bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-350 Bone Marrow Adipose Tissue Is Associated with Fracture Prevalence in Anorexia Nervosa
Authors: Dang Tran , Faje Alexander T , Meenaghan Erinne , Bredella Miriam , Klibanski Anne , Fazeli Pouneh K 
Published: May 2020

Abstract
Anorexia nervosa, a psychiatric disorder predominantly affecting women, is characterized by self-induced starvation, low body weight, low subcutaneous and visceral fat depots, and low bone mass. More than 85% of women with anorexia nervosa have bone mineral density (BMD) values more than one standard deviation below the mean of women of comparable age. Although there is a significantly increased risk of fracture in women with anorexia nervosa, low BMD has not been shown to consistently predict the increased fracture rate in this population. Despite low subcutaneous and visceral adipose tissue stores, women with anorexia nervosa have increased bone marrow adiposity, which is inversely associated with BMD. We hypothesized that increased bone marrow adipose tissue would be associated with the increased fracture rate in women with anorexia nervosa. We studied sixty-two women: 34 with anorexia nervosa (mean age + SEM: 28.3 + 0.9 years) and 28 normal-weight controls of similar age (28.3 + 1.1 years; p=0.72). We examined associations between lifetime self-reported fracture history and 1) BMD of the lumbar spine (L1-L4), lateral spine (L2-L4), total hip, and femoral neck measured by dual energy X-ray absorptiometry and 2) bone marrow adipose tissue at the spine (L4 vertebra) and hip (femoral metaphysis, diaphysis and epiphysis) measured by 1H-magnetic resonance spectroscopy. Women with anorexia nervosa had significantly lower BMD at the spine and hip (p&lt;0.0001 at all sites) and significantly higher bone marrow adipose tissue at the L4 vertebra (p&lt;0.0001) and femoral metaphysis (p=0.001) as compared to normal-weight controls. Forty-seven percent (n=16) of women with anorexia nervosa versus 39% (n=11) of normal-weight controls reported a lifetime history of fracture (p=0.54). In women with anorexia nervosa, there was no significant association between fracture history and BMD at the spine or hip (p=0.27-0.98). In the group as a whole, bone marrow adipose tissue was greater in the L4 vertebra in individuals with a history of fracture compared to those without a fracture history (p=0.02). In subjects with anorexia nervosa, those with a history of fracture had greater bone marrow adipose tissue at the L4 vertebra (p=0.01) and femoral diaphysis (p=0.01) compared to those without a history of fracture; these differences in bone marrow adipose tissue remained significant after controlling for BMI (p=0.01-0.03) and also after controlling for BMD (p&lt;0.01 for both). Higher bone marrow adipose tissue is associated with increased fracture prevalence and may be a better predictor of fracture risk than BMD in women with anorexia nervosa. Future prospective studies will be necessary to better understand the association between bone marrow adiposity and fracture risk in this population.
MON-615 Retrospective Analysis of the Contribution of Cannabis Usage to Diabetic Ketoacidosis at an Urban Teaching Hospital
Authors: Kha Christine K , Phan Ellyn , Simon Nicole 
Published: May 2020

Abstract
Diabetic ketoacidosis (DKA) is an acute life-threatening complication of diabetes mellitus. It is responsible for greater than 100,000 hospital admissions per year in the US (1). There are few studies regarding the relationship between drug usage and acute diabetic complications (2). Since 2001, cannabis usage among US adults have more than doubled, as state legal restrictions have eased and attitudes towards cannabis have become more permissive. Cannabis is the most commonly used illicit drug in the US (3). Some studies suggested cannabis usage was associated with improvement in insulin sensitivity and pancreatic beta cell function. Other research demonstrated cannabis usage may contribute to diabetes-related hospitalizations.
A retrospective analysis was performed at an urban teaching hospital to examine the relationship between cannabis usage and risk for DKA upon presentation. From March 2017 to February 2019, all non-pregnant patients aged 18 years and older, and who met criteria for DKA admission upon medical records review, were included in the study. Demographics, vitals, biochemistry, and toxicology were evaluated. Overall, 188 admissions for DKA were identified in a total of 130 patients, and 43% (81/188) were readmissions by 23 patients.
Illicit substance usage was addressed by history in 72% (135/188) of all admissions, among which 24% (33/135) reported cannabis usage. 36% (67/188) of all admissions, 73% (24/33) of the self-reported cannabis usage group, and 46% (37/81) of the readmissions, underwent general toxicology screening that did not include detection for cannabis. 11% (20/188) of all admissions, 24% (8/33) of the self-reported cannabis usage group, and 16% (13/81) of the readmissions, completed toxicology screening specifically for cannabis.
All of the self-reported cannabis usage admissions (33/33) and readmissions (81/81) presented with additional aggravating factors for DKA such as medication noncompliance, polysubstance abuse, and infection. Finally, 20 of the overall 130 patients admitted during this timeframe presented with new onset DKA, where none reported cannabis usage, 20% (4/20) completed general toxicology screening, and none underwent cannabis specific toxicology screening.
From the observational retrospective analysis at this hospital, there is a need for awareness about substance abuse screening, especially in adults with a history of recurrent hospital admissions for DKA. Knowledge among health care providers and patient education regarding the effect of cannabis usage on metabolic factors and its diabetes complications, including diabetes self-management at time of drug usage, can be further explored in prospective studies.
References: (1) Umpierrez (2006) Diabetes Care, 29(12), 2755-2757. (2) Brown et al., (2017) JAMA, 317(2), 207. (3) Haffajee et al., (2018) NEJM, 379(6), 501-504.
SUN-257 Evidence that Urocortin 2 Contributes to the Suppressive Effect of Metabolic Stress on LH Secretion in Female Mice
Authors: McCosh Richard B , Kreisman Michael J , Tian Katherine , Breen Kellie M 
Published: May 2020

Abstract
Pulsatile luteinizing hormone (LH) secretion is disrupted by numerous stimuli including metabolic stress. Insulin-induced hypoglycemia is a model of metabolic stress that suppresses LH secretion in numerous species including mice. Our recent work provides evidence that this inhibition of LH secretion occurs via suppression of neurons that contain kisspeptin (Kiss1), neurokinin B (NKB) and dynorphin (Dyn) in the arcuate (ARC) nucleus (KNDy cells). Thus, our current objective is to identify the neural components responsible for the suppression of KNDy cells during metabolic stress. Several lines of evidence support the hypothesis that the neuropeptide urocortin 2 (UCN2) has a key role in the inhibition of LH during stress in rats. First, ICV injection of UCN2 suppresses LH secretion. Second, an antagonist to the receptor for UCN2 reverses the suppression of LH during metabolic stress. Finally, restraint and osmotic stress increase UCN2 mRNA abundance in the paraventricular nucleus (PVN). To determine if UCN2 neurons in the PVN are activated during metabolic stress we performed immunohistochemistry for UCN2 and c-Fos in tissue collected 120 min after saline or insulin (0.75mU/kg) injection (n = 2/group, ovariectomized, adult, C57/BL6). Insulin significantly increased both the number of UCN2 cells (saline: 109.0 ± 8.5, insulin: 156.3 ± 10.8 cells) and the percentage of UCN2 cells that expressed c-Fos (saline: 13.1 ± 2.5%, insulin: 31.2 ± 0.8%). Next, we administered UCN2 (7.23nmol) via ICV injection to determine if this molecule suppresses LH secretion and/or mRNA abundance of KNDy genes. LH was measured in serial blood samples collected from 60 min prior to and 30-90 min following injection. Tissue was collected 3 h after ICV injection to confirm injection site and quantify mRNA abundance in ARC micropunches. In saline-treated mice (n = 5 successful injections), mean LH concentration and the number of LH pulses did not differ across sampling periods (mean: 6.4 ± 0.4 ng/mL vs. 6.0 ± 0.4 ng/mL; pulses: 2.6 ± 0.2 vs. 3.0 ± 0.3, pre vs. post). In contrast, in mice with successful UCN2 injections (n = 4) there was a significant reduction in both mean LH and the number of LH pulses following UCN2 (mean: 5.0 ± 0.3 ng/mL vs. 1.4 ± 0.2 ng/mL; pulses: 3.0 ± 0.0 vs. 0.25 ± 0.25, pre vs post). UCN2-treated animals had a significant reduction in the abundance of mRNAs encoding Kiss1 (~35%) and NKB (~40%) compared to saline-treated animals; the abundance of Dyn mRNA did not differ between treatments. These data demonstrate that PVN UCN2 cells are activated during metabolic stress and that UCN2 is sufficient to suppress LH secretion and the expression of genes involved in stimulating LH pulses. These data support the hypothesis that UCN2 released from neurons in the PVN impairs KNDy cell function and LH secretion during acute stress.
SAT-211 Is Doxazosin the Right Choice for Preoperative Management of Pheochromocytoma in Pregnancy?
Authors: Bustos Mario , DiCenso Daniela Maria , Ayala Alejandro 
Published: May 2020

Abstract
Pheochromocytoma (PCC) in pregnancy is a very rare condition, with a reported incidence of less than 0.2 per 10.000 pregnancies (1), having fetal and maternal mortality of 50% if untreated (2). Choosing between selective vs. nonselective alpha blockers as preoperative management in pregnancy is controversial.
We report a case of a 39-year-old female having episodes of nervousness, hand tremors, palpitations, diaphoresis, and headaches since 2012; she also had a history of multiple miscarriages and uncontrolled hypertension(HTN) since 2018. In 2019, she was found to have plasma metanephrines 690pg/mL (0-62) and plasma normetanephrine of 3803pg/mL(0-145). Repeat labs showed: plasma metanephrines 2.071pg/mL(0-62), normetanephrine 6.289pg/mL(0-145), norepinephrine 4.268pg/mL(0-874), epinephrine 555pg/mL(0-62). CT abdomen showed a 6.2x5.1x6.4cm left adrenal mass, with 44 Hounsfield units and less than 50% of washout. She was started on Doxazosin 2mg/d, which eventually was increased to 6mg/d with optimal blood pressure (BP) control. After her preoperative workup, she was found to be 7 weeks pregnant. OB-GYN recommended left adrenalectomy before 14 weeks gestation. She had left open adrenalectomy, with normal range postoperative BP, off of antihypertensive medications.
The diagnosis of PCC in pregnancy should be considered in the setting of paroxysmal HTN, with no proteinuria, episodic palpitations, diaphoresis, facial flushing, and orthostatic hypotension. Anterior adrenalectomy early in pregnancy is recommended. The increased intraabdominal pressure, fetal movements, uterine contractions, delivery process, and abdominal surgical intervention can trigger the catecholamine release by the PCC, which could lead to placental abruption and miscarriage; and the rebound hypotension may lead to severe hypoxia, causing fetal demise (2). Definitive preoperative treatment between selective vs non-selective alpha-blockers remains controversial. Phenoxybenzamine, appeared to produce better attenuation of intraoperative HTN, however, it is associated with more maternal intraoperative/postoperative hypotension, and reflexive tachycardia. It crosses the placenta and accumulates in the fetus, increasing the risk of neonatal hypotension and respiratory depression (3,4,5). On the other hand, Doxazosin, can be displaced by high levels of catecholamines, but it is less associated with intraoperative/postoperative hypotension (6,7), with no reports of neonatal hypotension, and respiratory depression. Due to the lack of presynaptic a2-adrenoceptor blockade there is less reflex tachycardia, reducing the use of Beta-blockers (8). Doxazosin seems to be a safe, affordable alternative for preoperative management of PCC in pregnant patients.
MON-303 Giant Growth Hormone Secreting Pituitary Adenomas: A Single Institution Case Series
Authors: Koylu Bahadir , Sendur Suleyman Nahit , Oguz Seda Hanife , Dagdelen Selcuk , Erbas Tomris A 
Published: May 2020

Abstract
The prevalence of growth hormone (GH)-secreting pituitary adenoma is around 11-13% of all pituitary adenomas. Giant GH-secreting pituitary adenomas (≥ 4 cm) are rare tumors, and its prevalence of among acromegalic patients is &lt;5%.
This is a retrospective cohort study including patients with giant GH-secreting pituitary adenomas. The study population consisted of 10 patients (5 M/5 F). The mean age at diagnosis was 33.0±12.9 yrs (11-55 yrs). The mean delay between first symptom onset and diagnosis was 2.9 years. The most frequent symptoms were acral enlargement and facial changes (80%), followed by headache (70%) and visual deterioration (50%). One patient had epilepsy. Amenorrhea was presented in three females but obvious galactorrhea in two. The mean adenoma diameter was 42.6±4.7 mm (40-51 mm) at diagnosis. The vast majority of adenomas presented suprasellar extension (100%) or cavernous sinus invasion (80%). Cystic adenomas accounted for 50%. At presentation, mean GH and IGF-1 levels were 40.0±21.4 ng/mL (14.8-51.0) and 2.62±1.09 x ULN (1.08-3.96), respectively. Six patients presented with PRL cosecretion. At diagnosis maximal tumor diameter was not correlated with GH or IGF-1 levels.
All patients underwent pituitary surgery as first-line treatment. Three cases were treated with an endoscopic approach and four cases with a microscopic approach. Transcranial approach was also employed in three cases. Postoperative mean GH and IGF-1 levels were 14.9±16.1 ng/mL (0.6-51.0) and 2.25.±0.82 x ULN (1.48-3.74), respectively. After first surgery, only one patient had more than 50% reduction in IGF-1 levels. Five patients (50%) underwent repeat surgery on two to three procedures because remission was not achieved. Postoperative somatostatin receptor ligands (SRLs) were used by all patients. Six patients were treated with dopamine agonist in combination with SRL. Six patients (60%) received postoperative radiotherapy.
The mean follow-up period was 12.6±5.3 yrs (4-21 yrs). The mean GH and IGF-1 levels were 1.47±1.54 ng/mL (0.08-5.25) and 0.73±0.44 x ULN (0.08-1.56), respectively at the last visit. Residual adenoma was present at the last MRI in eight patients (mean diameter 9.0±3.6 mm). Panhypopituitarism rose from 10% at baseline to 30% at the last visit. During follow-up, one patient diagnosed breast cancer, while another diagnosed thyroid papillary cancer.
Giant GH-secreting pituitary adenomas can have a clinically aggressive behavior with mass effect. Moreover, treatment in patients with giant GH-secreting pituitary adenoma is complex and multimodal therapy is necessary.
SUN-743 Understanding the Role of Pancreas and Testis Specific lncRNA86 in Estrogen-Dependent Signaling in Breast Cancer
Authors: Ramos Enrique Ivan , Yang Barbara , Choudhari Ramesh , Sanchez-Michael Laura , Sedano Melina , Gadad Shrikanth 
Published: May 2020

Abstract
Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cellular processes, but their roles in breast cancer biology are just beginning to be elucidated. In this study, integration of powerful techniques, RNA-seq data from subcellular fractionated RNA with GRO-seq data has yielded a comprehensive catalog of estrogen-regulated lncRNAs in MCF-7 cells. Analysis of RNA-seq data from samples representing molecular subtypes of breast cancer and normal tissue types, revealed that many lncRNAs (such as lincRNA86) show distinct expression patterns. LincRNA86 shows highest normal expression in pancreas followed by testis in normal human tissues. The hypothesis is lincRNA86 regulate estrogen-dependent signaling in breast cancer. In functional assays, knockdown of lncRNA86 inhibits the growth of ER-positive breast cancer cells. Amplified expression of lncRNA86 in breast cancer correlates with clinical outcome. LncRNA86 have now been fully annotated (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure), and cloned. We are now performing detailed molecular analyses to better understand the underlying mechanisms of action of the lncRNA. We are also currently have experiments underway to view cancer phenotypes: estrogen-dependent tumor growth. Collectively, our preliminary results suggest that lincRNA86 plays a critical role in ERα-dependent pathways.
MON-202 Germline SDHB Exon 1 Deletion Is Associated with Absence of 131I-metaiodobenzylguanidine (MIBG) Uptake in Malignant Paragangliomas
Authors: Petenuci Janaina , Fagundes Gustavo Freitas Cardoso , Motta Flavia Tedesco , Magalhães Aurea Luiza F , Guimaraes Augusto G , Benedetti Anna Flavia Figueredo , Afonso Ana Caroline F , Pereira Maria Adelaide A , Coura-Filho George B , Zerbini Maria Claudia N , Siqueira Sheila , Srougi Victor , Tanno Fabio Y , Chambo Jose Luis , Ferrari Marcela S S , Neto Joao Evangelista Bezerra , Latronico Ana Claudia , Hoff Ana O , Mendonca Berenice Bilharinho , Fragoso Maria Candida B V , Almeida Madson Q 
Published: May 2020

Abstract
Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells. More than 30% of patients with PPGLs have a hereditary predisposition. Malignancy in PPGLs is defined by the presence of local invasion or metastasis in nonchromaffin tissues. Germline SDHB mutations are found in approximately 40% of malignant PPGLs, mainly paragangliomas (PGLs). However, SDHB mutations are not a prognostic factor in malignant PPGLs. To date, no genotype-phenotype correlation has been reported in malignant PPGLs associated with SDHB mutations. Aim: To investigate clinical and imaging features of patients with malignant PGLs harboring germline SDHB exon 1 deletion or splicing site mutation. Methods: We retrospectively evaluated 22 unrelated individuals with malignant PPGLs. Six out of 22 (27%) malignant PPGLs harbored germline SDHB mutations. Three patients had SDHB exon 1 deletion and 3 splicing site mutation (2 with c.201-2A&gt;G and one with c.423 + 1G&gt;A). All SDHB defects were classified as likely pathogenic. Results: In the exon 1 deletion group, 2 patients had abdominal PGLs (one also had a neck PGL) and one had only head and neck PGLs. In the splicing site mutation group, all 3 patients had abdominal PGLs (one also had a neck PGL). Median age at diagnosis was 26 yrs (16 to 45) and 33 yrs (26 to 53) in the exon 1 deletion and splicing mutation groups, respectively. Two patients (one in each group) had metastasis at diagnosis. All 6 patients had bone metastasis, but liver and/or lung metastasis were more frequent in patients with SDHB exon 1 deletion (66 vs. 33%). Interestingly, metastasis from malignant PGLs harboring SDHB splicing site mutations were 131I-metaiodobenzylguanidine (MIBG) avid in all cases, whereas metastatic lesions from malignant PGLs harboring SDHB exon 1 deletion did not present any MIBG uptake on diagnostic imaging studies. Therefore, all 3 patients with SDHB exon 1 deletion were treated with chemotherapy (cyclophosphamide, vincristine and dacarbazine). In contrast, all 3 patients with splicing site mutations have been treated with MIBG therapy. Median follow-up was 87 months (8 to 360 months). Only one patient (exon 1deletion group) died because of disease progression. Conclusion: We first demonstrated here that germline SDHB exon 1 deletion is associated with absence of MIBG uptake in malignant PGLs. This finding needs to be confirmed in an expanded cohort of malignant PPGLs.
MON-373 Low Bone Mineral Density Does Not Equal Osteoporosis: The Finding of XLHR with a Novel Phex Mutation
Authors: Tran Kelvin , Mortensen Michael , Elshimy Ghada , Vinales Karyne Lima , Correa Ricardo Rafael 
Published: May 2020

Abstract
Introduction: X-linked Hypophosphatemic rickets (XLHR) is a rare form of rickets that mainly affects children but, in some cases, it can be missed and not diagnosed until later in life. We present a post-menopausal female that was misdiagnosed with osteoporosis for many years until complete work up was done, and she was found to have osteomalacia due to hypophosphatemia. Clinical case: A 59-year-old female was evaluated following admission to the hospital for a worsening femur fracture on imaging and had received ORIF. She was diagnosed with osteoporosis at the age of 45 and endorses a history of multiple femur fractures from low impact trauma. Despite previous bisphosphonate therapy, she continued to have recurrent fractures.[RC1] She reported no family history of early osteoporosis, but her mother was diagnosed with rickets as a child. Secondary workup for osteoporosis revealed normal 25OH vitamin D, SPEP, TSH, PTH and serum calcium, endomysial antibodies, and 24-hour urine calcium levels. However, the patient had persistently elevated alkaline phosphatase levels (150-200) and low phosphate levels (1.8-2.4). This raised the possibility of Paget’s disease, so a bone scan and lumbar X-ray were obtained which were normal. Given low phosphate levels, fibroblast growth factor (FGF)-23 was obtained and was elevated. This left the differential between tumor-induced osteomalacia (TIO) vs hypophosphatemic rickets. Ga-DOTATE scan and PET scan were negative, so the patient subsequently underwent genetic testing. She was found to have a phosphate regulating endopeptidase homologue (PHEX) gene mutation and was finally diagnosed with XLHR Her PHEX mutation was caused by a novel variant, c.1366 T&gt;C or W456R, which has only been documented once in the literature. The patient was treated with 2 gm per day of phosphate supplementation in divided doses and calcitriol 0.25 mcg once daily which normalized her phosphate and 1,25 vitamin D levels. 1 month later after treatment, she reported significant improvements in bone pain, and her DEXA scans were stable for the following 4 years. Discussion: XLHR is a heterogeneous group of inherited disorders characterized by hypophosphatemia and impaired bone mineralization leading to rickets. It results from mutations affecting the PHEX gene of which more than 300 pathogenic variants have been described. The mutation causes excess FGF-23 which leads to osteomalacia and chronic hypophosphatemia. This condition can be difficult to distinguish from TIO as both present with low phosphate and elevated FGF-23 but can be differentiated with genetic testing. Recognition of the correct diagnosis is prudent to providing correct treatment. The current treatment for XLH is calcitriol and phosphorus replacement. Recently, burosumab was FDA approved in 2018 for treatment in adults.