bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-LB305 The “Normal” Hormonal Levels in Athletes: Should Reference Ranges Be Adapted for the Physically Active Population?
Authors: Cadegiani Flavio , Abrao Tatiana P C , da Silva Pedro Luiz H , Kater Claudio E 
Published: May 2020

Abstract
Background:Despite the growing number of physically active subjects, including elite and amateur athletes, little is known regarding metabolic and hormonal chronic adaptations to exercises. While the elucidation of the hormonal and metabolic physiological adaptations to physical activity is of emerging importance, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study have serendipitously unveiled the existence of multiple metabolic and endocrine physiological changes in male athletes, including chronic increase of testosterone with concurrent physiological increase of estradiol, enhanced GH and cortisol responses to stimulations,andincreased catecholamines, basal metabolic rate, fat oxidation, and hydration status. These findings were uncovered due to a novel methodological design in which athletes affected by overtraining syndrome (OTS) were compared to a two control groups, of healthy athletes (ATL) and healthy non-physically active controls (NPAC). Since none of the parameters were directly dependent on exercise or performance, differences between these two groups were unexpected. From the fact that several parameters were shown to be different between ATL and NPAC, we realized that the use of the reference ranges for general population to analyze results in athletes may potentially under- and over-diagnose a wide range of conditions. Our objective is therefore to determine whether athletes should be biochemically evaluated through specific adapted ranges, and propose preliminary adaptations in these ranges. Methods: A systematic review on the literature on endocrine and metabolic adaptations to exercise was performed, as well as a thorough analysis of the seven arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. Results:Multiple reference ranges were shown to be inaccurate for athletes. Among the parameters that should be adapted for athletes, and their respective adaptedranges include: 1. Cortisol response to an insulin stimulation test (ITT) (&gt; 20.5 μg/dL); 2. GH response to an ITT (&gt; 12 μg/L); 3. Prolactin response to an ITT (&gt; 22 ng/mL); 4. Salivary cortisol at 8AM (&gt; 450 ng/dL); 5. Total testosterone (&gt; 450 ng/dL); 6. Estradiol (25-45 pg/mL) - and testosterone-to-estradiol ratio maintained &gt; 13.7; 7. Total nocturnal urinary catecholamines (&gt; 220 μg/12h); 8. Resting lactate (&lt; 1.0 nMol/L); 9. Measured-to-predicted basal metabolic rate (BMR) (&gt; 105%); 10. Fat oxidation (in relation to total BMR) (&gt; 50%); and 11. Hydration status (body water &gt; 62% of total body weight). Conclusion: Analysis of biochemical parameters in athleted should be interpreted with cautious, particularly hormonal and metabolic parameters, once many parameters likely undergo adaptive changes when under physical activity. Preliminary adaptations for the ranges have been proposed.
SAT-LB138 The LncRNA Growth Arrest Specific 5 Regulates Cell Survival via Distinct Structural Modules With Independent Functions
Authors: Frank Filipp , Kavousi Nadieh , Bountali Aikaterina , Dammer Eric , Mourtada-Maarabouni Mirna , Ortlund Eric 
Published: May 2020

Abstract
The growth arrest-specific 5 (gas5) gene encodes a long non-coding RNA (lncRNA) that is required for normal growth arrest, slows down the cell cycle, controls apoptosis, and is required for the inhibition of cell growth by mTOR inhibitors such as rapamycin. In agreement with this role in regulating cell proliferation, Gas5 expression is reduced and acts as a tumor suppressor in numerous cancers, including B-cell lymphoma and leukemia. At its 3’ terminal end (nucleotides 546-566) Gas5 contains a predicted stem-loop structure that specifically interacts with steroid receptors (SRs) and blocks DNA-dependent steroid signalling. In steroid-sensitive cancer cells such as prostate cancers this SR binding motif is responsible for Gas5 effects on cell growth. This is not true in other cell types, however, where proliferation is not strongly dependent on SR signaling (e.g. leukemic T cells). Therefore, other regions in Gas5 must be active and use different mechanisms to regulate cell survival. We have used SHAPE chemical probing to analyze the secondary structure of Gas5 in vitro and in cellulo. We find that the secondary structure of endogenous Gas5 resembles that of in vitro transcribed Gas5 RNA. The molecule contains three separate structural modules: a 5’ module with low secondary structure content, a highly structured core module, and the SR binding module, which forms separate from the rest of the molecule close to its 3’ end. Functional studies in leukemic T cells show that the 5’ module mediates Gas5’s role in inhibiting basal cell survival and slowing the cell cycle, whereas the core module is required for mediating the effects of mTOR inhibition. These results confirm that the Gas5 structural modules function independently in cells and each module acts under different cellular conditions, likely using different molecular mechanisms. RNA pull-downs from cell lysates using the identified modules and full-length RNA identified proteins preferentially associated with each module. Proteins preferentially associated with the 5’ terminal region are enriched in splicing and RNA processing factors. The structured central region preferentially interacts with proteins involved in chromosome organization such as the SWI/SNF family of nucleosome remodeling complexes.
SUN-LB64 Urine Phosphoethanolamine Is an Underutilized Biomarker for Hypophosphastasia
Authors: Shajani-Yi Zahra , Ayala-Lopex Nadia , Black Margo , Dahir Kathryn McCrystal 
Published: May 2020

Abstract
Hypophosphatasia (HPP) is a rare disease caused by a loss-of-function mutation in the ALPL gene leading to a deficiency in the tissue-non-specific isoenzyme alkaline phosphatase (ALP) and excess of extracellular inorganic pyrophosphate (PPi) and pyridoxal 5’phosphate (PLP). Patients with HPP have a widely variable clinical phenotype, from neonatal seizures and hypomineralization to isolated dental or joint disease in adults. Patients present with ALP activity levels below their age-adjusted reference interval and elevations in PLP. This variable clinical phenotype leads to significant diagnostic challenges, particularly in those with minor disease manifestations. Biomarkers for diagnosing HPP and monitoring patients on enzyme replacement therapy (ERT) are limited. Low ALP activity is not specific for HPP; it can be low in other conditions including untreated hypothyroidism, and other skeletal dysplasias. Accurate PLP assessment is limited in patients on ERT due to hydrolysis of the substrate. Phosphoethanolamine (PEA) is a substrate hydrolyzed by TNSALP and elevated levels of PEA may be observed in HPP, supporting the diagnosis of HPP, but have been reported to be non-specific. We hypothesized that urine PEA levels could be used to diagnose HPP and as a surrogate marker for ERT compliance. We performed a retrospective analysis on 83 adult patients (63F: 20M) presenting for investigation or follow-up of HPP from 7/1/2014 to 1/7/2020. Urine was sent to the Children’s Hospital in Colorado for PEA testing. Patients were diagnosed with HPP if they had ALP levels persistently below the age-adjusted reference interval, were positive for an ALPL gene mutation/had a family history of HPP and had musculoskeletal/dental symptoms consistent with the disease. Patients were negative for HPP if ALP was not persistently low, vitamin B6 levels were normal without supplementation, negative ALPL genetic testing results (when available) and no musculoskeletal/dental symptoms. PEA levels were not considered for diagnosis. The following was collected from the EMR: PEA results, diagnosis, and ERT status. PEA levels were higher in patients with HPP not on ERT (median=117.0, N=39) vs. those negative for HPP (median=24.0, N=15, p&lt;0.0001). The receiver operator curve for PEA in diagnosing HPP had an AUC of 0.94 (SE=0.03, p&lt;0.0001). Specificity was 100% at PEA levels &gt;53.5 ng/ml (sensitivity=79.5%) with an NPV of 65.2% and PPV of 100%. Initial PEA values in patients with HPP and not on ERT were higher (median 117.0, N=39) than patients on ERT (median 65.0, N=16, p=0.004). Patients who began ERT had a decline in PEA levels after treatment (mean decrease 68.1%). PEA is a specific diagnostic marker for HPP in patients undergoing investigation for HPP and may be used as a surrogate marker to monitor ERT compliance. Future studies are necessary to evaluate the association between PEA levels and functional performance.
MON-LB100 Novel Paradoxical Markers of Weight Loss: Is the Worse Actually the Better? a Retrospectiveanalysisof 1,567 Patientswith Obesity With Successful Clinical Weight-Loss Approaches
Authors: Cadegiani Flavio , da Silva Pedro Luiz H 
Published: May 2020

Abstract
Background:Obesity is a chronic, multi-factorial, and relapsing disorder that has been reported to be a risk factor to more than 200 diseases, among which the majority is direct- or indirectly triggered by the metabolic abnormalities induced by excessive body fat. Indeed, patients with obesity tend to disclose multiple alterations of metabolic markers, which tend to improve with weight loss. Despite the multiple dysfunctions extensively in this population, only mandatory biochemical exams are usually ordered, likely due to limitations in cost and lack of cost-effectiveness, since the majority of the parameters typically altered in obesity does not drive therapeutic choices or influence in an individual-based evaluation.We developed a protocol for obesity treatment that includes a thorough analysis and follow up of the biochemical parameters of patients with obesity, including more than 50 parameters, for more precise diagnosis and response to treatments. Among these parameters, we identified unexpected changes, including some that would initially be related to increased cardiovascular risk or worse prognosis when in an usual context, but which could peculiarly indicate successfulness of weight loss, since these parameters tend to return to normal levels after a period in the new body weight. Our objective is to identify whether these paradoxical changes in biomarkers are linearly correlated with body weight loss, fat loss, mass loss, or whether they were related to the use of any anti-obesity drug. Methods: In a retrospective cohort of 1,567 patients that underwent a clinical weight loss treatment for obesity in a obesity center (Corpometria Institute, Brasília, DF, Brazil), we performed a linear association analysis between body weight and body fat (air displacement pletismography - Bod Pod, CosMed, USA) and 65 parameters, including hormonal, metabolic, inflammatory, and immunologic parameters. We also adjusted for the use of anti-obesity drugs. Results: Homocysteine and triglycerides were identified to increase linearly according to the amount of weight loss (r = -0.77) and fat loss (r = -0.85), but not due to the use of any drug. Folic acid decrease was directly related to fat loss (r = 0.81). Additional findings include more significant decrease of ApoB, compared to LDLc, decreases of GGT, ALT, CRP, ESR, neutrophils, ferritin, fibrinogen, PTH, free T3, uric acid, a and temporary decrease of ApoA and HDLc, all related with body fat loss. Conclusions: Increase of homocysteine resulted from decreased folic acid metabolism, and increased triglycerides may be indirect markers of lipolysis, as no other plausible mechanism could explain these findings.
SUN-299 Flash Glucose Sensor Monitoring for Patients with Endogenous Hyperinsulinaemic Hypoglycaemia
Authors: Arshad Muhammad Fahad , Kaluarachchi Vidumini , Iqbal Ahmed , Munir Alia , Newell-Price John D C 
Published: May 2020

Abstract
Flash Glucose Sensor Monitoring for patients with endogenous hyperinsulinaemic hypoglycaemia
Background:
Flash glucose monitoring systems (FGS) have recently been introduced and measure interstitial glucose using an amperometric electrochemical sensor assay, and are increasingly used to provide a convenient means to monitor levels on a minute-by-minute basis over two weeks in ambulatory patients with diabetes. Although continuous glucose monitoring systems have been previously used in patients with insulinoma,(1) to our knowledge, FGS use has only been described once previously in an adult patient with an insulinoma.(2) Here, we describe use of this system in 6 patients with confirmed endogenous hyperinsulinaemic hypoglycaemia, especially for the critical nocturnal period.
Methods and patients:
FGS data obtained over each 2-week monitoring was reviewed in 6 patients seen between 2018 and 2019: 5 had a biochemically proven insulinoma and 1 had Hirata’s syndrome. In 4 patients, follow-up readings were obtained after adjustment of glucose-raising medication: two on octreotide, one on diazoxide and one on diazoxide and dexamethasone.
Results:
Median age was 63 years (range 37–83). In the 4 patients with more than one 2-week FGS assessment comparison between first and last readings demonstrated that the average duration of hypoglycaemia (&lt;4mmol/L) 126, 171, 173 and 282 minutes improved to 46, 128, 30 and 0 minutes, respectively. The percentage of glucose readings below target (&lt;4mmol/L) improved from 8%, 58%, 4%, and 47% to 1%, 39%, 0%, and 0%, respectively. The mean glucose was 5.9, 3.9, 7.8, and 4.4 mmol/L, which improved to 10.9, 5.0, 7.9, and 7.5 mmol/L respectively. The lowest average glucose was nocturnal (22:00-06:00) (5.8, 3.3, 6.5, and 4.1 mmol/L) which showed significant improvement after adjustment of medications (11.3, 4.2, 7.2, and 5.7 mmol/L). At least 2 of these 4 patients had well documented impaired awareness of hypoglycaemia based on diminished classical adrenergic symptoms. Among the two patients who had only one 2-week FGS assessment, one went on to have curative successful surgery and the second patient who had Hirata’s syndrome did not have significant detectable hypoglycaemia.
Conclusion:
FGS is a convenient tool that may be used to monitor and adjust therapy in patients with endogenous hyperinsulinism. In carefully selected patients, FGS may allow domiciliary glycaemic management avoiding the need for hospital admission for monitoring purposes.
References:
1. Munir, Alia et al. “Continuous glucose monitoring in patients with insulinoma.” Clinical Endocrinology vol.68,6 (2008): 912–918
2. Sugawa, Taku et al. “Hypoglycemia Unawareness in Insulinoma Revealed with Flash Glucose Monitoring Systems.” Internal medicine (Tokyo, Japan) vol. 57,23 (2018): 3407–3412
MON-686 Insulin Autoimmune Syndrome as a Rare Cause of Hypoglycemia
Authors: Mokhtar Marwa , Gul Wajiha , Skarulis Monica 
Published: May 2020

Abstract
Background:
Insulin Autoimmune Syndrome (IAS) or Hirata disease is reported more in Asians. We report the case of a patient with acute onset hypoglycemia secondary to IAS.
Case Presentation:
A 64 year old ARAB male physician presented with 2 weeks history of episodic hypoglycaemia with blood glucose (BG) 40–60 mg/dl, unrelated to food and occurring throughout the day. His attacks were associated with sweating, dizziness and palpitations, relieved by intake of juice. He reported 3 kg weight gain since the beginning of his symptoms.
Past medical history revealed hypertension, past HCV infection with negative PCR and history of allergy to sulfa drugs. His medications included bisoprolol 2.5 mg daily.
Physical exam showed no acanthosis nigericans. Laboratory investigations: Normal hepatic, renal and thyroid functions. 72 Hours fasting test was performed. at hour 3, the BG was 2.27 mmol (40.86 mg/dl), insulin &gt; 1000 mU/ml (N: 2.6–24.9), c- peptide 15 ng/ml (N: 1.1–4.4), negative beta-hydroxybutyrate, with good glycemia response to glucagon 1mg. Urine sulfonylurea (SU) screen was negative. Insulin antibodies titre was high 8.9 nmol/L (N: 0–0.02) and Proinsulin &gt;700 pmol/L (N: 3.6–22). MRI Abdomen showed only 3 mm lesion in the pancreatic head, likely a cyst.
During hospitalization, the patient continued to have episodic hypoglycaemia and received dextrose 10% and octreotide injection. Bisoprolol was changed to amlodipine as it may mask his symptoms.
Episodes of hypoglycaemia improved with octreotide but did not resolve completely. Prednisolone 30 mg daily was started with improvement and was tapered slowly after 16 weeks after mild hyperglycemia developed. Repeat work up showed reduction in insulin 67.4 mcunit/ml, C- peptide 2.66 ng/ml and insulin antibody titres to 0.24 nmol/L and remission of hypoglycemia.
Discussion:
Autoimmune hypoglycaemia is rare resulting from insulin antibodies(IAS), or anti-insulin receptor antibodies (Type B insulin Resistance). IAS can be triggered by drugs or viruses including hepatitis C and is associated with autoimmune diseases and hematologic malignancies. the differential diagnosis of hyperinsulinemic hypoglycemia include insulinoma, the presence of extreme levels of insulin, c-peptide and proinsulin and insulin antibodies is diagnostic of AIS. Short-term treatment with steroids was effective in treating hypoglycaemia and careful follow-up is ongoing. If the patient recurs, rituximab will be employed.
References:
1-CHURCH, D., CARDOSO, L., KAY, R. G., WILLIAMS, C. L., FREUDENTHAL, B., CLARKE, C., HARRIS, J., MOORTHY, M., KARRA, E., GRIBBLE, F. M., REIMANN, F., BURLING, K., WILLIAMS, A. J. K., MUNIR, A., JONES, T. H., FUHRER, D., MOELLER, L. C., COHEN, M., KHOO, B., HALSALL, D. & SEMPLE, R. K. 2018. Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome. J Clin Endocrinol Metab, 103, 3845–3855.
SUN-492 Treatment of Uncontrolled Graves’ Disease Reveals Underlying Thyroiditis
Authors: Sheung Nicole , Belalcazar Ligia Maria 
Published: May 2020

Abstract
Thyrotoxicosis is a life-threatening condition that may result from poor adherence to medical therapy. We describe the case of a patient with Graves’ disease and a history of medication non-compliance who presented with tachyarrhythmia and heart failure (HF). His protracted course after weeks of inpatient treatment with thionamides, iodine, resin and beta-blockers, was followed by a dramatic improvement within days of adding steroids, suggesting the presence of concurrent untreated thyroiditis.
Case Description: A 38-year-old man with an 18-month history of known Graves’ disease presented to the endocrinology clinic requesting thyroidectomy. He complained of 3 weeks of worsening palpitations, shortness of breath, bilateral lower extremity edema, and frequent loose stools. History revealed frequent interruption of thionamide and recent discontinuation of propranolol due to patient’s perceived lack of improvement. Physical exam showed a thin male with a large goiter. He was in moderate distress due to tachypnea. He had atrial fibrillation with rapid ventricular rate (A Fib with RVR) but was not in pulmonary edema. Laboratories showed a suppressed TSH (&lt;0.02 mIU/L [0.45 - 4.70 mIU/L]), a free T4 above the level of detection (&gt;6.99 ng/dL [0.78 - 2.20 ng/dL], and a total T3 level of above 781 pg/mL (97.0 - 170.0 ng/dL). Methimazole 30 mg BID and propranolol 40 mg TID were started, followed within a few hours with potassium iodine (SSKI) 3 drops TID. Although the patient’s HF improved and there was down-trending of free T4, he continued to have A fib with RVR. SSKI and propranolol were increased; diltiazem 90 mg QID and cholestyramine 2g BID were later added. Despite aggressive treatment, the patient continued to have intermittent tachyarrhythmia, postponing his planned thyroidectomy for weeks. Dexamethasone 2mg Q8H was then started aiming to further decrease T4 to T3 conversion. Interestingly, within 48 hours of the start of steroid therapy, his free T4 level markedly decreased and was well within the normal range several days later when he underwent a successful thyroidectomy, with no further tachyarrhythmia recurrence.
Discussion: Thyrotoxicosis is aggressively treated given its high mortality rate. Treatment algorithms guide physicians to categorize hyperthyroidism either as the type associated with increased hormone synthesis and secretion or that which results from increased hormone release due to gland destruction. This thought process may lead, as in our case, to a delay in appropriate therapy and an increased risk of disease complications. Furthermore, providers should not assume that the lack of treatment response in a patient with Graves’ disease is the result of medication non-adherence. The possibility of coexisting thyroiditis and the absence of a treatment regimen that effectively addresses both underlying processes may be the actual cause for the lack of clinical improvement.
SAT-561 Effects of Mineralocorticoid Receptor Antagonists on Primary Aldosteronism Screening
Authors: Tezuka Yuta , Turcu Adina 
Published: May 2020

Abstract
Background: Mineralocorticoid receptor antagonists (MRAs) are the mainstay of medical therapy for primary aldosteronism (PA), and MRAs also benefit patients with other forms of resistant hypertension and cardiovascular disorders. MRAs impact the renin-angiotensin-aldosterone system (RAAS), raising concerns regarding the accuracy of PA screening. The rate of false negative and/or false positive screening for PA in patients taking MRAs has not been systematically evaluated. Herein, we assessed the alterations of both renin and aldosterone after MRA initiation in a large cohort of patients with hypertension.
Patients and Methods: We conducted a retrospective cohort study of patients with hypertension seen in a tertiary referral center. We employed our center’s database search engine to identify adults with hypertension who were treated with MRAs. Of these, we included patients who had renin and aldosterone measured both before and after MRA treatment. We excluded patients with adrenal cortical cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. PA screening was considered positive when plasma aldosterone concentration (PAC) was 10 ng/dL, plasma renin activity (PRA) was 1.0 ng/mL/h, and the aldosterone-to renin ratio (ARR) was 20. Mann-Whitney test and Wilcoxon signed rank test were employed to compare independent or paired groups, respectively.
Results: In total, 109 patients (57 women), mean age 55+/-13 years were included. Of these, 40% had confirmed PA (14% unilateral and 26% bilateral); in 38% PA was excluded; and in the remaining 22%, testing for PA was incomplete. On average, patients were on 3 +/- 1.6 antihypertensive agents; 60% of patients were prescribed beta blockers, 49% K+-wasting diuretics and 35% were on K+ supplements. Both PAC and PRA increased after MRA treatment (from 19.0 [12.6, 26.7] to 26.3 [17.2, 36.2]; and from 0.6 [0.10, 0.80] to 1.00 [0.60, 2.80], respectively, p &lt; 0.0001 for both), while ARR decreased from 42.5 [18.5, 109.8] to 24.0 [10.9, 55.5] (p = 0.003). Of 71 patients with positive PA screening at baseline, 31 (43.7 %) no longer met positive screening criteria during MRA therapy. Conversely, 7 of 38 patients (18 %) with negative screening at baseline met criteria for positive PA screening while on MRA treatment, including 5 patients with a PAC &gt; 20 ng/dL along with suppressed renin. The impact on PA screening accuracy remained similar irrespective of the MRA dose, duration of treatment, changes in concomitant antihypertensive drugs, or hypertension type.
Conclusions: Commonly, MRA treatment leads to renin elevation, ARR reduction, and consequential false negative PA screening. In a minority of patients, MRA therapy can be followed by aldosterone elevations asynchronous from renin, possibly via short feedback loops, mimicking PA. Whenever possible, PA testing should be conducted after MRA discontinuation.