bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-711 Association of Single Nucleotide Polymorphisms of CYP11B2, CYP11B1 and CYP17A1 with Primary Aldosteronism in a Multi-Ethnic Malaysian Cohort
Authors: Azam Afifah , Shahar Mohammad Arif , Gany Siti Liyana Saud , Sukor Norlela , Kamaruddin Nor Azmi , MacKenzie Scott Mackay , Azizan Elena Aisha 
Published: May 2020

Abstract
Primary aldosteronism (PA), also known as Conn’s syndrome, is a common curable cause of hypertension. Family studies of essential hypertensive patients suggest that heritable genetic factors play a role in blood pressure regulation1. Interestingly, single nucleotide polymorphisms (SNP) in genes encoding enzymes involved with adrenal steroidogenesis, CYP11B2, CYP11B1 and CYP17A1, associate with increased risk of hypertension2. Therefore, we analysed whether selected SNPs in these genes are associated with PA. We performed an association study using genotype imputation for selected SNPs of the steroidogenic enzyme genes CYP11B2 (rs4546, rs1799998, rs13268025), CYP11B1 (rs6410, rs149845727), and CYP17A1 (rs1004467, rs138009835, rs2150927) from a pilot genome wide association study of Malaysian PA patients and healthy controls which was merged with the Singapore Genome Variation Project (SGVP) population dataset3. Genotype imputation for minor and major alleles was validated using PCR sequencing (n&gt;10 for each genotype). Further, one SNP from each steroidogenic enzyme (CYP11B2:rs1799998, CYP11B1:rs6410 and CYP17A1:rs1004467) was validated using commercial TaqMan genotyping assays on the ABI 7000 Sequence Detection System which was performed on 149 PA patients and 78 non-hypertensive healthy individuals. Case-control genetic association analysis was performed at http://www.oege.org/software/orcalc.html and the association between genotypes and phenotypes was done using the independent-samples Kruskal-Wallis test on SPSS (version 25). The Minor Allele Frequencies (MAFs) for rs1004467, rs6410 and rs1799998 were similar to East Asian populations but differed significantly different from European, African, American and South Asian populations (rs1004467 MAF: C=0.258/298, rs6410 MAF: A=0.265/298, rs1799998 MAF: C=0.225/298). In Chinese patients matched by gender, heterozygotes for rs6410 had significantly increased risk of PA compared to common homozygotes (OR: 3.15, 95% CI: 1.01–9.8, p=0.04). Across patients of different ethnicity, the distribution of aldosterone levels was significantly different (p=0.039). In summary, only SNP rs6410 in Chinese patients matched by gender showed association with PA in our South East Asian cohort. More functional experiments need to be done to find out whether this is causal for PA or whether the SNP is in linkage disequilibrium with the actual functional causative SNPs. Once the functional SNP is known, identification of these germline variants in asymptomatic family members would allow early screening of PA to be offered and potentially provide novel drug targets to treat the disease.
References: 1Timberlake et al., Curr Opin Nephrol Hypertens. 2001 Jan;10(1):71-9. 2MacKenzie et al., Int J Mol Sci. 2017 Mar 7;18(3). pii: E579. 3Teo et al., Genome Res. 2009 Nov;19(11):2154-62.
SUN-622 The Risk of Hip and Non-Vertebral Fractures in Diabetes: A Systematic Review and Meta-Analysis Update
Authors: Vilaca Tatiane , Schini Marian , Harnan Susan , Poku Edith , Cummings Steven R , Eastell Richard 
Published: May 2020

Abstract
Background Previous meta-analyses have reported an increase in the risk of hip fractures in diabetes, but the risk of non-vertebral fractures has not been investigated. In addition, it is not known how the risk of fractures is affected by age, body mass index, diabetes duration and insulin use. To investigate these features, we conducted a meta-analysis on the risk of hip and non-vertebral fractures in diabetes. MethodsWe selected a previously published review to be updated. Medline, Embase and Cochrane databases were searched in March 2018 and an update conducted in March 2019 (Pubmed) using relevant MeSH and free text terms such as “diabetes”, “hyperglycaemia” and “fracture”. We selected observational studies with data on the risk of fractures in adults ολδερ τηαν 18 years old with diabetes compared to people without diabetes. Study quality was assessed using the Newcastle Ottawa Scale. We used the random-effects model to calculate the risk estimates and 95% confidence intervals.Results Forty-nine studies were included. Forty-three studies were included in the hip fracture analysis, 40 cohorts and 3 case-control studies, reporting data from 17,575,873 participants, 2,387,899 with diabetes and 321,720 fractures. Eighteen studies reported the risk of fractures in two or more sites and were included in the non-vertebral fracture risk analysis. All but one study were cohorts. These studies reported data from 2,982,622 participants, 414,195 with diabetes and 185,363 fractures. In both analyses, age varies from 20 to 100 years old, including both type 1 and type 2 diabetes. Overall, the study quality was judged to be moderate to good.We found a significant increase in the risk of fracture in diabetes both for hip (RR 1.52, 95% CI 1.42-1.63) and for non-vertebral fracture (RR 1.20, 1.14-1.27). The increase in the risk was greater for insulin users and longer duration of diabetes, at both sites. At the hip, the risk was higher in the younger population, women, and those with T1D. ConclusionThere was an increase in the risk of hip and non-vertebral fractures in diabetes. Although the mechanisms are not established, patients with type 1 diabetes were the population at higher relative risk. The evidence suggest that the skeleton should be considered a site for diabetic complications.
MON-386 Determining Vitamin D Status: Analytical Variability Between Available Assays
Authors: Wahab Azni Lihawa Abdul , Schneider Hans Gerhard 
Published: May 2020

Abstract
Clinical interest to evaluate serum 25-hydroxyvitamin D[25(OH)D] to assess Vitamin D status in health risks continue to increase exponentially over the last decade. Variability of 25(OH)D measurements remains controversial despite the international initiative Vitamin D Standardization Program (VDSP) to standardise the assays. The aim of the present study was to examine the correlation of 25(OH)D concentrations measured by different assays. We measured 25(OH)D using the new Abbott Alinity and DiaSorin LiaisonXL chemiluminescence immunoassays against the National Institute of Standards and Technology (NIST)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The immunoassay method were compared with the LC-MS/MS using Passing-Bablok regression and Bland-Altman analysis. Common 25(OH)D cut-point for classification of vitamin D deficiency was used to compare the different assays.
125 adult serum samples were randomly selected and measured 25(OH)D levels ranged between &lt;10 nmol/L to 290 nmol/L as determined by LC-MS/MS. Compared to the LC-MS/MS, both immunoassays demonstrated strong positive relationship based on Passing-Bablok regression analysis. The results were as follows: Abbott Alinity = 0.85x + 1.29nmol/L, 95% CI: -2.39 to 5.03 (r=0.94); DiaSorin LiaisonXL= 0.74x + 2.54nmol/L, 95% CI: -2.53 to 6.18 (r=0.91).
Despite apparent good correlation, the overall mean bias was -12.6% for Abbott Alinity and -24.4% for DiaSorin LiaisonXL assays. A higher percentage of patients were classified as vitamin D deficient (25(OH)D &lt;50 nmol/L) using DiaSorin LiaisonXL (53%) followed by Abbott Alinity (49%), when compared with LC-MS/MS (34%). Using 25(OH)D ≥ 50nmol/L as “adequate” determined by LC-MS/MS method, 22% (18/82) and 28% (23/82) of patients were classified as “deficient” when analysed on Abbott Alinity and DiaSorin LiaisonXL respectively.
Clinician should be aware of the inter-method variability among different Vitamin D assays despite standardization efforts. These differences could be due to cross-reactivity with 25(OH)D2 and vitamin D metabolites, such as 24,25(OH)2D and epimeric forms. 3-epi-25(OH)D is not separated chromatographically by the LC-MS/MS method used in this study. Therefore, the negative bias observed might be due to interference from the 3-epi-25(OH)D, whereby clinical significance is uncertain. It is present in low concentrations in adult human serum, 1 but seen in significant amounts in neonatal serum.2 It is advisable to monitor serum 25(OH)D level following treatment in the same laboratory.
1. Lensmeyer G, et al. The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum. JCEM 2012; 97: 163–8.
2. Singh RJ, et al. C-3 epimers can account for a significant portion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. JCEM 2006; 91: 3055-61.
MON-126 Telemedicine Interventions for Treatment of Diabetes Mellitus in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Correia Jorge César , Meraj Hafsa , Teoh Soo Huat , Waqas Ahmed , Pataky Zoltan , Golay Alain 
Published: May 2020

Abstract
Diabetes mellitus (DM) is associated with significant morbidity, mortality and poor quality of life. It also has substantial social and financial implications because over 75% of patients with DM live in low- and middle-income countries (LMIC). In this context, it is often opined that diabetes care can be improved by employing telemedicine interventions. The present systematic review and meta-analysis aims to estimate the clinical effectiveness of telemedicine in improving biochemical and treatment adherence outcomes related to DM and provide the certainty of evidence for these interventions. Using a pretested search strategy, nine academic databases were searched from their inception to August 2019: Web of Science, PubMed, Medline, Global Health Library, Cochrane Central Register of Controlled Trials (CENTRAL), New York Academy of Medicine (NYAM) and Popline. We only included RCTs and cluster RCTs testing the effectiveness of tele-medicine-based interventions in type 1, 2 and gestational diabetes in LMIC. Risk of bias in the included RCTs was assessed using the Cochrane tool for assessment of risk of bias in randomized controlled trials. A series of meta-analyses for each individual outcome was run using random effects analyses. Certainty of evidence for these interventions was assessed using the GRADE guidelines. A total of 22 studies describing 23 interventions were included. We identified five modes of interventions delivered using telephone calls (n=6), SMS (n=5), telemetry (n=5) web-based systems (n=3) and smartphone apps (n=3). Major strategies included health record keeping, follow ups, reminders, psychoeducation, glucose monitoring, monitoring prompts, alerts and online consultations Overall, a significant treatment effect was seen among outcomes of HbA1c (SMD=-0.30, 95% CI= -0.42 to -0.17, n=6548, I2= 80.21%) and fasting blood sugar levels (SMD=-0.17, 95% CI= -0.32 to -0.01, n=4709, I2=60.49%), self-efficacy (SMD= 1.94, 95% CI= 1.31 to 2.58, n=626, I2= 95.99) and treatment adherence (SMD= 1.16, 95% CI= 0.78 to 1.54, n=437, I2= 84.8%). A marginally significant effect was seen in improvement of knowledge regarding diabetes (SMD= 0.66, 95% CI= -0.006 to 1.33, n=1345, I2= 93.38%). No significant treatment effect was seen in outcomes of serum triglyceride levels (SMD= -0.02, 95% CI= -0.18 to 0.14, n= 1535, I2=2.98%), serum total cholesterol levels (SMD= -0.05, 95% CI= -0.20 to 0.09, n= 4862, I2=66.45%) and BMI (SMD= -0.03, 95% CI= -0.13 to 0.07, n= 5372, I2=41.78 %). Telephone calls and SMS based telemedicine interventions yielded the highest treatment effects when compared with telemetry and smartphone apps-based services. Although telemedicine was found to be effective in improving several DM related outcomes, the certainty of evidence was downgraded to very low due to substantial heterogeneity, publication bias and risk of bias.
SUN-909 A Unique Presentation of Multiple Endocrine Neoplasia (MEN) Type 1 Mosaicism Caused by a Novel c.124G&gt;A Variant in the MEN1 Gene
Authors: Drummond Russell Sinclair , Harte Rachel , Hilmi Omar , Currie Gemma , Hughes Kate , McManus Frances , Carty David Martin 
Published: May 2020

Abstract
The MEN1 gene is positioned on the long arm of chromosome 11 (11q13) and results in the production of menin. A classical tumour suppressor gene; the spectrum of reported germline MEN1 mutations occur throughout the gene with no strong genotype/phenotype relationship. Mosaicism is extremely rare, a recent report citing only 2 mosaic cases by next generation sequencing1. We describe a 43-year-old female with MEN1 mosaicism associated with parathyroid adenoma and probable gastrinoma.
Our patient initially presented with nephrolithiasis and nephrocalcinosis alongside biochemistry of primary hyperparathyroidism. Imaging confirmed a right lower pole parathyroid adenoma and the lesion was removed, pathology confirming the diagnosis (July 2018). Post operatively she remained hypercalcaemic. Repeat imaging suggested a further right sided culprit lesion.
One year previously (August 2017) she was admitted with a perforated duodenal ulcer within the first part of the duodenum (D1), ascribed to ibuprofen use, requiring surgical repair. Whilst awaiting repeat parathyroid surgery she represented with a further duodenal ulcer and perforation (February 2019) this time in the second part of the duodenum(D2). A second parathyroidectomy was performed and genetic investigations were instigated, given the presence of classical MEN1 phenotype. Again, pathology was consistent with a parathyroid adenoma (March 2019).
DNA was extracted for next generation sequencing which revealed mosaicism with a c.124 G&gt;A variant detected in the MEN1 gene at a level of approximately 15%.
Further investigations have shown normal serum prolactin and pituitary and pancreatic MRI imaging. With no other family members testing positive (parents and 2/3 children) this mutation appears to be a de novo index case. Adjusted Calcium is normal 2.53 mmol/L (2.2-2.6 mmol/L) but serum Chromogranin A is elevated (2620 µg/L (ref range &lt;95 µg/L)).
The c.124 G&gt;A variant predicts an amino acid substitution p.(Gly42Ser) in menin structure, an amino acid change previously associated with MEN12. Given the paucity of MEN1 mosaicism reported within the literature with the presence of the two cell lines and only 15% mosaicism close monitoring will be crucial to determine the genotype/phenotype relationship in our patient.
1 Choppin et al 2019 Eur J Endocrinol 1; 180(2):L1-L3
2 Itoh et al 2017 Clin Pediatr Endocrinol 26;25-28
OR30-01 Real-World Minimed™ 670G System Use and Glycemic Outcomes of Pediatric and Adult Individuals Living with Type 1 Diabetes (T1D) in the United States
Authors: Vigersky Robert Alan , Stone Michael , Agrawal Pratik , Zhong Alex , Velado Kevin , Cordero Toni , Shin John 
Published: May 2020

Abstract
Introduction: The MiniMed™ 670G system was FDA-approved in 2016 for adults and adolescents ≥14yrs, and in 2018 for children ages 7-13yrs with T1D. Since then, use of the system has grown to over 180,000 people in the U.S. The glycemic control benefits of real-world MiniMed™ 670G system Auto Mode use in the U.S. were assessed. Methods: System data (aggregated five-minute instances of sensor glucose [SG]) uploaded from March 2017 to July 2019 by individuals (N=118,737) with T1D and ≥7yrs of age who enabled Auto Mode were analyzed to determine the mean % of overall time spent &lt;54mg/dL/&lt;70mg/dL (TBR); between 70-180mg/dL (TIR); and &gt;180mg/dL/&gt;250mg/dL (TAR). The impact of Auto Mode was further assessed in a sub-group of individuals (N=51,254) with, at least, 7 days of SG data for both Auto Mode turned ON and turned OFF. The % of TIR, TBR and TAR, and the associated glucose management indicator (GMI) were evaluated for the overall OFF (2,524,570 days) and ON (6,308,806 days) periods, and across different age groups. Results: System data TIR was 71.3%; TBR was 0.4% and 1.9%, respectively; and TAR was 26.8% and 6.2%, respectively. User-wise data of Auto Mode OFF versus ON showed a mean of 70.3% of the time spent in Auto Mode, that TIR increased from 60.9% to 69.9%; and that both TBR and TAR decreased. For those 7-13yrs (N=1,417), TIR increased from 48.7% to 61.5%; TBR increased from 0.5% to 0.6% and from 2.0% to 2.2%, respectively; and TAR decreased from 49.3% to 36.3% and from 20.5% to 13.0%, respectively. For those 14-21yrs (N=4,194), TIR increased from 51.0% to 61.5%; TBR decreased from 0.7% to 0.6% and from 2.3% to 2.0%, respectively; and TAR decreased from 46.7% to 36.5% and from 18.5% to 12.5%, respectively. For those ≥22yrs (N=45,643), TIR increased from 62.2% to 70.9%; TBR decreased from 0.7% to 0.5% and from 2.6% to 1.9%, respectively; and TAR decreased from 35.2% to 27.3% and from 9.9% to 6.3%, respectively. The mean GMI decreased by 0.23% (overall), 0.48% (7-13yrs), 0.35% (14-21yrs), and 0.22% (≥22yrs), respectively, with Auto Mode ON versus OFF. Discussion: In over 6 million days of real-world MiniMed™ 670G system Auto Mode use in the U.S., TIR of a large pediatric and adult population with T1D improved by 9% compared to when Auto Mode was OFF, which was comparable to or exceeded the TIR observed in the smaller pivotal trials. These results further support outcomes of the pivotal trials and increased glycemic control with system use.
SAT-439 Thyroid Ultrasound Reports and Thyroid Function Tests in Florida Firefighters: Data from the Firefighter Cancer Initiative
Authors: Casula Sabina , Solle Natasha Schaefer , Caban-Martinez Alberto , Kobetz Erin 
Published: May 2020

Abstract
Background: Several epidemiological studies suggest firefighters are at risk for numerous site-specific malignancies, including thyroid cancer. However, it is not well known if chronic exposure to carcinogenic compounds or radio frequency radiation, increases the rate of thyroid nodules and/or affect the thyroid function in this high-risk occupational group. To gain a better understanding, we examine the rate of thyroid nodules and assess the presence of thyroid dysfunction in a sample of Florida firefighters. Methods: A cross sectional study design was conducted to evaluate 103 firefighters, with not known thyroid disease, who were assessed by a physician-performed, real time ultrasound protocol followed by a blood collection to evaluate TSH, Free T4, T4, T3, TPO and Tg antibodies. Additional data such as gender, age and race were also collected and analyzed. Results: Among the 103 firefighters who completed the study protocol, the sample mean age was 39.4+-7.6 years (range 26 to 60) 88.4% male, 87.6% Caucasian and 65% Hispanic. 8.7% of men and 33% of women were found to have thyroid nodules. Of the 20 participants with thyroid nodules only three nodules were above 1 cm, and only one was classified as high risk and met criteria for fine needle aspiration. 8.7 % of men and 33% of women were found to have +TPO antibodies. 18.6% of men and 25% of women were found to have isolated low T3. Conclusion: The prevalence of thyroid nodules, and of Hashimoto thyroiditis, among Florida firefighters, is comparable with the rate found in the general population based on previous epidemiological data. Surprisingly, we found that a significant number of subjects have isolated low T3. In this study, the level of Free T3 was not assessed, however since T4 was normal, we can conclude that the low T3 was not related to a low level of TBG. Low T3 is usually found in systemic illness and has been postulated as a prognostic factor in cardiovascular disease, chronic fatigue syndrome, survival after stroke, and Alzheimer’s disease. The clinical significance and the prevalence of Low T3 in a healthy population has not been well described. Further research is needed to fully understand the significance of this finding.
SUN-903 Insulinoma - a Tricker Diagnosis When Some Pieces Are Missing
Authors: Silva Maria Manuel 
Published: May 2020

Abstract
Insulinoma is a rare pancreatic neuroendocrine tumour that secretes insulin, causing hypoglycemia. Because of the nonspecific symptoms, the diagnosis could constitute a challenge. Early detection is important to prevent serious consequences.
A 31-year old woman was admitted for prolonged fasting test. She had no relevant past medical or surgical history till eight months before, when she had an episode of generalized tonic-clonic seizure with loss of consciousness. At this time, she was taken to emergency, with identification of a hypoglycaemia of 33 mg/dL. Unfortunately this was undervalued and she was discharged with an appointment on a neurologist. After evaluation, she did an EEG, which was normal, and blood tests that identified a fasting glycemia of 50 mg/dL. By recommendation of her general practitioner, she began to monitor her glycemia during the day, identifying multiple glycemia &lt;50mg/dL – in fasting and post-prandial period. After the first generalized seizure, she had multiple seizures, always associated with hypoglycaemia. During the night she had to wake up every two hours to eat, in order to prevent hypoglycaemia. Moreover, in the last 6 months, she augmented 12 Kg. She also described two episodes of behavioural changes with confusion and speech alteration.
She wasn’t under any medication that could be associated with hypoglycemias. Previous records showed she had a fasting glycemia of 50 mg/dL two years ago. When she was admitted to our department, besides she had eat one hour before, she had glycemia &lt;55 mg/dL. Blood tests showed glucose level=22 mg/dL, insulin=39 μU/mL (normal range 2.6-24.9 μU/mL), C-Pep=0.90 ng/mL (normal range 1.1-4-4 ng/mL). Plasma B-hydroxybutyrate was negative. After Glucagon EV, glucose level increase to 53 mg/dL (&gt;25 mg/dL). We also evaluated cortisol and growth hormone that were normal. Abdominal computed tomography scan with contrast demonstrated a well-defined hypervascular lesion involving pancreas tail. Abdominal MRI was also performed showing a hypervascular lesion involving pancreas tail with 11x21mm. Laparoscopic surgery to enucleate the lesion was made. Pathological evaluation revealed a well-differentiated neuroendocrine tumour (positive staining for synaptophysin, cromogranin and insulin) measuring 0.3 cm. The diagnosis of pancreatic insulinoma was confirmed. After surgery, the glucose level increased to the normal range. The patient is currently in 6 months follow-up with a good evolution.
The diagnosis of insulinoma requires high suspicion. In this case, the patient didn’t have the typical insidious neurogenic symptoms. There is a need to value neuroglycopenic symptoms associated with hypoglycemia, otherwise serious consequences can occur.