bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-343 Prevalence and Incidence of Hypomagnesemia and Hypermagnesemia in Medical Settings
Authors: Catalano Antonino , Bellone Federica , Morabito Nunziata , Chila Diego , Loddo Saverio , Corica Francesco , Benvenga Salvatore 
Published: May 2020

Abstract
Electrolytes disturbances are commonly observed in clinical practice. However, magnesium (Mg) disorders are often poorly considered. Our primary aim was to update the prevalence and the incidence of hypomagnesemia and hypermagnesemia in a real-life scenario. The secondary aim was to investigate the association of Mg disturbances with age and gender. Data from patients whose Mg serum levels were measured between January 2015 and December 2017 at our University Hospital were recorded. Hypomagnesemia was defined by Mg levels &lt;1.5 mg/dL and hypermagnesemia by levels&gt; 3.8 mg/dL. Hypo and hypermagnesemia cases were considered according to age, gender, year of observation and setting of subjects including outpatients and inpatients. In particular, inpatients were recruited from a total of 25 Hospital Divisions (i.e. Cardiology, Endocrinology, Geriatrics, Hematology, Intensive Care, Internal Medicine, Infectious Disease, Nephrology, Neonatal Intensive Care, Neurology, Neuropsychiatry, Neuroradiology, Oncology, Pulmonology, Pediatrics, Psychiatry, Rheumatology and Surgical Area that included 8 Units). Over the observation period, we recognized 12,696 patients whose Mg levels were checked. Prevalences of hypomagnesemia and hypermagnesemia were 8.43% (n=1071) and 1.78% (n=226) respectively. Hypomagnesemia was encountered more frequently in female [53.3% (n=560)] rather than in male patients [47.7 % (n=511)] (χ2= 4.03, p&lt;0.045) and was significantly influenced by age: the higher prevalence of hypomagnesemia was found in patients over 65 yr. [59.01% (n=632)], whereas a lower prevalence was detected in the other age groups, specifically in 9.52 % (n=102) of patients aged 0-18 yr. and in 31.46 % (n=337) of patients between 19 and 65 yr. (χ2= 592.64; p&lt;0.0001). Incidence of hypomagnesemia decreased over time with a borderline significance only in subjects over 65 yr. (r=-0.99; p=0.07). Geriatrics, Oncology and Intensive Care Division showed the highest incidences of hypomagnesemia. The hypermagnesemia prevalence was observed higher in outpatients in comparison with inpatients from any other Hospital Division and the hypermagnesemia incidence did not significantly change over time (r=0.96; p=0.16). Mg disorders, mainly hypomagnesemia, are quite common in clinical practice particularly in older hospitalized patients. Among the other electrolytes’ disturbances, Mg disorders, because of life-threatening significances, may be checked and corrected.
SUN-164 Adrenal Crisis in Early Pregnancy
Authors: Bello Jenny Carolina , Chen Xiaolei , Chen Kenneth K 
Published: May 2020

Abstract
Nausea and vomiting are common symptoms in pregnancy, ranging from occasional nausea to fulminant and intractable vomiting. Many underlying metabolic disorders can mimic this, primary adrenal insufficiency (PAI) being one of them. Here, we present a case of adrenal insufficiency early in pregnancy.
A 28 year old lady G1P0 at 8 weeks of gestations, with a past medical history of Grave’s Disease, presented to our hospital on 3 occasions over one week with severe intractable nausea and vomiting. On prior visits, she had received intravenous fluids and discharged home. Laboratory work-up was ordered on the third visit and she was found to have severe hyponatremia with level of 111mMol/L. TSH and FT4 levels were both within the reference range. AM cortisol level was low at 2.3mcg/dL. ACTH and renin were both significantly elevated confirming diagnosis of PAI. Intravenous hydrocortisone was commenced immediately with rapid resolution of her symptoms and correction of her hyponatremia. She was followed at the endocrinology clinic, with appropriate up-titration of glucocorticoid and mineralocorticoid doses throughout her pregnancy.
Diagnosis of PAI is usually established prior to pregnancy. Presentation during pregnancy is not common, but it should be considered as a differential diagnosis when symptoms are out of proportion to the gestational status. Normal pregnancy is accompanied by progressive increase in circulating CRH and ACTH, increasing the levels of free cortisol as early as 7 weeks of gestation, rising up to 20-fold by the end of pregnancy. These physiologic changes could explain early presentation of adrenal crisis given insufficient glucocorticoid production. A delay in diagnosis and treatment increases the risk of maternal and fetal morbidity and mortality significantly.
Management of PAI during pregnancy can be challenging as there are no established guidelines and they have mainly been based on observational studies (1). The appropriate selection and dose of the glucocorticoid is important for the treatment of PAI to minimize adverse effects on mother and baby (2). At the time of active labor and delivery, stress doses of glucocorticoids need to be administered to prevent adrenal crisis (3).
In conclusion, early diagnosis and appropriate management of PAI during pregnancy is necessary to sustain a healthy pregnancy.
Bibliography
1 Husebye ES, Allolio B, Arlt W, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104– 15.
2 Bandoli G, Palmsten K, Forbess C, et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017; 43(3): 489–502
3 Chen K, Powrie R. Approach to the use of Glucocorticoids in Pregnancy for Nonobstetric Indications. de Swiet’s Medical Disorders in Obstetric Practice: Fifth Edition. 736-741.
SAT-652 Increased Fibroblast Growth Factor 21 Protein Expression via in Vivo Delivery of a Liver-Specific Expression Plasmid
Authors: Girer Nathaniel , Rontoyanni Victoria , Porter Craig , Elferink Cornelis 
Published: May 2020

Abstract
Fibroblast growth factor 21 (FGF21) is an important liver-secreted hormone that activates thermogenesis in white and brown fat deposits. In various models of obesity, FGF21 administration consistently facilitates weight loss and improved metabolic function. Several FGF21 variants, which have been engineered to improve protein stability and solubility in solutions containing preservatives, are currently in human clinical trials. In addition, in vivo FGF21 gene therapy using viral vector is being explored as an alternative therapeutic approach. In this study, we present a simpler method of in vivo FGF21 gene therapy, in which liver-specific delivery of an unpackaged plasmid construct expressing an HA-tagged FGF21 protein increases de novo hepatic FGF21 production and secretion in mice. Our data show that FGF21 protein expression can be successfully restored into the livers of FGF21 conditional knockout mice for at least two weeks after a single tail vein injection with the expression plasmid, and that the HA-tagged protein is secreted and readily detectable in serum. In wild-type C57BL6/J mice, in vivo plasmid delivery significantly increased hepatic FGF21 protein 2.3-fold after two weeks, and was associated with reduced body mass and a 14% reduction in fasting serum glucose. In addition, elevated hepatic FGF21 levels correlated with a 27% decrease in the ratio of fat to body mass, visibly smaller subcutaneous and visceral white fat adipocytes, and a 3.3-fold increase in uncoupling protein 1-dependent mitochondrial respiration in the white fat. Together, these data suggest that in vivo plasmid delivery may potentially be an effective strategy for promoting hepatic FGF21 expression in models of obesity. We are currently testing this hypothesis with experiments in high-fat diet-challenged mice.
SUN-620 Gender Difference in the Outcome of Patients with Diabetes Admitted for Hyperosmolar Hyperglycemia. from the National Inpatient Sample
Authors: Ahmed Fatima , Abugroun Ashraf , Elhassan Manar , Seyoum Berhane 
Published: May 2020

Abstract
Objective: There is paucity of literature on the impact of gender on outcomes of hyperosmolar hyperglycemic state (HHS) among adult patients with diabetes. The aim of this study was to evaluate the effect of gender on the outcome of these patients. Methodology: The National Inpatient Sample (NIS) was queried for all patients who were admitted with a diagnosis of hyperosmolar hyperglycemic state (HHS) during the years 2005-2014. The primary outcomes of the study were all-cause mortality, acute myocardial infarction (MI), and acute stroke. The secondary outcomes were acute kidney injury (AKI), rhabdomyolysis, acute respiratory failure (ARF), need for mechanical ventilation (MV), length of stay (LOS), and total cost of stay. Results: Overall, 188,725 patients were admitted for HHS. Mean age of males was 53.7, standard error of the mean (SEM: 0.13), and of females was 58.5 (SEM: 0.15), p&lt;0.001. Females were (43.9%), Caucasians were 37.4% while African Americans were 35.2%. Total mortality was 1.1%, MI was 1.3% and stroke was 1.1%. Most common secondary outcome was AKI seen in 31.3% followed by ARF seen in 2.9% of total. The mean cost was 7887 $ (SEM: 84.6) and mean LOS was 4.1 days (SEM: 0.03). Both males and females had equivalent rates of mortality, stroke, ARF and need for mechanical ventilation. Compared to males, females had significantly higher risk for MI 1.6% vs 1.1%, p&lt;0.001, lower risk for AKI 29.3% vs 32.9%, p&lt;0.001, lower risk for rhabdomyolysis 1.1% vs 2%, p&lt;0.001 and higher LOS 4.3 vs 3.9 days, p&lt;0..01 and higher total costs 8165.6 $ vs 7669.3 $, p &lt; 0.001. On multivariable analysis, female gender was independently predictive for higher risk for MI with adjusted odds ratio (aOR) 1.34 [95%CI: 1.08-1.67] p=0.01 and lower risk for rhabdomyolysis with aOR 0.52 [95%CI: 0.42-0.63] p&lt;0.001 and lower risk for AKI with aOR 0.74 [95%CI: 0.7-0.78] p&lt;0.001. In addition, female gender correlated with higher cost and length of stay. Conclusion: Females with hyperosmolar hyperglycemic state are at higher risk for MI and lower risk for AKI and rhabdomyolysis.
SAT-389 Clinical and Biochemical Characterization of Risk Factors for Vertebral Fractures in Patients with Hypoparathyroidism
Authors: Formenti Anna Maria , Filippo Luigi Di , Allora Agnese , Giubbini Raffaele , Giustina Andrea 
Published: May 2020

Abstract
Background: Persistent hypoparathyroidism (PH) is a rare disease due to an impaired secretion of PTH, mostly occurring as a complication of total thyroidectomy. Calcium and calcitriol are currently the most common and inexpensive therapies, although not all the patients easily achieve control of the disease. Recently, our group has reported that BMI at diagnosis can predict calcitriol resistance in PH. Very few studies have been performed with fractures as primary endpoint in hypoparathyroidism, and we still not know if PH could be predisposing to an increased risk of morphometric fractures and possible clinical and biochemical predicting factors. Patients and methods: To that end we retrospectively evaluated the anthropometric, biochemical and fracture characteristics in 71 consecutive patients with PH (F/M= 62/9; median age 58.7 yrs, range: 29-87; 67 with post-surgical PH and 4 with autoimmune PH). All patients were hypoparathyroid from at least one year (median duration of disease: 9 yrs., range: 1-41) and were under standard treatment with calcium and active vitamin D analogs (calcitriol). For each patient anthropometric data (BMI=kg/m2; N= Normal weight patients &lt;25; OO= Obese and overweight patients with BMI &gt; 25) were collected, as well as biochemical parameters, such as calcium (mg/dl) and 25 OH vitamin D (25OHD expressed as ng/ml). We considered well controlled (C) patients with calcium between 8.2 and 9.2 mg/dl and not controlled (NC) under 8.2 or above 9.2 mg/dl. Vertebral fractures (VF) were assessed by a quantitative morphometric approach by using images provided by DXA and classified according to Genant classification. Results: Thirteen out of 71 patients (18%) were fractured. We showed a positive linear correlation in the overall population between BMI and calcitriol intake (p=0.006, CI 95% [1.2-6.9]) while no significant difference in prevalence of VF in OO vs N group (8/40 vs 5/31, p=0.76) was found. However, almost half (6/13, 45%) of patients with VF were OO NC. Moreover, 86% of NC vs only 30% of C fractured patients (6/7 vs 2/6) were OO Discussion: We report a high prevalence of VF in hypoparathyroidism. Moreover, we confirm that increased BMI is associated with higher needs of calcitriol to obtain calcium control. Interestingly, our data suggest for the first time that OO hypoparathyroid patients with NC disease are those at highest risk of fracture. Therefore, in this subset of patients a more intensive and proactive biochemical and bone monitoring should be adviced if these results will be confirmed in larger studies.
OR05-01 Small Heterodimer Partner Modulates Antigen Presenting Myeloid Cells to Impair Regulatory T Cell Expansion, Promoting Anti-Tumor Immunity in Models of Breast Cancer
Authors: Shahoei Sayyed Hamed , Nelson Adam T , Henn Madeline A , Mathews Ashley E , Chen Joy J , Vembar Varsha , Vardanyan Anna , Ma Liqian , Wang Yu , Apetoh Lionel , Nelson Erik Russell 
Published: May 2020

Abstract
Immune checkpoint blockade has had underwhelming responses in breast cancer, in part due to the highly immune suppressive microenvironment. As a result, breast cancer continues to be the second most common cancer-related mortality amongst women, providing strong rationale for the development of new therapeutic approaches. Elevated circulating cholesterol is a poor prognostic, while breast cancer patients taking cholesterol-lowering drugs display increased time to recurrence. We and others have previously demonstrated that cholesterol metabolites mediate these effects by promoting breast cancer growth and metastasis, in part by suppressing the immune system. Therefore, given the demonstrated importance of cholesterol and its metabolites in breast cancer pathophysiology and immunology, we hypothesized that proteins involved in the regulation of cholesterol homeostasis would influence cancer progression. Through informatics analysis of breast tumors, we found that elevated expression of Small Heterodimer Partner (SHP; NR0B2) was a favorable prognostic. Antigen presenting cells such as macrophages and dendritic cells were found to express SHP, and manipulation of SHP altered the expression of genes involved in cross-talk with T cells. Intriguingly, when activated T cells were co-cultured with macrophages overexpressing SHP, there was a decrease in the expansion of regulatory T cells (Tregs) and vice versa in the absence of SHP. Adoptive transfer studies confirmed that loss of SHP resulted in immune suppressive Tregs. We hypothesized that myeloid cell-expressed SHP would promote immune surveillance and tumor clearance. In support of this hypothesis, tumors in the MMTV-PyMT model of mammary cancer grew at an accelerated rate in SHP-knockout mice. Tumors from these mice had significantly more Tregs and fewer effector T cells. Furthermore, orthotopic mammary tumor grafts grew at an increased rate in mice lacking SHP expression in myeloid cells (SHPfl/fl;LysMCre), compared to controls. A small molecule agonist of SHP impaired primary and metastatic tumor growth, and significantly enhanced the efficacy of immune checkpoint blockade in murine models of mammary cancer. Therefore, SHP represents a potential target to decrease suppressive Tregs, thereby allowing for immune-clearance of tumors.
SAT-258 Surprising Transformation of a Microprolactinoma to a Macroprolactinoma
Authors: Athonvarangkul Diana , Hosier Hillary Wyeth , Wojeck Brian , Inzucchi Silvio E 
Published: May 2020

Abstract
Background: Microprolactinomas are typically benign tumors that rarely become macroprolactinomas. We present a rare case of a microprolactinoma that, after discontinuation of dopamine agonist (DA) therapy, transformed into a macroprolactinoma over a period of 6 years.Clinical Case: A 16-year-old woman initially presented for evaluation of galactorrhea without menstrual irregularities and was found to have elevated prolactin (68 ng/ml, normal range: 0-20), and a 4 mm pituitary microadenoma on MRI imaging. The patient was otherwise asymptomatic and other pituitary hormone levels were normal. She was treated with DA therapy (cabergoline 0.50 mg/week) which normalized her PRL level and improved but did not completely resolve the galactorrhea. She was then lost to follow up for 6 years. During that time, she discontinued cabergoline, but was still able to conceive, delivering a healthy baby after 2 years and breastfed briefly. She re-presented to her gynecologist 4 years after delivery for galactorrhea and secondary amenorrhea, both persistent since childbirth. Re-evaluation at that time revealed a much higher PRL level (432 ng/ml) and significant interval growth of the previous microadenoma to a 2.6 cm macroadenoma, now with extension into the left cavernous sinus, suprasellar cistern, with mass effect on the optic chiasm. The patient was retreated with cabergoline up to 3 mg/week, with a near-normal PRL level being achieved at 9 months (28 ng/ml). Repeat MRI revealed modest decrease of the adenoma to 2.4 cm. Galactorrhea resolved with reduction in PRL. However, amenorrhea persisted. Estradiol (30 pg/mL, 19-357 pg/mL) was low normal with normal withdrawal bleeding to medroxyprogesterone (MPA) challenge indicating reasonable estrogenization. She was treated with MPA to achieve regular cyclic bleeding every 3 months. Conclusion: This is an unusual case demonstrating significant growth of a microprolactinoma, which is typically a stable/indolent neoplasm, to a macroprolactinoma with invasive features. Previous studies of untreated microprolactinomas have shown that they undergo only subtle to minimal growth over 3 to 6 years and none transformed to a macroprolactinoma despite significant rises in PRL levels. In this clinical case, given the 6 intervening years that had elapsed in between MRIs, we cannot determine whether this represented moderate, progressive growth during that period after the discontinuation of DA therapy or whether the tumor had grown during pregnancy with its known stimulatory effects from hyperestrogenemia. The patient will require close follow-up to ensure ongoing shrinkage or at least stability of the adenoma and ongoing control of her hyperprolactinemia.References:1. Fertility and sterility39, 753-760 (1983). 2. Dietemann, J.L et al. Neuroradiology25, 133-138 (1983). 3. Garcia, M.M et al. Journal of endocrinological investigation18, 450-455 (1995).
OR33-03 Congenital Leptin Deficiency: Clinical Insights from the First Reported US Cases
Authors: Torchen Laura C , Hakamy Beth , Gordon Leo I , Marsh Erica E , Yaseen Nabeel R , Neff Lisa M 
Published: May 2020

Abstract
Background: Congenital leptin deficiency (CLD) is a rare autosomal recessive form of monogenic obesity caused by loss-of-function mutations in the leptin gene. Targeted therapy is available in the form of recombinant human leptin (metreleptin). Previous case series have reported dramatic weight loss and metabolic improvements with treatment, but metreleptin’s only FDA-approved indication is acquired generalized lipodystrophy (AGL). Metreleptin has a black box warning for risk of T-cell lymphoma, which has been reported in AGL patients, both treated and untreated with metreleptin.
Clinical Case: Two sisters ages 18 yrs (sister A; BMI 45.2 kg/m2) and 20 yrs (sister B; 45.0 kg/m2) were referred for evaluation of obesity. They are of Pakistani origin with a family history of consanguinity. Birth weight was normal, but hyperphagia and excessive weight gain developed by age 3 months. They had been seen by endocrinologists, obesity specialists, and a geneticist during childhood but work-up for monogenic obesity was not pursued. They were treated with combination OCPs in adolescence due to primary amenorrhea and hypogonadotropic hypogonadism. Sister A was diagnosed with type 2 diabetes at age 15 years. Sister B had comorbidities of hydrocephalus s/p VP shunt, developmental delay, hyponatremia, autoimmune thyroid disease, growth hormone deficiency, and prediabetes. At the time of their present evaluation, serum leptin levels were obtained and were undetectable in both sisters. After discontinuing OCPs, testing confirmed hypogonadotropic hypogonadism. Both patients were homozygous for the pathogenic variant c398delG in exon 3 of the leptin gene (LEP), which causes a frameshift/premature stop codon. On MR elastography performed for hepatic steatosis, sister B had an incidental finding of axillary lymphadenopathy. Surgical biopsy and staging work-up confirmed diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (a B cell lymphoma), Stage II disease. She was treated with R-ABVD with adjuvant radiation and achieved clinical remission, prior to treatment with metreleptin. The patients were enrolled in an observational treatment protocol, and responses to metreleptin therapy will be reported in future.
Conclusion: To our knowledge, these are the first cases of CLD diagnosed in the U. S. In previous reports, CLD and other monogenic obesity disorders were prevalent among children with severe obesity in a consanguineous Pakistani population. Leptin deficiency should be considered in all patients with early onset obesity and hypothalamic amenorrhea. Furthermore, to our knowledge, this is the first report of lymphoma in a patient with CLD, occurring prior to any treatment with metreleptin. The risk for lymphoma associated with metreleptin may relate to preexisting autoimmune disease or immunologic abnormalities related to leptin deficiency rather than medication adverse effect.