bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-245 A Rare Case of Clival Primary Diffuse Large B-Cell Lymphoma Presenting with Panhypopituitarism and Unmasked Diabetes Insipidus
Authors: Sonnabend Hajerah , Go Muriel Tania L , Iyengar Ravi M
Published: May 2020

Background: Central adrenal insufficiency (AI) is known to conceal diabetes insipidus (DI) by impairing free water clearance from the renal system and inhibiting polyuria, which is later unmasked by the initiation of glucocorticoids. The instances of masked DI in the literature are confined to case reports - the actual incidence is unclear. There have been no documented cases of masked DI secondary to a clival tumor, which remains a rare cause of hypopituitarism. Here we discuss a case of primary diffuse large B-cell lymphoma (DLBCL) of the clivus presenting with panhypopituitarism and the development of DI upon glucocorticoid initiation.

Clinical Case: A 60-year-old man with DLBCL initially presented to an outside institution with headache, diplopia, and right eye ptosis. Brain MRI showed enhancement of the clivus without obvious pituitary gland involvement. He underwent biopsy with partial resection of the tumor and pathology confirmed DLBCL. His course was complicated by persistent fevers. Extensive work-up was unrevealing and he was transferred to our institution for further management. On admission, infectious work-up was positive for C. Difficile. He later developed septic shock requiring vasopressors and broad-spectrum antibiotics. Despite prolonged antibiotics, he remained hypotensive. Due to proximity of the clivus and sella, there was concern for pituitary involvement. A random cortisol was 9.1 [3.7-19.4 ug/dL], subsequent 250ug cosyntropin stimulation test yielded 13.1 and 14.9 at 30- and 60-minutes, respectively. Given inadequate stimulation and persistent hypotension in this critically ill patient, he was then started on stress dose hydrocortisone (HC) with prompt resolution of hypotension. Further work-up of the pituitary axes was consistent with anterior hypopituitarism: ACTH 5 [6-50 pg/mL], TSH 0.336 [0.350-4.940 uIU/mL], free T4 0.5 [0.7-1.5 ng/dL], FSH 0.3/LH 0.1 [1-10 mIU/mL], IGF-1 <16 [41-279 ng/mL], prolactin <1 [3-16 ng/mL]. On day two of HC stress dosing, he developed hypernatremia and polyuria. Urine studies were consistent with DI and desmopressin was started with subsequent improvement.

Conclusion:This is the first documented case of DLBCL of the clivus leading to panhypopituitarism. For tumors in close proximity to the pituitary, there should be a low threshold for pituitary axes evaluation. In addition, masked DI from central AI remains rare and requires close attention by the Endocrinologist following initiation of glucocorticoids.
SAT-473 Thyroid Dysfunction in a Patient with Malignant Melanoma Treated with Immune Checkpoint Blockade
Authors: Gupta Shaveta , Yin Ngwe
Published: May 2020

Thyroid Dysfunction in a Patient with Malignant Melanoma Treated with Immune Checkpoint Blockade

Background: Thyroid dysfunction is a known immune-related adverse event associated with immune checkpoint inhibitor therapy.

Clinical Case: 48 year old female, newly diagnosed with metastatic melanoma started on combination immune checkpoint inhibitor therapy with Ipilimumab and Nivolumab. Her baseline thyroid function tests were normal. 6 weeks after the first cycle, she was found to have TSH of 0.010IU/ml with FT4 3.33IU/ml. Patient was started on Prednisone for 2 weeks and beta-blocker for symptom control by oncology team and referred to endocrine clinic for further evaluation. She was diagnosed with thyroiditis. TSI and thyroid uptake scan were not checked as there was no clinical suspicion for Graves disease in the absence of ophthalmopathy and thyroid enlargement. Serial TFTs were obtained which showed improvement. However, 4 weeks later, patient developed overt hypothyroidism (TSH 11.800IU/ml, FT4 0.68IU/ml) for which therapy with levothyroxine was started.

Conclusion: Our case emphasizes the importance of close monitoring of patients receiving Immune Checkpoint Inhibitor Therapy for prompt diagnosis and management of the thyroid disorders to prevent complications such as thyroid storm or myxedema coma. Per the ASCO guidelines, Brahmer et al recommends monitoring TFTs every 4 to 6 weeks from the start of the therapy and every 2-3 weeks after the diagnosis to detect conversion of thyroiditis and hyperthyroidism to hypothyroidism. In the combination therapy, the median time to onset of hyperthyroidism and hypothyroidism after first treatment was 21 and 63 days and transition time from hyperthyroidism to hypothyroidism was 42 days.

Reference: (1) Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy Lee et al

(2) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

Julie R. Brahmer et al
SUN-667 Hyperinsulinemia Suppresses Hepatic Autophagy at Late Sepsis in an mTOR-Dependent Transcriptional Regulation
Authors: Hsu Chin , Wang Li-Fang
Published: May 2020

Autophagy transiently occurs in the liver at early stage, while autophagy suppression associated with liver failure occurs at late stage in a CLP (cecal ligation and puncture) model of sepsis. However, the factors that cause autophagy suppression at late sepsis remain unknown. Hyperinsulinemia is observed in early sepsis, and insulin inhibits autophagy via mTOR, which regulates TFEB/ZKSCAN3 nuclear translocation and the transcription of autophagy-related genes (LC3, p62, WIPI2, ATG9 etc.). Thus, we used CLP mouse model of sepsis to test the hypothesis that early hyperinsulinemia suppresses late hepatic autophagy via the mTOR-dependent transcriptional regulation of autophagy-related genes. The results showed that hyperinsulinemia occurs 3 h after CLP (CLP3h) and is followed by mTOR phosphorylation and autophagy suppression at the late stage (CLP9~15h) of sepsis. The administration of HNMPA, an insulin receptor antagonist, decreases mTOR/ULK-1 (unc-51 like autophagy activating kinase 1) phosphorylation and relieves autophagy suppression in late sepsis. Encapsulated rapamycin, which blocks hepatic mTOR/ULK-1 signaling downstream of insulin, enhances the nuclear translocation of TFEB in early sepsis, increases the protein expression of autophagy-related genes (LC3 and p62) and relieves autophagy suppression in late sepsis. Moreover, rapamycin rescues hepatic dysfunction and increases the survival rate after CLP. These results suggest that early hyperinsulinemia suppresses hepatic autophagy in late sepsis in an mTOR-dependent manner.

Nothing to Disclose: LW, PC, YL, CH
SAT-204 ACTH-Producing Pheochromocytoma, a Challenging Disease to Diagnose and Manage
Authors: Ferrari Aldo De , Pywell Cameron , Bahl Deepti
Published: May 2020

Background: ACTH-producing pheochromocytomas (APP) are a rare cause of ectopic Cushing’s syndrome (CS), representing <6% of these cases. No guidelines exist on the management of these tumors.

Clinical case: A 41-year-old woman presented to the ED with a 6-month history of newly-diagnosed T2DM and difficult-to-control hypertension. Three weeks prior to admission she developed fatigue, dyspnea on exertion, and generalized weakness particularly severe in the lower extremities (LE) limiting her ability to ambulate. She denied headaches, palpitations and diaphoresis. Initial vital signs included HR 111 beats/min and BP 217/112 mmHg. On physical exam she had classic findings of CS with severe LE weakness. Laboratory testing was consistent with ACTH-dependent CS (ACTH 463 pg/mL [0-45], cortisol 70.8 mcg/dL [3-23], potassium 2.7 mMol/L [3.1-5.1]). She failed both the low dose (1 mg) and high dose (8 mg) dexamethasone suppression tests. MRI of the pituitary gland ruled out a pituitary lesion. IPSS was not deemed necessary by Neurosurgery. CT abdomen showed a 4.2 cm right adrenal lesion and bilateral adrenal hyperplasia. This prompted workup for pheochromocytoma that revealed elevated plasma metanephrines (4.1 nMol/L, [<0.5]) and 24hr urine metanephrines (5329 mcg/day, [182-739]). A diagnosis of APP was entertained. Doxazosin 1 mg BID was added to her other antihypertensives with improvement in blood pressure. Ketoconazole 200 mg TID was started as a bridge for surgery. Patient underwent right unilateral adrenalectomy one month after initial presentation. ACTH and cortisol levels before surgery were 534 pg/mL and 87 mcg/dL, respectively, suggesting that ketoconazole was not effective. Both ACTH and cortisol levels decreased to 26 pg/mL and 14.4 mcg/dL, respectively, immediately after surgery. There was prompt subjective symptomatic improvement, including mild recovery of LE strength. Her blood pressure normalized and only spironolactone was continued. She was started on a prednisone taper. Pathology revealed a 4.2 pheochromocytoma and diffuse adrenocortical hyperplasia. Tumor cells stained positive for ACTH on immunohistochemistry. On follow up visit 2 months after surgery patient was feeling well and ambulating without difficulty. Labs were remarkable for normal plasma fractionated metanephrines, and A1c 5.1% on metformin alone (down from 4 medications on initial presentation).

Conclusion: Diagnosis and management of APP can be challenging. Alpha-blockers should be started promptly. Definitive treatment with unilateral adrenalectomy is curative and has been recommended as the preferred approach.1 Ketoconazole may be used as bridge therapy for surgery, though some studies suggest its efficacy might be lower in ectopic CS.2 Response to other pharmacologic agents is largely unknown.

References:

1. Surgery (1995) 118: 988-94

2. Clinical Endocrinology (1991) 34: 63-70
SUN-039 Estradiol Dose and Concentrations in Transfeminine Individuals
Authors: Nolan Brendan J , Brownhill Adam , Bretherton Ingrid , Wong Peggy , Fox Susan , Locke Peter , Russell Nicholas D , Grossmann Mathis , Zajac Jeffrey D , Cheung Ada S
Published: May 2020

Background: Feminizing hormone therapy with estradiol is used to align an individual’s physical characteristics with their gender identity. Australian expert consensus guidelines (1) recommend targeting estradiol concentrations of 250-600 pmol/L (68-163 pg/mL) based on local cross-sectional data (2). We aimed to establish the proportion of individuals achieving estradiol concentrations in consensus guidelines.

Methods: A retrospective cross-sectional analysis was performed of transfeminine individuals attending a primary or secondary care clinic in Melbourne, Australia who were prescribed oral estradiol valerate for at least 6 months and had estradiol dose and concentration available. Estradiol concentration was measured by immunoassay. Outcomes were (1) proportion of individuals achieving target estradiol concentrations and (2) influence of estradiol dose and BMI on estradiol concentrations.

Results: 259 individuals (median age 25.8(IQR 21.9,33.5) years)) had data available for analysis. Median duration of estradiol therapy was 24(15,33) months. Median estradiol concentration was 328(238,434) pmol/L (89(65,118) pg/mL) on 6(4,8) mg estradiol valerate. 172 (66%) individuals had estradiol concentrations within the target range recommended in consensus guidelines. 70 (27%) individuals had estradiol concentrations below target, and 17 (7%) above target. There was a weak positive correlation between estradiol dose and estradiol concentration (r=0.156, p=0.012). There was no correlation between BMI and estradiol concentration achieved (r=-0.063, p=0.413).

Conclusions: 66% of individuals achieved estradiol concentration recommended in consensus guidelines with a relatively high oral estradiol dose. There was significant interindividual variability. Estradiol concentration should be interpreted in conjunction with clinical features of feminization and weighed against potential risks of escalating estradiol dose.

References

1. Cheung AS, Wynne K, Erasmus J, Murray S, Zajac JD. Position statement on the hormonal management of adult transgender and gender diverse individuals. Med J Aust 2019; 211:127-133

2. Angus L, Leemaqz SY, Ooi O, Cundill P, Silberstein N, Locke P, Zajac JD, Cheung AS. Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving estradiol therapy. Endocr Connect 2019
OR30-04 Autonomous Drone Delivery of Insulin
Authors: O’Keeffe Derek Timothy , Johnson Kevin , Maraka Spyridoula
Published: May 2020

Unmanned aerial vehicles (UAV’s) or drones have become ubiquitous in modern society, predominantly as recreational tools (e.g. racing, photography). However, their use to transport medical products is still nascent, with the best examples seen in emerging economies with underdeveloped infrastructure due to local terrain such as East African jungles or the South Pacific islands. A case in point is the drone operator Zipline, which has pioneered the delivery of blood products in Rwanda since 2016 [1]. Therefore UAV’s have potential in disaster relief operations where there is often significant disruption of health systems [2]. After Ireland experienced Storm Ophelia (Cat 3 Hurricane) in 2017 and then Storm Emma (Winter Blizzard) in 2018, many of our patients with Diabetes had issues with insulin supplies as they remained housebound due to subsequent flooding/snowdrifts. Diabetes Mellitus is one of the world’s most common chronic diseases with approximately 400 million people affected. Insulin is often needed to achieve and maintain glycemic control and therefore is considered a lifesaving medication for patients with diabetes [3]. Consequently, in order to ensure an adequate insulin supply method for patients, after a sentinel weather event, we developed a UAV delivery solution using a vertical take-off and landing (VTOL) Wingcopter 178 drone which we operated under beyond visual line of sight (BVLOS) conditions. After a lengthy planning process, we ensured compliance with all Irish (European) Aviation Aerospace regulations. In addition we complied with regulations surrounding the dispensing of prescribed fridge medications. We had our maiden flight on September 13, 2019 from Galway, Ireland to the Aran Islands (20Km each way) delivering insulin from the pharmacist to the patient’s clinician. This represents the first documented autonomous delivery of insulin for a patient with diabetes.

References 1. Ackerman E, Strickland E. Medical delivery drones take flight in east africa. IEEE Spectrum. 2018 Jan 1;55(1):34-5. 2. Rabta B, Wankmüller C, Reiner G. A drone fleet model for last-mile distribution in disaster relief operations. International Journal of Disaster Risk Reduction. 2018 Jun 1;28:107-12. 3. da Rocha Fernandes J, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P, Cavan D, Makaroff LE. IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes research and clinical practice. 2016 Jul 1;117:48-54.
SUN-548 Ketone Bodies in Critical Illness Alter Cholesterol Synthesis in Skeletal Muscle, Interlinked with Protection Against Weakness
Authors: Goossens Chloë , Derde Sarah , Perre Sarah Vander , Weckx Ruben , Boone Marissa , Van den Berghe Greet , Langouche Lies
Published: May 2020

Background: Critically ill patients often develop muscle weakness, which hampers recovery. In septic mice, supplementing parenteral nutrition (PN) with ketone body 3-hydroxybutyrate (3HB) attenuated muscle weakness, but also normalized sepsis-induced low cholesterol1. As 3HB can be metabolized into cholesterol, we hypothesized that improved muscle function with 3HB was related to altered cholesterol metabolism. Methods: In a catheterized, fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis (cecal ligation and puncture), septic mice received PN supplemented with either D,L-3HB sodium salt (PN+3HB; 150 mg/day) or isocaloric glucose (PN+gluc) and healthy pair-fed mice served as controls (n=15-17 mice/group). After 5 days, ex vivo muscle force and markers of cholesterol metabolism were assessed. In 600 weak and non-weak human critically ill patients (weakness assessed on day 8±1 in ICU by MRC sum score), serum total cholesterol concentration was measured on ICU day 3 or last day for shorter stayers. Results: In mice, PN+3HB counteracted the sepsis-induced lowering of plasma cholesterol (p=0.04), which correlated positively with absolute muscle force (R2=0.19, p=0.002). Plasma mevalonate concentration, a surrogate marker of cholesterol synthesis, was reduced by sepsis (p=0.03 vs. controls), but normalized by PN+3HB (p=0.001 vs. PN+gluc). Skeletal muscle expression of cholesterol synthesis genes Srebf2, Hmgcr and Hmgcs1 was higher in PN+3HB than in PN+gluc septic mice (p≤0.01). Expression of cholesterol uptake receptor Ldlr was also increased in PN+3HB septic mice (p=0.02 vs. PN+gluc), whereas PN+3HB did not affect cholesterol efflux transporters. In contrast, PN+3HB did not alter sepsis-induced alterations in markers of hepatic cholesterol metabolism. Plasma concentration of ubiquinone, a central co-factor of the mitochondrial respiratory chain derived from mevalonate, was increased by sepsis, irrespective of PN+3HB (p<0.0001 vs. controls) and PN+3HB could not counteract sepsis-induced muscular mitochondrial dysfunction (p≤0.0009 vs. controls). This excludes the involvement of ubiquinone in muscle weakness attenuation by 3HB supplementation. However, higher muscular Nceh1 expression was observed with PN+3HB (p≤0.04 vs. controls and PN+gluc), suggesting enhanced shuttling of newly formed free cholesterol to the membranes. In human ICU patients, lower serum cholesterol concentration was observed in weak vs. non-weak patients (p=0.0002). In a multivariate model adjusted for baseline risk factors, low serum cholesterol concentrations were independently associated with muscle weakness (p=0.05). Conclusion: 3HB supplementation of PN enhanced muscle cholesterol synthesis and increased plasma cholesterol, which appeared to independently protect against sepsis-induced muscle weakness. 1 Goossens et al. (2019). Crit Care. 23: 236.
SUN-669 The G209R Mutant Mouse as a Model for Human PCSK1 Polyendocrinopathy
Authors: Shakya Manita , Gahlot Surbhi , Arunagiri Anoop , Hassan Anis , Arvan Peter , Low Malcolm James , Lindberg Iris
Published: May 2020

A striking number of SNPs and rare mutations have been identified in PCSK1, the gene that codes for the enzyme proprotein convertase 1/3 (PC1/3) which proteolytically activates prohormones within the secretory pathway. All infants bearing two copies of catalytically inactivating mutations, including G209R, exhibit severe neonatal malabsorption requiring parenteral nutrition for months and subsequently develop additional endocrinopathies, often including diabetes and obesity. In order to create a mouse model to explore the underlying mechanism of the malabsorption phenomenon and the endocrinopathies, a G209R point mutation was introduced into exon 6 of mouse Pcsk1 using CRISPR-Cas9 genome editing. Fifty-six live pups were collected at postnatal days one or two; however, most homozygous G209R mutant pups succumbed by day 2, and surviving pups were severely dwarfed. In homozygous, but not heterozygous pups, blood glucose levels were significantly lower with elevated plasma insulin-like immunoreactivity and accumulation of unprocessed proinsulin in G209R pancreas compared to the wild type pups from the same litters. The POMC product α-MSH (produced by PC2 from PC1/3-generated ACTH) has been strongly implicated in obesity mechanisms. We found pituitary POMC processing to ACTH was also affected by the G209R mutation in combined anterior and intermediate pituitary lobes. ACTH was markedly reduced in homozygote pituitary, with significant accumulation of POMC. Using Western blotting, we observed a significant reduction in PC1/3 protein in homozygote brains, while PC2 protein levels remained unaffected. Most likely due to the continued presence of PC2, pituitary and brain levels of α-MSH were not impaired, suggesting that α-MSH itself is not involved in the phenotype. Prior studies have shown that G209R PC1/3 is not efficiently trafficked out of the ER; further studies will examine the contribution of misfolded G209R PC1/3 to possible cellular ER stress, as well as determine peptide hormone levels in brain and peripheral tissues.
MON-914 Ectopic ACTH Syndrome Caused by Adenocarcinoma of Lung - a Rare Association with Rare Complication
Authors: Tickoo Vidya , Boddula Raman , Vottery Ravindra , Venkatanarasu Ashok , Reddy Aashish , Basavaraju Santosh , Chinte Chimutai , Sheth Kaushal
Published: May 2020

INTRODUCTION Ectopic ACTH constitutes 5-10% of ACTH dependent Cushing’s syndrome. Evolution of symptoms can be rapid. Cortisol & ACTH is usually higher as compared to Cushing’s disease. Imaging studies should be obtained for localization of the source of ACTH. Here, we present a case of Cushing’s syndrome caused by ectopic ACTH production caused by adenocarcinoma lung, which has very rarely been associated with this syndrome CASE A 52-year-old male presented with 3-month H/O bilateral pedal edema & puffiness of face. He noticed bruises over his trunk & darkening of face for 2 months. There was a recent worsening of his HTN (requiring 3 antihypertensives) & recently diagnosed with DM. On examination patient had cushingoid features, acne and ecchymosis. BP - 166/110 mm Hg. Proximal myopathy, Pedal edema, clubbing & cervical lymphadenopathy was present (largest node - 2.5cm). Fasting & postprandial blood sugars were 190 & 285 mg/dl respectively. Serum K+ was 3.0 meq/L (3-5-5.0meq/L), 11pm serum cortisol was 51.6 mcg/dl (cutoff < 7,5mcg/dl), 8 am cortisol after overnight 1mg dexamethasone was 60.7 mcg/dl (cutoff<1.8mcg/dl). Serum ACTH(8am) - 178 pg/ml.(>20 pg/ml-ACTH dependent Cushing’s) Biopsy of neck node revealed poorly differentiated adenocarcinoma. PET scan showed left lung upper & lower lobe masses. A diagnosis of ectopic ACTH syndrome was made, the source of which was adenocarcinoma of lung, which has been very rarely reported to be associated with it. Oral ketoconazole was started followed by Chemotherapy with paclitaxel & carboplatin. Within the next 7 days patient developed pleural effusion, neutropenia & worsened rapidly. BAL revealed Nocardia species, known to be associated with hypercortisolism. He was treated with appropriate antibiotics & supportive treatment but succumbed to septic shock. CONCLUSION If a patient presents with rapidly evolving symptoms of Cushing’s syndrome, ectopic ACTH syndrome should be considered. The presence of wasting and weight loss, hypokalemic alkalosis, pedal edema & marked hyperpigmentation should also alert towards the diagnosis. Histopathological confirmation of malignancy is important, as in our case with ectopic ACTH where the source was an adenocarcinoma of the lung, of which only 5 cases have been reported till now (Ectopic ACTH more commonly associated with SCLC). Finally, in cases of severe hypercortisolemia, there should be a high index of suspicion for opportunistic infections including invasive fungal infections, Nocardiosis etc, so that specific antibiotic therapy can be initiated. Typical features like fever, leukocytosis can be absent. Treatment of underlying hypercortisolism with surgical/medical management prior to initiation of chemotherapy has been shown to reduce the frequency of infections.
SUN-051 Gender Dysphoria - Data from One Hundred Patients
Authors: Ferreira Maria João , Castedo José Luis , Pedro Jorge Pires , Salazar Cristina Daniela , Costa Cláudia Fernandes , Carvalho Davide M
Published: May 2020

Introduction: Gender dysphoria (GD) is a disease in which the patient's gender identity does not correspond to their biological gender. Traditionally, sex is assigned accordingly to the sexual organs as male or female, however these patients do not identify with this classification. A biological male who identifies himself as a female is referred to as transgender female or male to female GD (MtF) and a biological female who identifies herself as a male is referred to as a transgender male or female to male GD (FtM). In our center there is a multidisciplinary consultation to approach and follow up patients with GD. Our work is an analysis of the patients who are currently attending this consultation. Methods: Retrospective study of patients attending the Sexual Medicine Group Consultation with diagnosis of GD. Results: 100 patients diagnosed with GD, of which 65% had GD FtM and 35% MtF. The median age is 25 years (± 9.5 years). Regarding the onset of symptoms, 76% of patients report that it occurred in childhood (before age 10); 20% from 10 to 18 years old and only 4% reported having occurred after 18 years. The median age for starting treatment is at 22 years (± 7.5 years). About 83% of the patients start therapy on medical advice, the remaining are self-medicated; 86% of FtM GD patients are currently on testosterone therapy; 85% of MtF GD patients are on estrogen therapy and 71% on anti-androgens. Concerning co-morbidities: 22% of patients have depression; 39% smoke; 6% are HIV-infected; 4% dyslipidemia and 2% hypertension. 47 (47%) patients underwent at least one surgical treatment; the average time to the first surgery was 2 years. Of the FtM GD patients, 23 (35%) patients underwent mastectomy, 10 (15%) hysterectomy and oophorectomy and 3 (5%) neophaloplasty; of the MtF GD patients 8 (23%) underwent augmentation mammoplasty; 7 (20%) neovaginoplasty. Two patients had a family history of GD. One case of Klinefelter’s syndrome and one case of congenital adrenal hyperplasia was diagnosed during the study prior to therapy initiation.

Discussion: There was a higher prevalence of FtM compared to MtF, unlike most centers reporting a higher prevalence of MtF. Regarding the proportion of patients on medical therapy, the data are in line with data from other centers already published, as well as the fact that most patients in our study are young. Conclusion: The demand for medical help from GD patients is increasing. The evaluation of these patients by endocrinology before and throughout treatment is essential, not only for the evaluation of contraindications or side effects of therapy, but also for the identification of endocrinological diseases. This is the first work, to our knowledge, to portray the case series of a consultation center dedicated to the treatment of patients with GD in Portugal.
SAT-151 Regulation of Low-Density Lipoprotein Receptor Expression in Triple Negative Breast Cancer
Authors: Scully Tiffany , Kase Nathan G , Gallagher Emily Jane , LeRoith Derek
Published: May 2020

Preclinical models and clinical studies suggest that hypercholesterolemia promotes breast cancer progression 1,2. The expression of the low-density lipoprotein receptor (LDLR) has been positively associated with poorer recurrence-free survival in human breast cancer studies 3. Mechanistically, LDLR has been demonstrated to play a role in the increased tumor growth associated with hypercholesterolemia, as knock-down of LDLR led to decreased tumor growth in setting of elevated circulating LDL cholesterol. The aim of this study was to identify factors which up-regulate expression of LDLR in triple negative breast cancer (TNBC). In glioblastoma, hyper-activation of the epidermal growth factor receptor (EGFR) signaling pathway has been associated with greater LDLR expression and susceptibility to targeting of cholesterol metabolism4. As EGFR is frequently expressed in TNBC5, we examined if increased LDLR expression is associated with activation of the EGFR signaling pathway in TNBC. The expression of LDLR in the TNBC cell lines, MDA-MB-231 (231) and MDA-MB-468 (468) was examined pre- and post-EGF stimulation of the EGFR and in the presence of chemical inhibitors. Cells were grown in DMEM/10% FBS/1% Pen/strep (P/S), and experiments were performed under reduced serum conditions at 1.25%FBS/DMEM/1%P/S. In the absence of stimulation, LDLR protein expression was 3-fold higher in 231 vs 468 cell lines. This was despite mRNA expression being comparable at baseline, suggesting that the difference in protein expression was post-transcriptionally mediated. Treatment with 10 ng/mL EGF for 2 hours led to an increased activation of the EGFR, phosphorylation of Akt and extracellular signal regulated kinase (ERK) in both cell lines but induced an increase in LDLR protein and mRNA expression only in 468 cells. Treatment of 468 cells with EGF after exposure to actinomycin, a transcription inhibitor, revealed that EGF treatment resulted in reduced degradation of LDLR mRNA (p = 0.002) over 3 hours, suggesting that the EGF-induced increase in LDLR expression was by protection of LDLR mRNA from degradation. Chemical inhibition of the ERK pathway with 20 μM UO126 reduced both the EGF-induced increase in LDLR expression in 468 cells (p = 0.015) as well as the high baseline expression of LDLR by half in 231 cells (p = 0.001). Overall our results suggest that the EGFR/ERK signaling pathway regulates LDLR expression in TNBC, supporting the increased anabolic needs of this aggressive, swiftly expanding form of breast cancer.

References: 1Alikhani, N. et al., Oncogene32, 961-967 (2013), 2Pelton, K. et al., Am. J. Pathol.184, 2099-2110 (2014), 3Gallagher, E. J. et al., Oncogene36, 6462-6471 (2017), 4Guo, D. et al., Cancer Discov.1, 442-456 (2011), 5Reis-Filho, J. S. & Tutt, A. N. J. Histopathology52, 108-118 (2008).
SAT-237 Isolated Hypogonadotropic Hypogonadism in a Male with Sarcoidosis
Authors: Matos Tânia , Costa Cristiana , Vale Sónia do , Bugalho Maria Joao
Published: May 2020

Sarcoidosis is a systemic disease of unknown cause that is characterised by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. The clinical involvement of the nervous system occurs in 5 to 15% of the cases. Any part of the nervous system can be affected, with the cranial nerves, the hypothalamus and the pituitary gland being the ones most commonly involved. However, hypothalamic-pituitary (HP) manifestations are rare manifestations of sarcoidosis, occurring in <1% of all intrasellar lesions. A 33-year old man was admitted to the emergency room with confusion and cognitive impairment progressively evolving over the past 2 months. The main complains were bilateral headaches, fatigue, adynamia and libido reduction. No visual fields defects were detected. Three months earlier, he had been diagnosed with sarcoidosis with pulmonary and ganglionar involvement, which was confirmed after histopathology analysis of tissue biopsy of the lung and mediastinic lymph nodes. However, the patient remained without any medication. He was admitted to the in-patient department and a brain MRI was performed, which revealed intense infra and supratentorial leptomeningeal enhancement, with involvement of the hypothalamus and optic chiasm. Laboratory evaluation revealed significantly reduced gonadotrophin and testosterone levels (FSH 1.1U/L, LH 0.43U/L, total testosterone 4.5ng/dL), normal prolactin and no other HP hormonal deficits. Clinical diagnosis was consistent with neurosarcoidosis with hypothalamic infiltration resulting in clinical hypogonadotropic hypogonadism. The patient initiated systemic therapy with corticosteroid, showing an overall improvement. After the hospital discharge, he started hormonal reposition with testosterone therapy with additional clinical improvement. Pituitary insufficiency is the presenting form of neurosarcoidosis in only 3 to 9% of the cases. Aside from diabetes insipidus and hyperprolactinemia, hypogonadism represents one of the endocrine disorders more frequently associated with HP involvement. Furthermore, hypothalamic sarcoidosis involvement is usually associated with multiple hypothalamic-pituitary deficits, rather than isolated ones. The case reported herein, illustrates a presumptive case of neurosarcoidosis, conducting to an isolated hypothalamic-pituitary axis deficiency. Although rare, HP involvement in neurosarcoidosis is usually associated with permanent endocrine defects. Hence, hypothalamic-pituitary axis evaluation should be performed promptly and long-term management is required.
Walt Whitman’s Formalism
Authors: Winant Johanna
Published: May 2020

In this article, the author argues that we should understand Walt Whitman’s catalog as a poetic form that is also a logical form — enumerative induction. Whitman’s catalogs — his characteristic technique of generating long lists — have long been recognized as central to his poetics. The list, or enumeration, is also the most basic form of inductive reasoning. By recognizing that Whitman reasons logically through his poetic form, not only is the common account of Whitman changed, but the concept of form must be revised in three crucial ways. First, form should not be defined in opposition to poetic content— this is a false definitional binary. Second, form and free verse are another false binary, as poems can be written in free verse and also have form, as Whitman’s poetry is and does. Third, form is not just a rubric with which critics interpret poems but the logic by which poems interpret the world.
Ephemerality
Authors: Siddiqi Anooradha
Published: May 2020

What are the politics of ephemerality? In the United Nations High Commissioner for Refugees establishment at Dadaab, Kenya, a massive complex of refugee camps near the border of Somalia, the visual and architectural terms of ephemerality—a permanent impermanence—transform the act of seeing. By thinking through one refugee's experience and analyzing urbanism, architectural form and symbolism, and spatial-political organization, this essay suggests that ephemerality plays a part in structuring subjectivity, with implications for the narration of history.
The Urbanism of Racial Capitalism
Authors: Herscher Andrew
Published: May 2020

Emerging in British agricultural discourse in the seventeenth century, the term blight moved from agriculture to culture, and so from countryside to city, in the context of the industrializing American city of the early twentieth century. This city housed increasingly large populations of reserve labor and provided increasingly large spaces to accommodate that population. Defined as “blight,” the spaces occupied by reserve labor were expelled from the very system that produced them: those spaces become obstacles to property development, as opposed to products of a disavowed form of de-development. As race has been the principal medium of difference that has legitimized and stabilized the hierarchical social order of industrial capitalism, the management of “blight” also inscribed race in urban space. A long but continuous line therefore connects the political definition of “black”—in terms of an absence of the full rights of persons, from the era of enslavement, through the era of segregation, to the present—with the political definition of “blight” in terms of an absence of full rights to property from the era of urban renewal into present-day austerity urbanism.
Propulsions
Authors: Asher Thomas , Akoth Steve Ouma
Published: May 2020

This essay foregrounds mobility in cities in the global South in order to recast our current understanding of how informal settlements function and how residents of these neighborhoods navigate increasingly feral economies. Focusing largely on an informal settlement in Nairobi, Kenya, the piece explores the social worlds animated by mobility, bringing renewed attention to social and spatial practices. These include strategies of economic and social cooperation used by residents to spatially constitute communities, imbue them with meaning, and in the process create ladders to opportunity. The essay also demonstrates that when development agencies and advocates of the urban poor operate without a sociological understanding of the role of mobility, the results can be devastating.
Mis/translation, Colonialism, and Environmental Conflict
Authors: Østmo Liv , Law John
Published: May 2020

This article describes a colonial encounter in north Norway between Sámi practices for fishing and knowing the natural world, and the conservation policies of state policy makers. In Sámi practices the world is populated by powerful and morally lively human and nonhuman actors. In caring for the land and its lakes in practical ways it is important to sustain respectful relations with those actors. Norwegian environmental policy works differently by distinguishing between nature and culture and seeking to protect landscapes from what it takes to be human interference, so that natural forces can operate unimpeded. The article first explores these two different worldviews and shows how environmental policy imposes restrictions on fishing practices that make it difficult or impossible for Sámi fisherpeople to care for and sustain respectful relations with their lakes. It then reflects on the significance of translation and mistranslation for this encounter, noting that important environmentally relevant Sámi words translate poorly into Norwegian or English, and that the practices that these index are ignored or misunderstood in those translations. In particular, it focuses on the notion of jávredikšun, a key term for Sámi people who fish on inland lakes, and shows that the word indexes environmental actions and realities that translate only with difficulty into English. Finally, it considers the potential political and analytical significance of refusing translations of this and other important environmentally relevant indigenous words.
Features of Financial Audit of the Revaluation of Fixed Assets Treatment in the Financial Statements
Authors: Sotnikova Lyudmila
Published: May 2020

Th e article discusses the features of fi nancial audit of the refl ection in the accounting (fi nancial) statements of audited entities of the results of the revaluation of fi xed assets. Th e need for a thorough check is due to the fact that from January 1, 2020, it became mandatory to use the balance sheet method of accounting for diff erences between the accounting and tax values of assets and liabilities at the reporting date.
Trust As an Audit Philosophy
Authors: Arabyan Knarik
Published: May 2020

Th e article presents the hierarchical level structure of the theory of audit and examines in detail the fi rst worldview level of audit theory, which is an audit philosophy based on trust. In conditions of uncertainty and increased risks, the category of «trust» takes on a new very important meaning. In audit activities, the relationship between the auditor and the audited entity is built on trust, which subsequently transforms into confi dence and forms an opinion regarding the reliability of the accounting (fi nancial) statements.
ACCUMULATION OF HEAVY METALS BY PULSE CROPS UNDER THE APPLICATION OF BIOLOGICALLY ACTIVE SUBSTANCES IN THE VOLGA REGION FOREST-STEPPE
Authors: Trots N. , Pakhomov Aleksei
Published: May 2020

The aim of study is reduction of accumulation of heavy metals in agrocenosis of pulse crops due to the action of biologically active substances in the conditions of the middle Volga forest. An experiment study in order to reveal the effect of pre-sowing seed treatment with biologically active substances on the accumulation of heavy metals by soils and plants in agrocenoses of peas and soybeans was conducted in 2013-2015. The results of pre – sowing treatment of soybean seeds of the Samer 3 breed and peas of the Flagman 12 with the Rizotorfin and Rizotorfin in combination with analogues – Agrica and Humariz biologically active substance are presented. The analysis of heavy metals content in soil and plant samples was performed in the laboratory of the «Samara agrochemical ser-vice» Station by method of atomic adsorption spectroscopy. It is established that the introduction of biologically ac-tive substances into the soil containing heavy metals can reduce the concentration of their mobile forms and restrict access to grain. The content of mobile forms of elements in the soil under soybean growing areas, in comparison with the control, decreases: lead by 1.14 times when treated with Rhizotorphin+Humariz, cadmium – 1.18 times when treated with Rhizotorphin, copper – 1.2 times and cobalt – 2.0 times under the influence of the combination of Rhizotorphin and Agrica. According to the coefficients of biological absorption of pea and soy grains, the studied heavy metals are referred to the elements of biological capture of CАB<1. An effective inactivating effect on heavy metals is provided by pre-sowing treatment of pea and soy seeds with biologically active substances combined with Rhizotorphin+Agrica and Rhizotorphin+Humariz.
NITROGEN CONTENT IN SOIL AND NITRATE REDUCTASE ACTIVITY IN WINTER WHEAT LEAVES WITH THE USE OF NITROGEN FERTILIZERS
Authors: Bakaeva Natalya
Published: May 2020

The purpose of the study is increasing the efficiency of using nitrogen fertilizers and its effect on nitrate-reducing capacity of the leaf apparatus. The research was conducted in 2016-2018 in the Central zone of the Samara re-gion. The predecessor is complete fellow. Svetoch winter wheat elite seed varieties were used for sowing. Seeding was carried out in the experimental fields of the laboratory «Agroecology» of the Samara state University. Nitrate and ammonium nitrogen content in soil layer of 0-30 cm depth was estimated before planting and after plant nutri-tion with nitrogen fertilizers in regard to the growth phases (tillering, elongation and heading), the content of nitro-gen, protein and nitrate reductase enzyme activity in leaves during plant development. Dynamics changes of nitro-gen content in the soil and after fertilization with nitrogen shows that during vegetation period of plants, the amount of nitrogen is sufficient for their growth. As the phenological phases of plants change, the content of nitrogen and protein in winter wheat leaves increases, and activity of the enzyme nitrate reductase lifts, which catalyzes nitrate regeneration to nitrite. The value of the activity of the enzyme nitrate reductase in leaves can serve as a criterion for evaluating the availability of plants with the nitrate form of nitrogen. In future, the activity of this enzyme can be used as an indicator of optimizing nitrogen nutrition of plants aimed at metabolic processes. The use of various nitrogen fertilizers, and to a greater extent ammonium nitrate, increased the supply of plants with nitrogen, which is later used by them in the reutilization of nitrogen from leaves to the emerging seed, thus contributing to quality of grain.
FOLIAR FEEDING EFFECTIVENESS DURING WHITE MUSTARD CULTIVATION
Authors: Naumtseva Kseniy , Vinogradov Dmitryi
Published: May 2020

The purpose of the research is increasing the yield of white mustard varieties by using complex liquid fertilizers in Ryazan region. The research was conducted in 2018-2019 on the fields of the experimental agro-technological station of Ryazan state agro-technological University («Agrotechno-Park»). The soil of the experimental site is gray forest. In 2019, the area under oil producing crops in Ryazan region was more than 151 thousand hectares, the mustard sown area amounted to 9.5 thousand hectares.Two experiments were performed in 4-fold replication. Complex liquid fertilizer in both experiment 1 and experiment 2 provided intensive plant growth and increased pho-tosynthesis rates. The largest number of oilseeds in experiment 1 was obtained on the Lucium breed, variant Azotovit 1 l/ha + Phosphatovit 1 l/ha + Rauactive 1 l/ha – 20.5 C/ha, which is higher than in the control by 3.1 C / ha. Chaika – breed was17.4 C/ha and Rapsodia one –18.5 C/ha (on average over the years of research). Experiment 2 was characterized by the maximum increase in yield of the Lucium breed – 13.1 C/ha (on average per 2018-2019) – on the Active Boron one 1 l/ha + Active Zinc 1 l/ha. Studies of 2018-2019, showed that in practice of agriculture in the region in agrocenoses of white mustard can be used complex liquid fertilizer Azotovit, Fosfatami, Reactiv – pro-cessing phase from 2 to 4 true leaves + phase budding (consumption rate 1.0 l/ha) and complex preparations, Zinc Asset and Asset Bor – processing phase of button rosette + the budding phase (consumption rate 1.0 l/ha).
EFFICIENCY OF APPLICATION OF ORGANOMINERAL FERTILIZERS IN ORDER OF HEAVY METALS INACTIVATION WHEN GROWING POTATOES IN SAMARA VOLGA STEPPE ZONE
Authors: Chernyakova Galina , Trots N. , Kostin Ykov
Published: May 2020

The aim of the research is increasing the productivity of potatoes via the use of organic fertilizers. Research was carried out on crop rotation fields with potato plantations of Arnica and Arosa breeds. The distance between the ridges is 75 cm, the ridge height is 18-20 cm, and the distance between seats in a row is 24 cm. In the applied crop rotation, potato was planted on fallow steam. The object of study is the soil of the upper farm field (0-30 cm). The results of applying programmed soil fertilizers for potato plants consisting of background mineral fertilizers N120P150K300 and manure in doses of 20 t/ha and 60 t/ha for four experimental plots with an area of 210 ha are pre-sented. Determination of heavy metal content was performed within the certified laboratory of the Federal state Uni-versity «Station of agro-chemical service «Samara» by atomic absorption spectroscopy. Based on the results of heavy metals mobile forms in the soil, a concentration coefficient was calculated, which showed that the actual av-erage value exceeds the background level. The lead concentration coefficient amounting to 1.6 – indicates the ac-cumulation of the element on the research area. Organo-mineral fertilizer N120P150K300+manure 60 t / ha allows you to restore the balance of mould on the research ordinary Chernozem, get an increase in yield of 4.1-8.9 t / ha, has an effect on reducing the content of gross heavy metals in the soil: Cd – by 1.2-1.4 times; Cu – 1.1-1.2 times, Pb, Zn, Mn and Fe – 1.1 times compared to the control area. Within the experiment N120 P150K300 + manure 60 t / ha lead mobility reduces to 3.9%, copper, zinc, iron-less than by 1 %, cadmium mobility increases by 3.4-5.7 %.
MILK OF BLACK-WHITE COWS WITH DIFFERENT GENES OF CAPPA CASEIN AND DIACYLGLYCEROL OF O-ACYLTRANSFERASE FOR CHEESEMAKING
Authors: Shaydullin Radik , Sharafutdinov Gazimzyan , Moskvicheva Anastasiy
Published: May 2020

The purpose of the research is improving the quality and technological properties of milk from black-and-white cows. The research was conducted on first-calf cows of a black-and-white breed in LLC «Dusym» of the Atninsky district of the Republic of Tatarstan. Three groups of experimental cows were formed depending on the genotype of CSN3 and DGAT1, which have equal lactation month. Cheese making milk obtained from cows with different allelic variants of the kappa-casein and diacylglycerol O-acyltransferase genes was studied. DNA testing was performed on the CSN3 and DGAT1 genes of experimental cows and allelic variants of these genes were determined by pol-ymerase chain reaction followed by analysis of restriction-site polymorphism. It was found that milk of cows with the genotype CSN3 AB and CSN3 BB, when exposed to rennet, showed a better yield of a dense casein clot (80 and 100%) and separation of serum (P <0.05), with a shorter coagulation time (20.3 and 16.5 min; P <0.05-0.01). Ac-cording to the DGAT1 gene, first-calf milk with the allelic variant DGAT1 AK and DGAT1 KK had the advantage, respectively, 86.7% and 85.7%, 24.0 and 25.7 minutes. The worst milk coagulation time is typical for CSN3 AA group – 29.5 minutes and DGAT1 AA one – 30.4 min. In terms of milk coagulation time, type II (15-40 min.) groups have the genotype CSN3 AB and CSN3 BB with the largest share of cows in the herd – 80.0 and 71.4% and with the genotype DGAT1 AK and DGAT1 KK – 86.6 and 85.7%, respectively. Thus, milk obtained from cows with the kappa-casein gene allele B and the diacylglycerol O-acyltransferase gene allele K gene in the genotype has the best cheese-making properties.
A MITOLOGIA BRASILEIRA EM A BANDEIRA DO ELEFANTE E DA ARARA, DE CRISTOPHER KASTENSMIDT
Authors: Magalhães Sérgio
Published: May 2020

Recebido em 09 Mar 2020.Aprovado em 14 Abr 2020.