bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-349 Left Hip Pseudofracture in a Patient with Refractory Paget Disease of the Bone
Authors: Gastelum Alheli Arce , Pinjala Anusha , Maraqa Sima , Block Megan , Zena Mohsen 
Published: May 2020

Abstract
Background
Paget’s disease of the Bone (PDB) is a benign condition caused by focal abnormal bone remodeling. It is largely asymptomatic and is often discovered incidentally while investigating an elevated alkaline phosphatase (ALP) or imaging studies.
Diagnosis relies on biochemical screening, ALP, as a first line test. X-rays and radionuclide scans can assist in determining the extent of disease. Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB.
Clinical case
A 51-year-old, non-verbal female presented to the Endocrinology office with her legal guardian for a follow-up regarding Paget’s disease of the bone. The patient had a past medical history of mental disability and refractory Paget’s disease that was diagnosed 13 years prior in the setting of elevated alkaline phosphatase. At the time of diagnosis bone scan showed involvement of both tibias, pelvis and right femur stress fracture. She also had a right femoral fracture 7 years before the current presentation that was surgically fixed with an intramedullary rod. The patient had undergone 5 yearly infusions of Zoledronic acid with persistent elevated alkaline phosphatase.
During her clinic visit the patient endorsed left non-traumatic hip pain as well as difficulty walking over the last 2 weeks. Vital signs were within normal limits. On physical exam she appeared well developed, no acute distress was noted, normal heart rate, regular rhythm and normal heart sounds. Pulmonary effort was normal, no respiratory distress or abnormal sounds were appreciated. Musculoskeletal exhibited bilateral lower extremity bowing. No skin warmth, bony growths or tenderness on palpation were noted.
Lab work revealed ALP 277 u/l, bone specific alkaline phosphatase 95.9 (8.1 - 31.6), BUN 12 mg/dl, Creatinine 0.66 mg/dl, GFR 90, Calcium 9.0 mg/dl, Vitamin D 23.3 ng/mL.
She had been treating the hip pain with as needed NSAIDs. An X-ray of the left femur was ordered, and the study showed possible acute subcapital minimally displaced femoral neck fracture with minimal impaction in the setting of known Paget’s disease. The patient was then contacted and asked to present to the ER emergently for further evaluation and treatment.
Upon arrival to the Emergency Department, an MRI of the left hip was performed, demonstrating extensive Paget’s disease with no evidence of acute hip fracture.
Conclusions
It is essential to obtain an urgent x-ray in patients with Paget’s disease who presents with localized pain. However as this case demonstrates x-ray findings can be misleading due to underlying structural deformity of the bone and further imaging like CT or MRI may be necessary.
SAT-376 Secondary Hyperparathyroidism, an Untoward Complication of High Dose Phosphate Supplementation in Hereditary Hypophosphatemic Rickets
Authors: Pinjala Anusha , Gastelum Alheli Arce , Adel Maraqa Sima Abdel Rahman , Samec Joshua , Zena Mohsen 
Published: May 2020

Abstract
Background: Hereditary hypophosphatemic rickets is a debilitating disease with multiple skeletal abnormalities. Children exhibit rickets and growth failure, while adults exhibit bone pain, enthesopathy, HTN, and arthritis. Gene mutations involving renal phosphate reabsorption(PHEX, FGF23, SLC34A3) leads to renal phosphate wasting. Modes of inheritance include X-linked dominant (most common), autosomal dominant, and autosomal recessive. High dose oral phosphate supplements along with calcitriol are the mainstay of treatment. This can lead to complications of secondary hyperparathyroidism. Clinical Case: An 81-year-old Caucasian woman with PMH of X-linked dominant hypophosphatemic rickets (XLH), secondary osteoarthritis of both knees, HTN, and neuropathy was seen in the Endocrinology clinic. She was diagnosed with XLH 47 years ago and was taking calcitriol 0.5 mcg daily along with a phosphate supplement of 250 mg, 2 tablets 5 times a day. She underwent multiple corrective orthopedic procedures and bilateral knee replacements. On exam, she had short stature (height of 149.9 cm), arthritic changes of bilateral hand joints, and dentures. Starting in 2015, there was a rise in PTH to 101 pg/ml (normal 18.4-80 pg/ml). Over the next 4 years her PTH continued to rise to 182.6 pg/ml, 244.4 pg/ml, 350.6 in 2016, 2017, and 2019 respectively. A 24-hour urine collection revealed a calcium level of 175 mg (normal 100-250 mg/24 hours) and a phosphorus level of 2191 mg (normal 900-1300 mg/24 hours). In December of 2018, she developed hypercalcemia with a serum calcium level of 10.9 mg/dl(normal 8.5-10.5 mg/dl). We then tapered off calcitriol and decreased the phosphate supplements to TID. Despite these measures, her PTH continued to rise, but phosphorus remained normal. A Sestamibi scan showed hyperplasia of all four parathyroid glands, and a DXA scan showed normal bone mineral density. Serum alkaline phosphatase was normal. We decreased her phosphate supplements to BID and started cinacalcet at 30 mg BID. Conclusion: This case illustrates the challenges of primary and secondary hyperparathyroidism when treating XLH. It is proposed that an increased oral phosphate load transiently lowers ionized calcium in serum, which then stimulates PTH secretion. Increased mineralization of bone is another possible explanation of this phenomenon. Persistent parathyroid stimulation can cause hyperplasia of parathyroid glands, nephrocalcinosis, hypertension, and renal failure. Early identification, temporary discontinuation of oral phosphate, and an increase of calcitriol will lower PTH. The FDA approved burosumab for the treatment of XLH in 2018. Future studies are needed to see if burosumab therapy prevents the above complications associated with traditional treatment.
MON-602 The Efficacy and Safety of Sodium-Glucose Transport Protein 2 (SGLT-2) Inhibitors for Weight Loss Among Individuals Without Diabetes: A Systematic Review and Meta-Analysis
Authors: Cabrera Carmen Carina , Francisco Miguel Enrico , Dampil Oliver Allan Castillo 
Published: May 2020

Abstract
Background
With the growing prevalence of obesity and its associated metabolic consequences, new strategies for safe and effective weight loss are called for. SGLT2i is a class oral antidiabetic agents that lowers glucose levels through renal glucose loss, with weight reduction as a consequence. Hence, its role in diabetes and obesity is well-recognized. However, its use among individuals without diabetes for safe and durable weight loss has not yet been sufficiently evaluated, although initial studies are promising.
Objective
To determine the efficacy and safety of SGLT2i compared to placebo among subjects without diabetes mellitus in terms of weight loss and adverse effects.
Methods
A meta-analysis was conducted on randomized controlled trials (RCTs) comparing different SGLT2i and placebo among patients without diabetes mellitus using RevMan 5.3 software.
Results
Five trials involving 779 patients met the eligibility criteria. SGLT2i used in these studies include Canagliflozin, Dapagliflozin, Sergliflozin and Remogliflozin with treatment duration ranging from 2 to 26 weeks.
Pooled data of these 5 trials showed a significant difference in weight loss among subjects given SGLT2i (MD -1.34 kg [95% CI -1.51, -1.17]; p &lt; 0.00001, I2 = 0%) as compared to placebo. Four studies reported change in BMI as an outcome measure, likewise showing a significant difference favoring the use of SGLT2i (MD -0.50 [95% CI -0.56, -0.44]; p &lt; 0.0001, I2 = 0%). Two RCTs reported the percentage of weight loss. There was a significantly higher proportion of subjects achieving &gt;5% weight loss among those given SGLT2i (RR 1.61 [95% CI 1.09, 2.38]; p = 0.02, I2 = 0%). There was no significant difference in the proportion of subjects who achieved &gt;10% weight loss (RR 1.42 [95% CI 0.60, 3.33]; p = 0.42, I2 = 12%). Urogenital infections were more common in the SGLT2i group (RR 2.62 [95% CI 1.76, 3.91], p &lt; 0.00001, I2 = 0%) as reported in 4 studies. Only one study reported occurrence of hypoglycemia which did not differ significantly between both groups.
Conclusion
Although this meta-analysis shows a statistically significant decrease in weight (-1.34 kg, [95% CI -1.51, -1.17]) with the use of SGLT2i among subjects without diabetes, this might not be clinically relevant. With the increased risk of urogenital infections with its use, there is insufficient evidence to recommend its routine use as monotherapy for weight loss outside the population of individuals with diabetes.
References
Pereira MJ, Eriksson JW. Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs (2019) 79:219-230.
MON-647 Mechanisms of Insulin Resistance in Skeletal Muscle in Women with PCOS
Authors: Moreno-Asso Alba , McIlvenna Luke C , Patten Rhiannon K , McAinch Andrew J , Rodgers Raymond J , Stepto Nigel K 
Published: May 2020

Abstract
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder affecting metabolic, reproductive and mental health of 8-13% of reproductive-age women. Insulin resistance (IR) appears to underpin the pathophysiology of PCOS and is present in approximately 85% of women with PCOS. This underlying IR has been identified as unique from, but synergistic with, obesity-induced IR (1). Skeletal muscle accounts for up to 85% of whole body insulin-stimulated glucose uptake, however, in PCOS this is reduced about 27% when assessed by hyperinsulinemic euglycemic clamp (2). Interestingly, this reduced insulin-stimulated glucose uptake observed in skeletal muscle tissue is not retained in cultured myotubes (3), suggesting that environmental factors may play a role in this PCOS-specific IR. Yet, the molecular mechanisms regulating IR remain unclear (4). Previous work suggested that Transforming Growth Factor Beta (TGFβ) superfamily ligands may be involved in the metabolic morbidity associated with PCOS (5). In this study, we investigated the effects of TGFβ1 (1, 5ng/ml), and the Anti-Müllerian hormone (AMH; 5, 10, 30ng/ml), a novel TGFβ superfamily ligand elevated in women with PCOS, as causal factors of IR in cultured myotubes from women with PCOS (n=10) and healthy controls (n=10). AMH negatively affected glucose uptake and insulin signalling increasing p-IRS1 (ser312) in a dose-dependent manner in myotubes from both women with and without PCOS. AMH did not appear to activate the canonical TGFβ/BMP signalling pathway. Conversely, TGFβ1 had an opposite effect in both PCOS and control myotubes cultures, decreasing phosphorylation of IRS1 (ser312) and enhancing glucose uptake via Smad2/3 signalling. In conclusion, these results suggest that AMH may play a role in skeletal muscle IR observed in PCOS, however, further research is required to elucidate its mechanisms of action and broader impact in this syndrome. References: (1) Stepto et al. Hum Reprod 2013 Mar;28(3):777-784. (2) Cassar et al. Hum Reprod 2016 Nov;31(11):2619-2631. (3) Corbould et al., Am J Physiol-Endoc 2005 May;88(5):E1047-54. (4) Stepto et al. J Clin Endocrinol Metab, 2019 Nov 1;104(11):5372-5381. (5) Raja-Khan et al. Reprod Sci 2014 Jan;21(1):20-31.
OR01-06 Resistance to Thyroid Hormone Beta Is Associated with an Increase in Hepatic Fat Measured by Transient Elastography (Fibroscan®) with Controlled Attenuation Parameter (CAP)
Authors: Chaves Carolina Marques , Bruinstroop Eveline , Refetoff Samuel , Yen Paul Michael , Anselmo Joao 
Published: May 2020

Abstract
Hepatic regulation of lipid metabolism is dependent on thyroid hormone receptors (TRs) with TRβ as the predominantly expressed TR isoform in the liver. Patients with resistance to thyroid hormone (RTH) harboring mutations in the THRB gene have loss-of-function of TRβ. Thus, we investigated whether these patients can present with alterations in the lipid homeostasis.
We evaluated hepatic fat content and metabolic parameters in patients bearing the R243Q mutation of THRB gene (n=21) and in their non-affected (WT) first degree relatives (n=22). All participants belonged to the same family, lived in the same small island, therefore exposed to similar environmental conditions. Family members with disorders known to affect lipid metabolism as well as a history of drinking habits of more 30 g alcohol/day were excluded. Whenever possible, medications were suspended one month before the tests. Hepatic fat content was estimated by transient elastography (FibroScan®, TE) with controlled attenuation parameter (CAP) as a noninvasive marker of hepatic steatosis. Measurements of CAP and metabolic parameters were carried after an overnight fast. The observers were blinded to the status of the patients.
There were no significant difference between the two groups, RTHβ and WT respectively, in age (mean±SD) 36±11 years (range 18-55) and 34±9 years (19-59) and body mass index, BMI, 21.9 Kg/m2 (14.2-31.7) and 23.8 Kg/m2 (18.9-37.7). CAP values were significantly higher in RTHβ patients when compared to those measured in their WT relatives, 263±21 dB/m and 218.7±43 dB/m, respectively (P&lt;0.001). Measurements of CAP correlated positively with age and BMI in the WT group (r=0.56; P&lt;0.05 and r=0.59; P&lt;0.05 respectively) but not in the group of RTHβ (r=0.19; P&gt;0.05 and r=0.21;P&gt;0.05. The lipid profile was not significant difference between the two group regarding total cholesterol (165±27 and 175±30 mg/dl), LDL cholesterol (103±16 and 113±29 mg/dl) and tryglicerides (115±45 and 108±43mg/dl). However, the HDL cholesterol was significantly lower in RTHβ patients (40±8 and 52±10 mg/dl; P&lt;0.006). Glycemia, insulin levels and HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) were within the normal range and showed no significant differences between the two groups.
In conclusion, RTHβ was associated with hepatic steatosis indicating that the TRβ dependent signaling of thyroid hormone plays an important role in lipid homeostasis. This finding further emphasizes the rational for the development of thyroid hormone analogues selective for TRβ which may offer alternatives for treatment of lipid-associated hepatic disorders without generating cardiac toxicity or accelerated bone loss.
SAT-715 Bisphenol-A Alters Pancreatic B-Cell Proliferation and Mass in an Estrogen Receptor Beta-Dependent Manner
Authors: Nadal Angel , Boronat-Belda Talia , Quesada Ivan , Fuentes Esther , Gustafsson Jan-Ake , Alonso-Magdalena Paloma 
Published: May 2020

Abstract
Bisphenol-A (BPA) is one of the highest volume chemicals produced worldwide. It is used as the base compound in the manufacture of polycarbonate plastics, epoxies and resins. Humans are consistently exposed to BPA and consistently it has been detected in the majority of individuals examined. Experimental research in animals, as well as human epidemiological studies, converge to conclude that BPA is a risk factor for the development of type 2 diabetes. In previous studies we have demonstrated that the exposure to BPA during embryonic development promote an increment of pancreatic β-cell mass. This was correlated with increased β-cell division and altered global gene expression in pancreatic β-cells. The aim of this work was to determinate whether ERβ was involved in the in the β-cell mass and proliferation increment observed in male mice offspring. ERβ+/- pregnant mice were treated with vehicle or BPA (10 μg/kg/day) from day 9 to 16 of gestation. Offspring pancreatic β-cell mass was measured at postnatal day 0 (P0) and 30 (P30). For ex vivo experiments Wild-type (WT) and ERβ-/- neonates as well as adult male and female mice were used. For in vitro, single islets cells were cultured for 48 h in the presence of 10 μmol/L BrdU, and vehicle, BPA (1, 10, 100 nM) or the specific ERβ agonist WAY200070 (1, 10, 100 nM). β-cell proliferation rate was quantified as the percentage of BrdU-positive pancreatic β-cells. In vivo exposure to BPA during pregnancy promoted an increment of pancreatic β-cell mass and proliferation in WT mice at P30 which was absent in ERβ -/- mice. In order to explore if these changes were related to a direct action of BPA on pancreatic β-cell division we performed a series of ex vivo experiments. Augmented β-cell proliferation rate was observed in BPA-exposed β-cells isolated from both adult male and female WT animals in comparison to controls. The increment was significant at all BPA doses tested. The effect was imitated by the selective ERβ agonist, WAY200070, and was abolished in cells from ERβ-/- mice. We also explored the effects of BPA in pancreatic β-cells from neonates and found an increment in BPA-exposed cells compared to controls, although the difference was only significant at the dose of 1 nM. A similar effect was observed in neonate cells treated with WAY200070 (10 nM). The effects on β-cell replication were abolished in cells from ERβ-/- neonate mice treated either with BPA or WAY200070. Our findings suggest that BPA modulate pancreatic β-cell growth and mass in an ERβ-dependent manner. This could have important implications for metabolic programming of T2DM. Ministerio de Economía y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) grants BPU2017-86579-R (AN) and BFU2016-77125-R (IQ); Generalitat Valenciana PROMETEO II/2015/016 (AN). CIBERDEM is an initiative of the Instituto de Salud Carlos III.
SUN-740 Low-Dose Dihydrotestosterone Lowers Lipogenic Master Regulator in Liver and Adipose Tissue from Female Mice
Authors: Seidu Tina , Andrisse Stanley 
Published: May 2020

Abstract
Hyperandrogenemia (HA) and insulin resistance (IR) are hallmarks of polycystic ovary syndrome (PCOS), a common endocrine disorder that affects 1 in 10 women. These hallmarks are also integral elements of non-alcoholic liver disease (NALFD), a disorder that is common in women with PCOS. Administering low dose dihydrotestosterone (DHT) induced a lean female mouse model with a PCOS-like phenotype, displaying IR and NAFLD. The molecular mechanism of HA-induced NAFLD has not been determined. We hypothesized that low dose DHT would interrupt hepatic lipid metabolism leading to NAFLD. To investigate the role of androgens on the master regulator of lipogenesis, sterol regulatory element-binding protein 1 (SREBP1), we extracted white adipose tissue (WAT), liver, and skeletal muscle from wild-type, control and low dose DHT female mice; and performed Western blot and real-time quantitative PCR (qRT-PCR) analysis of lipogenic intermediates of the tissue homogenates. Low-dose DHT lowered the active form of cytosolic SREBP1 in the liver and WAT compared to controls. Additionally, low dose DHT lowered inactive SREBP1 in the liver. However, the condition did not alter the levels of the active and inactive forms of SREBP2 in the liver and WAT, though the active form was lowered in skeletal muscle. Further, p-ACC levels were unaltered in liver and WAT. FAS levels were unchanged in WAT and skeletal muscle. Taken together, our findings support the hypothesis that cytosolic SREBP1 decreased due to its translocation to the nucleus, where it regulates lipogenic protein levels. We speculate that low-dose DHT promotes the translocation of SREBP1 from the cytosol to the nucleus to influence lipogenic gene expression leading to increased lipogenesis contributing to NAFLD.
MON-624 Effect of Whole Body Vibration on Glycemic Control in Adults with Type 2 Diabetes
Authors: Michels Manuela de Lucca , d’Acampora Ana Clara , Spivakoski Camila Sartor , Mattje Priscila Nobre Dantas , Réus Bruna da Silva , Alves Débora Monteiro dos Santos , Pilletti Karine , Ronsoni Marcelo Fernando , Hohl Alexandre , van de Sande-Lee Simone 
Published: May 2020

Abstract
Introduction: Physical activity plays an important role in glycemic control in patients with type 2 diabetes, but overall adherence rate is low. For patients not able or willing to engage in regular physical exercise, whole body vibration comes as a potential alternative. Objective: To evaluate the effect of 28Hz whole body mechanical vibration on glycemic control and other metabolic parameters in patients with type 2 diabetes. Methods: 24 adults with type 2 diabetes on oral antidiabetic agents, with a baseline HbA1c between 6.5 and 9.0%, were randomized into two groups. The control group (CG) was advised to adopt lifestyle modifications, and the intervention group (IG) received the same orientations and used a 28 Hz whole body vibrating platform daily for 20-30 minutes during 12 weeks. Results: Data from 22 patients were analyzed (one from each group was excluded). Baseline characteristics of both groups were similar except for triglycerides, which were higher in the CG (111.8±39.9 mg/dL vs. 188.9±68.8 mg/dL, p&lt;0.05). After 12 weeks, there was a significant reduction in glycated hemoglobin in the IG (7.69±0.49 vs. 7.17±0.77%, p&lt;0.05), not observed in the CG (8.05±0.98 vs. 7.92±1.07%, p=0.52). A non-significant trend for weight loss in IG was observed (78.14±10.47 vs. 77.14±11.08Kg, p=0.069). There were no significant differences between the groups regarding fasting blood glucose or any other clinical and biochemical variables analyzed. Conclusion: This study suggests an improvement in glycated hemoglobin at 12 weeks with the use of the 28Hz vibration platform in patients with type 2 diabetes. However, further studies with a larger number of patients and longer follow-up are needed to better define the role of whole body vibration as an adjuvant in glycemic control.