bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-356 Burosumab Resulted in Greater Clinical Improvements Compared with Higher-dose Conventional Therapy in Children with X-linked Hypophosphatemia (XLH)
Authors: Imel Erik A , Chen Angel , Chang Ting , Roberts Mary Scott , Ward Leanne Marie 
Published: May 2020

Abstract
In XLH, excess circulating FGF23 causes hypophosphatemia, rickets, lower limb deformity, and impaired growth and mobility. An active-controlled, phase 3 trial (CL301; NCT02915705) showed treatment with burosumab, a fully human monoclonal antibody against FGF23, resulted in significantly greater improvements in all of these outcomes in children with XLH, compared with continuing oral phosphate and active vitamin D as conventional therapy (Pi/D) per established guidelines. In a post-hoc analysis, we compared children who received burosumab vs those who received an average 64-week oral phosphate daily dose &gt;40 mg/kg (higher-dose Pi) vs ≤40 mg/kg (lower-dose Pi). Sixty-one children with XLH (1–12 years-old) were randomized 1:1 after a 7-day Pi/D washout to receive burosumab (n=29) starting at 0.8 mg/kg subcutaneously Q2W or to resume Pi/D (n=32) titrated by their investigator, for 64 weeks. Eligibility criteria included Rickets Severity Score (RSS) ≥2.0 despite prior Pi/D treatment. Of the 32 subjects randomized to Pi/D, 12 received average higher-dose Pi and 20 received average lower-dose Pi (as specified above). The primary endpoint was rickets healing, using the Radiographic Global Impression of Change (RGI-C) Scale. At week 64, the improvement in the least square (LS) mean (LS mean [±SE; 95%CI]) RGI-C Global Score for rickets was greater on burosumab (+2.06 [0.072; 1.92, 2.20]) compared with either higher-dose (+1.02 [0.241; 0.55, 1.50]) or lower-dose (+1.04 [0.162; 0.73, 1.36]) Pi. The mean decrease in the total RSS from baseline was also greater on burosumab (-2.23 [0.117; -2.46, -2.00]) compared with higher-dose (-0.87 [0.264; -1.39, -0.35] or lower-dose (-1.09 [0.180; -1.45, -0.74]) Pi. Similarly, the mean RGI-C Lower Limb Deformity Score was greater on burosumab (+1.25 [0.170; 0.92, 1.59]) compared with either higher-dose (+0.32 [0.188; -0.05, 0.69]) or lower-dose (+0.26 [0.146; -0.02, 0.55]) Pi. Adverse events including hypersensitivity and injection site reactions, were more frequent with burosumab, and were mild to moderate in severity overall. No discontinuations occurred. In conclusion, children with XLH treated with burosumab had greater improvements in rickets and lower limb deformity compared with subjects receiving higher or lower doses of Pi.
SUN-675 Breast Cancer Treatment Causes Diabetes
Authors: Silparshetty Santh V S , Bhatt Bankim 
Published: May 2020

Abstract
Introduction: Alpelisib (BYL719) a PI3K p110alpha inhibitor, was recently FDA approved to treat postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA gene mutation positive, advanced or metastatic breast cancer following progression on endocrine-based regimen. A major side effect of this cancer therapy is severe hyperglycemia. Case Report: 78 year old female with prediabetes, presents with 5 days of polyuria, polydipsia, blurred vision, severe fatigue and pre-syncope. Random blood glucose at home was &gt;500mg/dL. She has a history of ER, PR positive and HER2 negative invasive adenocarcinoma of right breast with bone metastases that has progressed on chemotherapy, radiation therapy and hormone therapy. Her PI3KCA gene mutation was positive and she was started on alpelisib a week prior to hospitalization. Physical examination revealed heart rate 98/min, blood pressure 160/74mmHg, BMI 21, dry oral mucosa and reduced skin turgor. Urinalysis showed &gt;1000mg/dL glycosuria. Random plasma glucose was 354mg/dL. Creatinine was 1.07mg/dL (baseline 0.70mg/dL). She was resuscitated with IV saline and started on glimepiride 2mg oral twice daily, glargine 5 units at bedtime with correctional insulin regimen. Despite therapy, plasma glucose remained 180-350mg/dL. Discontinuation of alpelisib, rapidly improved her plasma glucose. Discussion: PI3K (phosphatidylinositol 3 kinase) activation by insulin is a key step in whole body glucose metabolism. PI3K inhibition leads to glycogen breakdown in liver and marked insulin resistance by reduced glucose uptake in skeletal muscle and adipose tissue. Treatment options using oral agents or insulin are limited in these patients. As more patients with cancer are approved for treatment with PI3K inhibitors, clinicians need to be more aware of the mechanism of hyperglycemia to effectively manage it. More evidence based consensus is needed on management of hyperglycemia with PI3K inhibition.
SAT-398 The Use of Imaging in Primary Hyperparathyroidism
Authors: Broome David Tyler , Naples Robert , Bailey Richard , Bena James F , Scharpf Joseph , Skugor Mario 
Published: May 2020

Abstract
Primary hyperparathyroidism is characterized by excessive dysregulated production of parathyroid hormone (PTH) by 1 or more abnormal parathyroid glands. Preoperative localization is important for surgical planning in primary hyperparathyroidism. Previously, it had been published that ultrasound (sensitivity of 76.1%, positive predictive value of 93.2%) and nuclear scintigraphy (Sestamibi-SPECT) (sensitivity of 78.9%, and a positive predictive value of 90.7%) are first line imaging modalities1. Currently, the imaging modality of choice varies according to region and institutional protocol. The aim of this study was to evaluate the imaging modality that is associated with an improved remission rate based on concordance with operative findings. A secondary aim was to determine the effect of additive imaging on remission rates. This was an IRB-approved retrospective review of 2657 patients with primary hyperparathyroidism undergoing surgery at a tertiary referral center from 2004–2017. Analyses were performed with SAS software using a 95% confidence interval (p&lt;0.05) for statistical significance. After excluding re-operative and familial cases, 2079 patients met study criteria. There were 422 (20.3%) male and 1657 (79.7%) female patients with a mean age of 66 (+12.2) years, of which 1723 (82.9%) of patients were white and 294 (14.1%) patients were black. Ultrasound (US) was performed in 1891 (91.9%), sestamibi with SPECT (sestamibi/SPECT) in 1945 (93.6%), and CT in 98 (4.7%) patients. Of these, 1721 (82.8%) had combined US and sestamibi/SPECT. US was surgeon-performed in 94.2% of cases and 89.9% of the patients underwent a four gland exploration. Overall, US concordance was 52.4%, sestamibi/SPECT was 45.5%, and CT was 45.9%.US and sestamibi/SPECT both had an improved remission rate if concordant with operative findings, while CT had no effect (US p=0.04; sestamibi/SPECT p=0.01; CT p=0.50). The overall remission rate was 94% (CI=0.93–0.95), however, increasing the number of imaging modalities performed did not increase the remission rate (p=0.76) or concordance with operative findings (p=0.05). Despite having low concordance rates, US and sestamibi/SPECT that agreed with operative findings were associated with higher remission rates. Therefore, when imaging is to be used for localization, our data support the use of US and sestamibi/SPECT as the initial imaging modalities of choice for preoperative localization.
1Kuzminski SJ, Sosa JA, Hoang JK. Update in Parathyroid Imaging. Magn Reson Imaging Clin N Am. 2018;26(1): 151–166.
SAT-016 Analytical Performance and Clinical Value of AMH Testing
Authors: Sluss Patrick M , Palomaki Glenn , Kumar Ajay , Morrison Anthony , Kalra Bhanu , ALPADI KANNAN 
Published: May 2020

Abstract
The clinical uses for of anti-Mullerian hormone (AMH) measurements have risen dramatically over the past 5 years. This increase has been driven by the release of fully automated immunoassay systems with European and FDA approval of AMH measurements for assessing ovarian reserve in women presenting at fertility clinics. Most recently the MenoCheck® AMH method was cleared by FDA as an aid in determining menopausal status in women over the age of 40. Arguably much, of the increased use of AMH measurements is due more to greater test availability for infertility than to strong data supporting its clinical utility. Furthermore, few clinicians realize that the current methods for measuring AMH utilize antibodies with difference specificities, non-commutable calibrator materials, and significantly difference analytical performance characteristics.
This presentation will summarize the analytical validation of MenoCheck® AMH methodology and results of the assessment of clinical value. This method is calibrated with recombinant human AMH in a non-covalent complex associated with the cleaved N-terminal portion of the AMH prohormone protein (the major circulating form of AMH) and demonstrates commutability with native human AMH. Validation studies conformed with published Clinical Laboratory Standards Institute guidelines. Values generated by the method were not commutable to other widely available methods based on method comparison studies using control materials or unadulterated serum from normally cycling women. Clinical value assessment was possible only because of a limit of quantitation enabling measurement of AMH in the majority of perimenopausal women. SWAN study specimens carefully annotated with relevant clinical information, including date of their final menstrual period, were available from women sampled and examined during their menopausal transition. The impact of method-specific differences among the various assay systems and their implications for intended clinical use of AMH testing will be discussed. Clinicians and translational investigators must consider these technical specifications when ordering and interpreting results from AMH testing.
SAT-LB137 Rescue of Misfolded G-Protein Coupled Estrogen Receptor, GPER, from the Endoplasmic Reticulum via Natural and Synthetic Estrogens
Authors: Rouhimoghadam Milad , Dong Jing , Thomas Peter , Filardo Edward Joseph 
Published: May 2020

Abstract
GPER bears structural and functional characteristics shared by members of the G-protein coupled receptor (GPCR) superfamily, the largest class of cell surface receptors, with more than 800 members encoded in the human genome. GPER is localized predominately in intracellular membranes, in many but not all cell types, and its surface expression is modulated by steroid hormones and during tissue homeostasis. An intracellular staining pattern is not unique among GPCRs, which deploy a diverse array of posttranslational regulatory mechanisms to determine cell surface expression, effectively regulating cognate ligand binding and activity.
Here, we show nascent GPER undergoes strict quality control via endoplasmic reticulum associated degradation (ERAD) requiring direct poly-ubiquitinylation of GPER and valosin-containing protein VCP/p97-mediated segregation of misfolded proteins from the ER membrane to the cytoplasm for delivery to the 26S proteasome. Specifically, we find that inhibition of p97 using the pharmacological compound, CB-5083, or by doxycycline-inducible p97 shRNA results in the accumulation of immature glycosylated GPER in the ER. Inhibition of proteasome function facilitates anterograde trafficking with the transport of nonfunctional GPER to the plasma membrane as indicated by no increase in specific estrogen binding using 3H-17β-estradiol in a radioreceptor assay. The forward trafficking of misfolded GPER requires transit through the Golgi as treatment with brefeldin A (BFA) prevents GPER plasma membrane expression. Substitution of all three lysines (K333, K342, and K357) encoded in the cytoplasmic tail of GPER with arginines blunts its polyubiquitinylation and allows GPER to evade degradation by quality control but does not result in increased plasma membrane expression suggesting that additional structural motifs encoded within GPER control its anterograde trafficking. In contrast, functional GPER is recovered at the plasma membrane of human SKBR3 breast cancer cells treated with either 17β-estradiol or the GPER selective antagonist, G15, in the presence of cycloheximide resulting in increased surface GPER. Thus, our findings suggest that estrogens, both natural and synthetic, can function as pharmacochaperones capable of promoting the correct folding of GPER and enhanced expression of functional GPER at the plasma membrane.
SAT-LB104 Maternal Non-Nutritive Sweeteners Consumption Perturbs Development of Melanocortin Circuits Causing Long-Term Metabolic Alterations in the Offspring
Authors: Park Soyoung , Jang Alice , Lowy Josephine , Bouret Sebastien G 
Published: May 2020

Abstract
Maternal Non-Nutritive Sweeteners Consumption Perturbs Development of Melanocortin Circuits Causing Long-Term Metabolic Alterations in the Offspring Soyoung Park1, Alice Jang1, Josephine Lowy1, Sebastien G Bouret2 1Developmental Neuroscience & Diabetes and Obesity Programs, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, USA. 2 Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, UMR-S 1172, Lille, 59000, France.
With the growing prevalence of obesity and diabetes, including among pregnant women, non-nutritive sweeteners (NNS) have been widely used as an alternative to sugar in the attempt to deliver a sweet taste without excessive caloric load. However, there is little evidence regarding their biological effects particularly during critical periods of growth and development. In this study, we aimed to investigate whether maternal NNS consumption causes long-term neurodevelopmental and metabolic perturbations in the offspring. Adult female wild-type mice were exposed to either water (control), aspartame (0.03%), or rebaudioside A (0.02%) throughout pregnancy and lactation. Adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal NNS consumption impaired pro-opiomelanocortin axonal projections to the paraventricular nucleus of the hypothalamus as well as reduced parasympathetic innervation of pancreatic islets. Taken together, our data indicate that maternal NNS consumption causes neurodevelopmental abnormalities in the offspring that may contribute to lifelong metabolic dysregulations.
MON-371 The Case of Dueling Femurs
Authors: Patel Richa , Berlioz Ana Ramirez , Chinnakotla Bhavana , Kurukulasuriya Lilamani Romayne Goonetilleke 
Published: May 2020

Abstract
Introduction: Paget’s disease of the bone is characterized by excessive osteoclastic bone resorption followed by formation of disorganized bone; which is often focal. Bone pain and deformities are common features and it often leads to complications such as pathological fractures, deafness or neurologic deficits. Elevated bone turnover markers and alkaline phosphatase reflect ongoing exaggerated bone resorption and osteoblastic activity. We present an unusual scenario of post-menopausal osteoporosis and Paget’s disease occurring in the same patient.
Clinical Case: 86-year-old female with history of Type 2 Diabetes Mellitus, Hypertension,
Hypothyroidism, degenerative joint disease of lumbar spine with prior interbody fusion and laminectomy was referred to our clinic by Orthopedics for evaluation of newly diagnosed Paget’s disease. 2 months ago, she noticed severe right hip pain limiting daily activities. She denied any history of falls, fractures or family history of Paget’s. Physical exam was notable for tenderness to right sacro-iliac joint and right femoral trochanteric region. Work up included MRI of Lumbar spine and Pelvis, Pelvis X-ray, DEXA scan and routine blood work.
Interestingly, her DEXA scan showed T score of +2.9 in Right hip and -3.1 in Left hip. On Pelvis X-ray cortical thickening, coarse trabecula and osteoarthritic changes were noted in right femur and hip, consistent with Paget’s disease. Left femur showed strikingly thinner cortices compared to the right, due to underlying osteoporosis. MRI of lumbar spine and pelvis was consistent with polyostotic Paget’s involving L3-L5, Sacrum and Right femur. Nuclear bone scan showed areas of uptake including anterior calvarium, lumbar spine, right hip, right femur, 8th rib, left mid tibia and 1st metatarsal of left foot. Since the distribution of uptake seemed atypical for Paget’s, a skeletal survey was obtained which was negative for bone lesions suggestive of malignancy.
Laboratory testing revealed serum calcium 9.8mg/dL(8.4–10.2), 25-Hydroxy Vitamin D 30ng/dL(20–30), PTH 45.6pg/mL (15–65), Alkaline Phosphatase 370U/L (35–104), Procollagen I intact N-terminal 516mcg/L (16–96) and N-Terminal Telopeptide (NTX) 126.4 nM BCE (6.2–19).
Patient received one dose of IV Zoledronic acid with modest improvement in hip and lower back pain. She continues to take Calcium carbonate 600mg twice daily and vitamin D3 1000IU once daily. We plan to see her in follow up in 3 months with repeat levels bone turnover markers.
Conclusion: This is a unique case of Paget’s disease and osteoporosis, two very different diseases of metabolic bone disorder spectrum found in one patient. Treatment of Paget’s disease is indicated for pain reduction, prevention of fractures and deformities and to prevent disease progression in weight bearing areas. Bisphosphonates can target pathology of both diseases by reducing osteoclastic bone resorption.
SAT-LB60 Discordant Biological Parameters of Remission in Acromegaly Do Not Increase the Risk of Hypertension or Diabetes: A Study With the Liege Acromegaly Survey Database
Authors: Amodru Vincent , Petrossians Patrick , Colao Annamaria , Delemer Brigitte , Maione Luigi , Neggers Sebastian J C M M , Decoudier Benedicte , Kamenicky Peter , Castinetti Frederic , Hana Vaclav , Pivonello Rosario , Carvahlo Davide , Brue Thierry Christian , Beckers Albert M , Chanson Philippe , CUNY Thomas 
Published: May 2020

Abstract
Introduction: Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease, however a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of acromegalic comorbidities in patients with congruent GH and/or IGF-1 levels vs discordant biochemical parameters. Methods: Retrospective analysis of the data of 3173 patients from the Liège Acromegaly Survey (LAS) allowed to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning diabetes mellitus (DM) and hypertension (HT) both at diagnosis and at last follow-up. We recorded for all the patients the number of antihypertensive and antidiabetic drugs used at the first evaluation and at last follow-up. Results: Ninety-nine patients belonged to the REM group (Concordant parameters), sixty-five patients were considered as GHdis and 26 patients were considered as IGF-1dis. At diagnosis, 63 patients (33.1%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of number of anti-HT and anti-diabetic drugs at diagnosis versus last follow-up (mean duration=7.3+/-4.5years) between all 3 groups. Discussion: The results highlight that the long-term outcome of acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.
SUN-LB133 Analysis of Clinical Characteristics and Gene Mutation in Four Cases of Gitelman Syndrome
Authors: Yao Bin 
Published: May 2020

Abstract
Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by renal salt wasting with secondary hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria. GS was found to be caused by mutations in SLC12A3 encoding the thiazide-sensitive sodium chloride cotransporter (NCCT) on the apical membrane of distal convoluted tubule. The prevalence worldwide is estimated at approximately 1:40,000, making it one of the most frequent inherited renal tubular disorders. To date, over 400 mutations scattered throughout SLC12A3 have been identified in GS patients. The majority of patients are compound heterozygous for SLC12A3 mutations, but a significant number of GS patients are found to carry only a single SLC12A3 mutation. The type of the SLC12A3 mutation may be a determinant factor in the severity of GS. The purpose of this study is to analyze clinical characteristics and gene mutation in four cases of GS.
Methods: Four patients with closely resembling Gitelman syndrome was selected.
Results: Six SLCl2A3 gene mutations were found in these four patients. There were one SLCl2A3 homozygous mutation in case 1 and case 3, and two SLCl2A3 heterozygous mutations in case 2 and case 4, respectively. This six gene mutations include missense mutations, frameshift mutations, and nonsense mutations. Four patients were diagnosed with Gitelman syndrome. Case 4 is the most severe with severe hypokalemia, accompanied by ventricular arrhythmias, which may be related to the presence of two SLC12A3 gene mutations in the patient.
Conclusions: Four patients in this study were diagnosed with Gitelman syndrome based on their clinical characteristics and genetic testing results. For patients with hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria need to exclude Gitelman syndrome.
Key words: Gitelmen Syndrome, Mutations, SlC12A3 gene
SAT-LB65 A Rare Existence
Authors: Bedia Jiselle Aimee Yaplito , Gomez Maria Honolina S 
Published: May 2020

Abstract
Primary hyperparathyroidism is a common endocrine disorder of metabolism usually due to a parathyroid adenoma. Although, the clinical presentation of primary hyperparathyroidism has changed from Albright’s description of a disease of bones and stones, the central target organs affected by this disorder continue to be the skeleton and kidneys. With the advent of routine biochemical screening, the typical diagnosis of primary hyperparathyroidism is no longer accompanied by overt skeletal and renal involvement. Majority of the cases of primary hyperparathyroidism are due to parathyroid adenomas. Giant glands were defined as greater than the 95th percentile, characterized as glands weighing &gt; 3.5 grams.
This present case in a 54-year old female is a rare case of primary hyperparathyroidism secondary to a giant parathyroid adenoma measuring 10.7 x 8.0 x 40.0 cm and weighing 145 grams, the largest giant parathyroid adenoma reported to date, with co-existent silent thymoma, multinodular goiter and osteosclerosis of the vertebral spine, metaphorically known as the “rugger-jersey spine”. The association between thymoma and parathyroid adenoma is rare, and only 3 cases have been reported in the literature. We characterized the correlation of preoperative imaging, intraoperative location, and postoperative course, including significant postoperative hypoparathyroidism, as compared to other patients with PHPT to determine whether giant adenomas represent a clinical entity with distinct clinical characteristics.
Keywords: primary hyperparathyroidism, giant parathyroid adenoma, rugger-jersey spine, thymoma
Abbreviation
PHPT
Primary hyperparathyroidism