bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-157 Delayed Diagnosis of Cushings Syndrome: Hiding in Plain Sight!
Authors: Jalil Fatima , Taxel Pamela , Mirza Faryal Sardar 
Published: May 2020

Abstract
BACKGROUND: Endogenous Cushing’s syndrome (CS) is rare, with an incidence of 0.7-2.4/million people/year.1 It should be considered in individuals with diabetes (DM), hypertension (HTN), osteoporosis or electrolyte abnormalities.2 We present a patient with DM2 and persistent hypokalemia for 10 years found to have ACTH-independent Cushing’s disease as the cause of metabolic syndrome. Case: 62 y.o. M admitted with abdominal pain, a history of DM2 (2012) on Metformin 500 mg BID, HTN (2010) and on ramipril 10 mg qd, with chronic lymphedema on furosemide 20 mg qd. He reported 3-inch height loss. On exam, had facial plethora, moon facies, supraclavicular fullness, thick violaceous abdominal striae and kyphosis. Past history was significant for abdominal/leg cellulitis, muscle weakness, difficult to heal wounds, easy bruising and recurrent hospitalizations for hypokalemia, despite being on KCl up to 80 mEq/d for 10 years. Labs showed AM cortisol at 22.6 ug/dL, ACTH &lt;5 pg/mL, 24-hour urine free cortisol of 523 ug/d (normal &lt; 60 ug/d). AM cortisol after 1 mg overnight dexamethasone suppression was 36.8 g/dL, ACTH &lt;5 pg/mL. CT abdomen showed right adrenal nodule, 4.0 x 3.5 cm with density of 22 HU. MRI showed lipid-poor adenoma measuring 3.9 x 3.5 cm, raising concern for adrenocortical malignancy. Patient underwent right adrenalectomy. Pathology was consistent with benign adenoma showing no nuclear pleomorphism, lipid rich cells containing eosnophillic cytoplasm. Mib-1 stain &lt;1% cells and positive inhibin. He was maintained on steroids post op due to concern about adrenal insufficiency. Hypokalemia, DM and lymphedema resolved completely 4 months post op with weight loss of ~30 pounds. HbA1c improved to 5.1%, metformin was stopped and he was maintained on Carvedilol 6.125 mg BID for HTN. He was diagnosed with osteoporosis with T score -4.0 at mean femoral neck, -2.9 for mean total hip with non-diagnostic spine. He had multi-level chronic compression fractures of the mid-thoracic spine. Conclusion: Delayed diagnosis of CS, as occurred in our patient, can result in detrimental consequences such as life threatening electrolyte abnormalities, cardiovascular events, fractures and premature death.1 Identifying CS can be challenging as clinical presentation is variable. 2,3 Early recognition, diagnosis and control of CS is crucial to decrease morbidity and mortality. Our patient demonstrated rapid resolution of DM, hypokalemia and lymphedema after surgery; however, prolonged exposure to endogenous cortisol resulted in compression fractures and osteoporosis requiring follow up treatment. References: 1. Ille I et al, The Multifarious Cushings. Acta Endocrinol.2019 15(2):261-269 2. Reimondo G et al, Lab differentiation of Cushings syndrome. Clin Chim Acta. 2008;388(1-2):5-14 3. Fan L et al, Association of hypokalemia with cortisol and ACTH levels in Cushings disease. Ann N Y Acad Sci. 2019
MON-690 Euglycemic Diabetic Ketoacidosis Associated with SGLT-2 Inhibitors- an Under-recognized Diagnosis
Authors: Chhabra Sarah , Manzano Alex , Garg Neha 
Published: May 2020

Abstract
Background
Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a promising class of oral anti-hyperglycemic agents with mounting evidence of reduced cardiovascular risk and renal failure, in patients with type 2 diabetes mellitus. Recent increase in their use has led to identification of hitherto unknown side effects of these drugs. Euglycemic Diabetic Ketoacidosis (eDKA), found to be associated with SGLT-2i use, is a life-threatening condition and commonly goes unrecognized due to absence of the cardinal sign of hyperglycemia.
Clinical Case
We describe a 47 year old male with history of coronary artery disease and recently diagnosed type 2 diabetes mellitus who presented to our hospital with one week history of nausea, lethargy, progressive fatigue, and shortness of breath. He was diagnosed with type 2 diabetes three weeks prior, with HBA1c of 12%.
His regimen included basal insulin and recent transition to empagliflozin due to severe GI intolerance with metformin use.
On arrival he was noted to be tachycardic with a heart rate of 113/min, afebrile and normotensive. Physical exam was mostly unremarkable except for dry oral mucous membranes. Serum chemistry was consistent with high anion gap metabolic acidosis with bicarbonate of 6.9 mmol/L (21-32 mmol/L), anion gap of 29 mmol/L (10-20 mmol/L), mildly elevated blood glucose of 132 mg/dl (74-106 mg/dl), acute kidney injury with creatinine of 1.47 mg/dl (0.7- 1.3 mg/dl), and a beta hydroxybutyrate level of 82.7 mg/dl (0.20- 5.63 mg/dl). Urine analysis showed ketonuria. This was consistent with a clinical and biochemical diagnosis of eDKA. He was treated with IV D5%NS-20mEq/L KCL and an insulin drip. Upon resolution of his acidosis and normalization of the anion gap he was switched to subcutaneous Insulin Glargine and Lispro. Empagliflozin was held as it was thought to be contributing to the diagnosis of eDKA.
Conclusion
Our case yet again illustrates the importance of recognition of EDKA to aid prompt management, especially with the rising popularity of SGLT-2 inhibitors. It is also important to educate patients about this condition, mostly notable in the first two months of starting the medication, to recognize the concerning symptoms and precipitating factors like dehydration, improper insulin dosing, low calorie diet, alcohol, infection, surgery. An acceptable alternative to SGLT-2i can be glucagon like peptide receptor (GLP- 1) agonists, also associated with good cardiovascular outcomes.
SUN-632 The Impact of Vitamin D Deficiency on Pregnancy in Type 1 Diabetes
Authors: Kolpakova Evgenia , Ibragimova Liudmila , Derevyanko Olga , Ragimov Magomed , Bostanova Fatima , Nikankina Larisa , Nikonova Tatiana 
Published: May 2020

Abstract
Vitamin D deficiency during pregnancy may not only impair maternal skeletal preservation and fetal skeletal formation but also influence fetal “imprinting” that may affect chronic disease susceptibility soon after birth as well as later in life.
Vitamin D deficiency has been linked to multiple adverse perinatal outcomes in pregnancy including; pre-eclampsia, gestational diabetes, low birth weight, bacterial vaginosis, pre-term delivery and caesarean section. Aim: to assess 25-hydroxy vitamin D (25OHD) concentrations in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and also foetal (cord blood) 25OHD concentrations and to examine relationships between these. The second aim of the study to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c) throughout pregnancy. Materials and methods: This was an observational study of 42 pregnant controls without diabetes and 39 pregnant women with T1DM. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). HbA1c was measured serially throughout the pregnancy. Control and T1DM groups were not significantly different in age or number of previous miscarriages. As expected, the T1DM group exhibited significantly higher HbA1c levels, and also had significantly increased incidence of preeclampsia (2 of 42 cases (4,8%) in control group and 5 of 39 cases in T1DM group (12,8%)) (p= 0,03). Delivery gestational age was significantly lower for babies born to mothers with T1DM (39,6±1,4 weeks in control group and 37,6±2,1 in T1DM group (p= 0,001).
Vitamin D deficiency, defined as 25OHD levels,25 nmol/L, was apparent in both the control and the T1DM groups across the entire pregnancy. Greater than 90% of pregnant women were classified as insufficient at each time-point, regardless of whether they had T1DM or not. This meant that 10% of this pregnant population were at a sufficient level at some point throughout pregnancy. Similar to maternal vitamin D levels, the neonates had a high incidence of 25OHD deficiency at birth. Also were shown correlations between cord blood and maternal vitamin D. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group. Conclusions: in T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery; maternal vitamin D levels exhibit a significant negative relationship with HbA1c levels, supporting a potential role for this vitamin in maintaining glycaemic control; larger studies investigating whether low vitamin D levels are a risk factor for preterm delivery and preeclampsia in women with diabetes are needed.
OR26-04 Immediate Post-Operative Insulin Requirements May Predict Metabolic Outcome After Total Pancreatectomy and Islet Autologous Cell Transplant (TPIAT)
Authors: Verma Neha , Rajab Amer , Buss Jill , Lara Luis , Porter Kyle , Hart Philip , Conwell Darwin , Washburn W Kenneth , Black Sylvester , Kuntz Kristin , Meng Shumei 
Published: May 2020

Abstract
Immediate Post-Operative Insulin Requirements may Predict Metabolic Outcome after Total Pancreatectomy and Islet Autologous Cell Transplant (TPIAT) Introduction: Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Patients with CP experience abdominal pain, which in some instances can be refractory to medical and endoscopic intervention. Total pancreatectomy and islet auto transplantation (TPIAT) is a treatment option however predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield as well as post-TPIAT glucose management data to further understand their relationship.Methods:A total of 13 TPIAT subjects were included who underwent beta cell function assessment via intravenous glucose tolerance tests and oral mixed meal tolerance tests. Islet yield, glucose level and insulin requirement for 72 hours postoperatively were collected. In addition, their glucose control and insulin requirements at 3, 6 and 12-month post TPIAT were analyzed.Results:The median age was 45 years with median duration of CP for 5 years. The main cause of CP was idiopathic. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median post-operative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour post operatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6 and 12 month showed a positive correlation. Despite the new finding of inverse correlation of islet yield with long-term insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies.Conclusion: The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long term insulin management following TPIAT. This observation may identify a high risk group of patients in need of more intensive diabetes education and treatment prior to hospital discharge.
SUN-355 Associations of Trabecular Bone Score and Bone Mineral Density with Cardiorespiratory Fitness and Body Composition in Men with and Without Paraplegia
Authors: Usuga Daniela , McMillan David W , Jacobs Kevin A , Nash Mark S , Valderrabano Rodrigo J 
Published: May 2020

Abstract
Introduction: Following spinal cord injury (SCI) lower extremity bone mineral density (BMD) losses are as high as 40% due to mechanical unloading and autonomic dysfunction. While lumbar spine (LS) BMD appears to be relatively spared, evidence suggests BMD by dual-energy radiographic absorptiometry (DXA) may overlook bone pathology in this region. Trabecular Bone Score (TBS), representative of bone microarchitecture, may be a more informative measurement of LS pathology in SCI. Our objective was to determine differences in BMD and TBS within the LS in humans with and without SCI. Correlation of fitness and body composition measures with TBS and BMD were also explored to determine their role in bone health after SCI.
Methods: Seven male participants with paraplegia (level T3 – T7) were recruited through The Miami Project to Cure Paralysis, and 6 males without SCI were recruited from local advertisement. DXA scans of the lumbar spine and whole body were performed using Hologic Discovery A densitometer. TBS score (unitless) was derived from L1-L4 scans using TBS iNsight software v3.0.2. A graded arm exercise test directly measured cardiorespiratory fitness (VO2peak) for all subjects. An independent samples t-test determined between-group differences in LS BMD and TBS. Pearson correlation analysis investigated within-group relations among LS BMD, TBS and VO2peak (ml/kg/min), weight (kg), total body fat (%), and visceral adipose tissue (estimated VAT mass(g)).
Results: In SCI, the mean duration of injury was 8.6 years. Mean LS BMD was not different (p=.47) between non-injured (1.10 ±0.11 g/cm2) and SCI (1.10 ±0.13 g/cm2) groups. However, mean TBS score was different (p=.053) between non-injured (1.55±0.09) and SCI (1.47±0.07) groups. In non-injured, VO2peak was correlated with LS BMD (r=.356) and TBS (r=.244). In SCI, VO2peak was correlated with LS BMD (r=.111) and TBS (r=.822). In non-injured, TBS was correlated with body mass (r=.244), total body fat (%) (r=.382), and visceral adipose tissue (r=.361). In SCI, negative correlations were observed; TBS was correlated with body mass (r= -.255), total body fat (%) (r= -.474), and visceral adipose tissue (r= -.513). LS BMD was positively correlated with body mass, total body fat (%) and visceral adipose tissue in both non-injured and SCI groups.
Conclusion: Men with and without SCI displayed similar BMD but differed in TBS at the LS. Correlations with measures of fitness and body composition were similar for LS BMD but discordant for TBS between non-injured and SCI groups. The data suggest changes in the relationships between cardiorespiratory fitness, metabolism and bone quality in SCI. TBS may capture alterations in bone microarchitecture at the spine after SCI that are undetected by conventional DXA.
MON-006 Progesterone Receptor Expression in Endometrial Biopsies After 12 Weeks of Exposure to A 4-µg E2 Softgel Vaginal Insert or Placebo
Authors: Simon James A , Liu James H , Archer David F , Komm Barry S , Bernick Brian , Mirkin Sebastian 
Published: May 2020

Abstract
The softgel, vaginal 17β-estradiol (E2) insert (TX-004HR) significantly improved the maturation index of the vaginal epithelium, dyspareunia and vaginal dryness in menopausal women with vulvar and vaginal atrophy (VVA) and moderate to severe dyspareunia, without histological changes to the endometrium (Constantine G et al, Menopause 2017;24:409-416). The 4-μg and 10-μg E2 doses were FDA approved as Imvexxy® (TherapeuticsMD, Boca Raton, FL), for the treatment of moderate to severe dyspareunia, a symptom of VVA, due to menopause. The progesterone receptor (PR) is an estrogen-regulated gene with expression that is very sensitive to E2 exposure (Xiao CW and Goff AK, J Reprod Fertil.1999;115:101-109). Endometrial PR expression in the biopsies of women using the softgel vaginal 4-µg E2 insert was used as a marker of E2 exposure to determine whether sufficient E2 applied with the vaginal insert reaches the endometrium to upregulate PR expression. Our hypothesis posits that there would be insufficient E2 from the 4-µg E2 insert to stimulate an increase in endometrial PR expression.
In this post hoc analysis of the REJOICE trial, endometrial biopsies from 25 women who had a normal baseline biopsy, an on-therapy biopsy after study day 70, and tissue readings from all pathologists were randomly selected from the 4-µg E2 vaginal insert and placebo groups. Endometrial tissue sections were stained to visualize PR expression using PgR1294 (Agilent; Santa Clara, CA). Cell staining was quantified using a trainable feature-recognition algorithm and mean expression levels between baseline and week 12 were analyzed by 2-sided t-tests.
Acceptable PR expression results were available for 22 women in the 4-µg E2 group (three had insufficient tissue for analysis) and 25 women in the placebo group. For the 4-µg E2 group, mean ± SD (pmol/mg) PR expression was 0.455 ± 0.203 at baseline and 0.506 ± 0.226 at week 12. For the placebo group, mean PR expression was 0.579 ± 0.196 at baseline and 0.563 ± 0.213 at week 12. Mean PR expression levels at baseline and week 12 were not significantly different from each other within the 4-µg E2 (P=0.438) or placebo (P=0.783) group.
No meaningful difference in endometrial PR expression was observed with the vaginal 4-µg E2 insert at week 12. These data support our hypothesis and the assertion that low-dose, local vaginal E2 exposure with the insert placed in the lower part of the vagina, does not pose an endometrial safety issue in postmenopausal women.
SAT-288 Pituitary Developmental Defects Caused by Haploinsufficiency for the Transcription Factor SIX3 Are Worsened by POU1F1 Deficiency
Authors: Brinkmeier Michelle , Camper Sally Ann 
Published: May 2020

Abstract
Advances in genomic technologies are revolutionizing the practice of medicine by delivering molecular diagnoses that can be informative for prognosis and treatment of genetic disorders. Most of the known genetic causes of multiple pituitary hormone deficiency have been investigated as monogenic disorders. It can be challenging to predict clinical features from genetic data, as loss of function mutations in some genes can present with a spectrum of phenotypes ranging from craniofacial abnormalities, intellectual disability, and neurosensory and neuroendocrine defects to pituitary hormone deficiency with no other abnormalities. Although maternal exposures could be contributing factors, the contribution of rare, deleterious variation in other genes is a likely contributor. In humans, loss of function mutations in the transcription factor SIX3 cause variable, autosomal dominant holoprosencephaly with incomplete penetrance, and mouse models recapitulate some of the clinical features. Because Six3 and Pou1f1 gene expression patterns overlap in pituitary development, we hypothesized that doubly heterozygous mice (Six3+/-; Pou1f1+/dw) might have pituitary anomalies not present in singly heterozygous mice. We intercrossed Six3+/- and Pou1f1+/dw mice to produce doubly heterozygous animals. At e11.5, both Six3+/- and Six3+/-; Pou1f1+/dw exhibited abnormal morphology of the developing infundibulum and Rathke’s pouch, although ventral diencephalon expression of Tle4, Fgf10, and Nkx2.1 appeared normal. Both newborn Six3+/- and Six3+/-; Pou1f1+/dw littermates had abnormal pituitary gland morphology that resembled that of Aes-/-. AES is a co-repressor that interacts with SIX3. Specification of vasopressin neurons and anterior lobe hormone cell types appeared normal. Mice of all genotypes were born in expected Mendelian ratios (N=144, p=0.49), and there were no significant differences in body weight at 3 wks. A portion of the Six3+/- and doubly heterozygous mice developed hydrocephalus, exhibited failure to thrive, and died (6-9% of N=82, 85, respectively). At 6 wks, 25% (N=61) of the Six3+/-; Pou1f1+/dw animals exhibited striking pituitary dysmorphology in which the rostral aspect of the pituitary penetrated the palate. This was not observed in single heterozygotes. These results reveal that haploinsufficiency for Six3 affects Rathke’s pouch formation, resulting in pituitary gland dysmorphology in and around the stem cell niche. A significant portion of the Six3+/-; Pou1f1+/dw doubly heterozygous mice have a more pronounced pituitary phenotype than Six3+/-, supporting the possibility of digenic pituitary disease and highlighting phenotypic variability. Genetically engineered mice provide an excellent tool for assessing the possibility of gene-gene interactions that could enhance the severity of hypopituitarism and associated craniofacial development.
SUN-346 A Natural Antibody Against Oxidized Phospholipids Attenuates Age-Related Bone Loss and Prevents Age-Related Glucose Intolerance in Mice
Authors: Palmieri Michela , Teenamol Joseph , Gomez-acevedo Horacio , Witztum Joseph Lee , Manolagas Stavros C , Ambrogini Elena 
Published: May 2020

Abstract
Lipid peroxidation produces oxidized phospholipids (OxPL) such as oxidized phosphatidylcholine. These compounds react with amino groups of proteins and lipids to form adducts called oxidation specific epitopes (OSEs), which are proinflammatory moieties present on oxidized low density lipoproteins and on apoptotic cells and, unless removed, cause extensive cell damage. Natural antibodies (NAb) produced by B-1 lymphocytes, bind OxPL and prevent their inflammatory activity. E06 is a NAb that recognizes the phosphocholine moiety of OxPL. We previously showed that transgenic expression of a single chain (scFv) form of the antigen-binding domain of E06 IgM (E06-scFv) increases cancellous and cortical bone mass in both male and female mice by increasing bone formation. Age-related bone loss is characterized by a decline in osteoblast number and bone formation, associated with increased oxidative stress and lipid peroxidation. These findings, together with the evidence that serum anti-OxPL IgM titers decrease with age, suggest that increased OxPL formation and decreased anti-OxPL antibodies may contribute to age-related bone loss. Like humans, mice exhibit an age-dependent worsening in glucose tolerance, mainly due to alteration in body composition and increased fat tissue. Chronic low grade inflammation and oxidative stress are associated with development of diabetes mellitus and B-1 lymphocytes have been shown to be protective against obesity associated inflammation, glucose intolerance, and insulin resistance. We tested the hypothesis that overexpression of E06-scFv could attenuate age-related bone loss and glucose intolerance. Serial BMD measurements by DXA of both female and male C57BL/6 E06-scFv transgenic mice (and their WT littermates) up to 22 and 24 months, respectively, showed that E06-scFv attenuated age-related bone loss at the spine and femur in both sexes. As revealed by microCT analysis, this effect was due to the attenuation of the age-associated decline in cancellous bone in both sexes. Additionally, both male and female E06-scFv transgenic mice accumulated less fat mass than WT littermates during aging. Intraperitoneal glucose tolerance test, at 15 months of age, revealed that glucose tolerance was greater in both male and female E06-ScFv mice than in respective WT littermates and did not differ from the glucose tolerance of young mice, indicating that E06-scFv improves glucose metabolism. These data suggest that OxPL impair both age-related bone loss and age-related glucose intolerance. Therefore, targeting OxPL with a neutralizing antibody such as E06, represents a prototypic therapeutic intervention that may simultaneously ameliorate important age-associated diseases.