-specific increased PKA activity that was associated with anxiety-like behavioral phenotype and threat bias (Keil, 2010, 2013). We hypothesized that Prkar1a+/- (HZ) mice would have deficits in fear extinction behavior. Brain derived neurotrophic factor (BDNF) has a critical role in formation of fear memory and its transcription is regulated by PKA/CREB. A mouse model with down regulation of PKA provides an opportunity for the first time to investigate the effect of altered PKA signaling on fear conditioning and extinction.
Method: Fear conditioning, fear extinction learning, and fear extinction recall were tested in adult male HZ and wild-type (WT) mice as follows: fear conditioning training followed 24hr later by extinction training (new context), then 24hr later by extinction recall training. Percentage of time freezing was used to assess conditioned fear response. We measured BDNF gene expression in brain regions after completion of extinction recall training.
Results: As expected, fear conditioning (learning) behavior was similar in HZ and WT mice. However, HZ mice showed a significant deficit in the early phase of fear extinction learning compared to WT. There was no difference in extinction recall between genotypes. Alterations in BDNF gene expression in the prefrontal cortex and amygdala was associated with deficit in fear extinction.
Conclusion: Mice with a downregulation of Prkar1a gene demonstrate intact fear conditioning but impaired fear extinction learning, consistent with prior studies that report that PKA inhibition is necessary to facilitate extinction learning. Prkar1a+/- mice provide a valuable model to investigate impaired fear extinction to identify mechanisms for therapeutic targets for anxiety and trauma-related disorders.
OR06-05 Inadequate High Mitochondrial ATP-Synthesis Explains “Non-Fatty-Liver” in Patients with Acromegaly
Authors: Fellinger Paul , Wolf Peter , Pfleger Lorenz , Martin Krssak , Kristaps Klavins , Stefan Wolfsberger , Alexander Micko , Patricia Carey , Bettina Gürtl , Vila Greisa , Raber Wolfgang , Clemens Fürnsinn , Scherer Thomas , Siegfried Trattnig , Kautzky-Willer Alexandra , Krebs Michael , Yvonne Winhofer 
Published: May 2020

Abstract
Background
Patients with active acromegaly exhibit low hepatocellular lipid content (HCL) despite pronounced insulin resistance. This contrasts the strong association of insulin resistance with non-alcoholic fatty liver disease in the general population. Acromegaly may therefore help to elucidate antisteatotic pathways. Since low HCL in acromegaly might be caused by changes in oxidative substrate metabolism and interorgan crosstalk we investigated mitochondrial activity and plasma metabolomics as well as lipidomics in active acromegaly.
Approach & Results
Patients In this cross-sectional study, 15 patients with active acromegaly (ACRO) and 17 healthy controls (CON) matched for age, BMI, gender and body composition were included. All participants were invited to undergo 31P/1H-7T-MR-spectroscopy of the liver and skeletal muscle, as well as plasma metabolomic profiling and an oral glucose tolerance test.
In comparison to CON, ACRO were insulin resistant, and showed significant lower HCL but their hepatic ATP-synthesis rate adjusted to HCL was significantly increased (h_kATP:0.19[0.14;0.24]vs0.28[0.22;0.34]s-1);p=0.024). Furthermore, the HCL-adjusted ratio of unsaturated to saturated intracellular fatty acids was decreased in ACRO (8.4%vs25.5% of HCL,p&lt;0.04). In skeletal muscle, intramyocellular lipids and ATP-synthesis rate were significantly decreased in ACRO. Plasma lipids and lipidomics did not differ between ACRO and CON, but decreased levels of carnitine species were observed in ACRO.
Conclusions
The dissociation of hepatic lipid content and peripheral insulin resistance in acromegaly is associated with high mitochondrial activity as indicated by liver specific upregulation of the ATP-synthesis rate. This is paralleled by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a change in circulating carnitine species, also reflecting an increased mitochondrial activity. Our findings hint at potential direct effects of growth hormone excess on hepatic lipid and energy metabolism.
MON-109 Modulator of Gut Barrier, Zonulin Was Associated with Waist to Height Ratio in Adolescents
Authors: Kim Ki Eun , Kim Ok-Hyang , Han Sol , Sheen Youn-Ho , Kim Soo-Yeon 
Published: May 2020

Abstract
Background: Zonulin is the endogenous protein known to control the permeability of intestinal tight junction reversibly. Zonulin is actively engaged in intestinal innate immunity and is over-expressed in autoimmune diseases where tight junction of intestine plays a pivotal role, such as celiac disease, malabsorption disorder, and type 1 diabetes. Waist-Height ratio was well known as one of indices of obesity and also Waist-Hip ratio was known of abdominal obesity. We investigated that the associations among Waist-Height, Waist-Height ratio, and the level of Zonulin by assessing obesity-related biomarkers, such as liver enzymes, lipid profiles, and insulin resistance, in a population of adolescents.
Methods: The study included 198 adolescents aged 12-18 years; 92 were overweight/obese and 106 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), BMI z-score, Waist-Height, Waist-Hip ratio, blood pressure, liver enzyme levels, lipid profiles, and insulin sensitivity. Serum Zonulin levels were measured using an enzyme-linked immunosorbent assay.
Results: The mean age of the participants was 15.2±2.5 years. Circulating serum Zonulin levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (P=0.042). Zonulin levels were significantly and positively associated with BMI, BMI z-score, alanine aminotransferase levels, triglyceride, fasting insulin, and insulin resistance as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (all P&lt;0.05). In multivariate linear regression analysis, alanine aminotransferase (P&lt;0.0001), triglyceride (P&lt;0.0001), and HOMA-IR (P=0.001) contributed independently to circulating Zonulin levels after controlling for the effect of BMI z-score. Zonulin levels were more strongly associated with Waist-Hip ratio rather than Waist-Height ratio.
Conclusions: Zonulin was associated with indices of obesity. Waist-Hip ratio was more strongly associated with levels of Zonulin. The positive correlation between these parameters suggests putative pathophysiological mechanism linking Zonulin to metabolic dysfunction in adolescents.
SAT-717 Region-Specific Effects of the Exposome on Brain Monoamine Levels in Female Rats
Authors: Kaimal Amrita , Hooversmith Jessica , Mansi Maryam H Al , Holmes Philip V , MohanKumar Sheba M J , MohanKumar Puliyur S 
Published: May 2020

Abstract
Prenatal programming with endocrine disrupting chemicals (EDCs), in particular the ubiquitous plasticizers bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP), can induce long-lasting behavioral changes in rats. Additionally, changes in estrogen are correlated with the development of mood disorders in women; however, the underlying neurobiological mechanisms are unclear. This study was conducted to determine the cumulative effects of prenatal exposure to EDCs followed by chronic estradiol treatment in adult female rats on monoamine levels in the prefrontal cortex (PFC) and hippocampus (HC). Dams were orally administered saline (control; 10 µL/kg), BPA (B; 5 µg/kg), DEHP (D; 7.5 mg/kg) or a combination of BPA+DEHP (B+D) during days 6 through 21 of pregnancy. Adult female offspring were sham-implanted or implanted with pellets that release 17β-estradiol (E2) for 90 days (20 ng/day; Innovative Research America). The offspring then underwent a battery of behavioral tests at the end of treatment. Brains collected from the offspring were sectioned and the PFC and HC were microdissected and analyzed for levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), using High-Performance Liquid Chromatography (HPLC). Significant reductions in monoamine levels were observed in the PFC while NE and 5-HT levels were markedly reduced in the HC after prenatal exposure to D or BD. BPA’s effects on monoamines were comparatively modest. E2 exposure increased DA but decreased 5-HT levels in the PFC of control animals. Prenatal exposure to EDCs made the offspring non-responsive to E2. The marked reduction in monoamine levels could have implications for learning and memory.
OR13-01 Comparison of Vitamin D Metabolism in Deficient and Sufficient States
Authors: Zhukov Artem , Povaliaeva Alexandra , Pigarova Ekaterina , Dzeranova Larisa , Bogdanov Victor , Ioutsi Vitaliy , Rozhinskaya Liudmila 
Published: May 2020

Abstract
Objective: to study the differences in calcium-phosphorus and vitamin D metabolism in healthy individuals with deficient and sufficient baseline state of vitamin D. Materials and methods: The study included 16 young conditionally healthy individuals, divided into two equal groups: with levels of 25(OH)D below and above 30 ng/ml determined by the immunochemiluminescent method (Group A and Group B respectively; DEQAS certified). All participants were evaluated for the biochemical parameters of blood and urine, characterizing calcium-phosphorus metabolism, PTH by commercial methods, and vitamin D metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) by HPLC/MS-MS before oral intake of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: At baseline, the level of vitamin D metabolite 25(OH)D2 in Group B was lower with no significant differences in other studied parameters. In group A, strong positive correlations were observed between levels 25(OH)D3 and 3-epi-25(OH)D3, 24,25(OH)2D3, while in group B there were no such associations. After taking a loading dose of cholecalciferol, the groups showed generally similar changes in the studied vitamin D metabolites: a statistically significant increase in 25(OH)D3, 3-epi-25(OH)D3, a decrease in 25(OH)D2, and a ratio of 24,25(OH)2D3 to 25(OH)D3. However, the level of 24,25(OH)2D3 did not change in group B, with a significant increase in group A. The medians of the studied biochemical parameters in blood/urine, as well as PTH, remained unchanged in both groups. Conclusion: In patients with inadequate baseline levels of 25(OH)D, after a loading dose of cholecalciferol, there is a tendency to formation of more inactive forms of vitamin D. These deviations in the metabolism of vitamin D need to be clarified, since they can potentially affect the effectiveness of cholecalciferol therapy.