bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-473 Thyroid Dysfunction in a Patient with Malignant Melanoma Treated with Immune Checkpoint Blockade
Authors: Gupta Shaveta , Yin Ngwe 
Published: May 2020

Abstract
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

Abstract
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

Abstract
Background: ACTH-producing pheochromocytomas (APP) are a rare cause of ectopic Cushing’s syndrome (CS), representing &lt;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, [&lt;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

Abstract
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

Abstract
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

Abstract
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&lt;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

Abstract
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

Abstract
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 &lt; 7,5mcg/dl), 8 am cortisol after overnight 1mg dexamethasone was 60.7 mcg/dl (cutoff&lt;1.8mcg/dl). Serum ACTH(8am) - 178 pg/ml.(&gt;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

Abstract
Introduction: Gender dysphoria (GD) is a disease in which the patient&#39;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.