bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-741 Salivary Cortisol and Cortisone Measurement Provide a Novel and Non-Invasive Method of Monitoring Medical Therapy in Cushing’s Syndrome
Authors: Manson Megan Elizabeth , Adam Safwaan , Steimer Anna-Elisabeth Minder , Abdullah Noor Rafhati Adyani , Higham Claire Emily , Meredith Suzanne , White Anne , Cottrell Elizabeth Claire , Monaghan Phillip , Keevil Brian George , Trainer Peter James 
Published: May 2020

Abstract
Introduction:
Salivary glucocorticoids (cortisol [SalF], cortisone [SalE]) are collected non-invasively, unaffected by variation in cortisol binding globulin (CBG) and an established tool in the investigation of Cushing’s syndrome (CS). We have previously shown a strong correlation between salivary glucocorticoids and circulating free serum cortisol, better than that with total serum cortisol. Measurement by liquid chromatography with tandem mass spectrometry (LC-MS/MS) permits lower limits of quantification, eliminates cross-reactivity both between cortisol and cortisone, and by metyrapone-induced elevations in 11-deoxycortisol.
Previous studies in CS have demonstrated that a mean (based on 5 samples during a single day) serum cortisol (serumF) of 150-300 nmol/l equates to a normal isotopically calculated cortisol production rate. We report the use of salivary glucocorticoid measurement in metyrapone-treated CS patients undergoing dose titration to achieve a mean serumF of 150-300 nmol/L.
Methods:
Seventeen (11 females; age-range 24-74 years) patients with CS undergoing dose titration with metyrapone were studied on 44 occasions: 15 ACTH-dependent (5 ectopic) and 2 adrenal.
24 healthy male volunteers (HV) were also studied.
Both cohorts had paired serumF and SalE and SalF samples collected at 5 time-points (10:00; 11:30; 13:00; 14:30; 16:00).
Serum and salivary glucocorticoids were measured using LC-MS/MS.
The TR for salivary glucocorticoids was determined from the mean SalE and SalF in HV whose mean serumF (n=20) was in the desired range (150-300 nmol/L). In CS patients the metyrapone dose had been titrated to achieve a mean serumF of 150-300 nmol/L on 14 (out of 44) occasions.
Results:
Mean SalE (r=0.70; p&lt;0.001) and mean SalF (r=0.51; p&lt;0.001) showed a significant correlation with serumF. The TR from HV for mean SalE and mean SalF were 5.8–24.7 nmol/L and 0.6-5.4 nmol/L respectively.
In CS patients, SalE had greater sensitivity (79% vs. 75%) and specificity (80% vs. 57%) in predicting a mean serumF in the TR than SalF.
Conclusion:
We have demonstrated a close correlation between mean SalE and mean serumF in metyrapone treated CS patients. Salivary glucocorticoids within the derived TR were highly predictive for a target serumF. It is unsurprising, due to the effect of CBG on serumF measurements, that the sensitivity and specificity of SalE and SalF are not greater than reported. Consequently, SalE and SalF, as surrogates for free serum F, have the potential to be superior than serumF when assessing adequacy of medical therapy in CS and may permit out-of-hospital monitoring. Further work is required to validate these findings.
SAT-093 Two Cases of Autosomal Dominant Familial Central Diabetes Insipidus: A Novel Variant in Neurophysin II Region of AVP Gene
Authors: Ramirez, Biochemist Pablo , Vaiani Elisa , Marino, Biochemist Roxana Marcela , Perez-Garrido, Biochemist Natalia Isabel , Morales Cintia , Rubio Betty , Rivarola Marco A , Belgorosky Alicia 
Published: May 2020

Abstract
Central diabetes insipidus (CDI) is a disorder of water balance characterized by polyuria and polydipsia owing to partial or complete deficiency of the antidiuretic hormone, arginine vasopressin (AVP). Although non-hereditary causes are the most frequent, Familial CDI forms, due to heterozygous mutations in the AVP gene, have also long been recognized. Inheritance occurs mostly in an autosomal dominant manner with almost complete penetrance. The AVP gene encodes for a 164 aminoacids preprotein: the AVP preprohormone which consists of a signal peptide, AVP hormone (9 amino acidpeptide), Neurophysin II (AVP carrier), and a glycoprotein, Copeptin. The AVP preprohormone, is produced in the hypothalamus sand is targeted to the endoplasmic reticulum (ER) by the signal peptide. After cleavage and processing, the AVP hormone is packaged within protein carrier NPII and are transported by axonal trafficking to the neurohypophysis where they can be stored and secreted.
Structural changes in NPII have been associated with intracellular accumulation of mutant AVP precursors that have been postulated to be cytotoxic and decreased cell viability of vasopressin-producing neuronsin the neurohypophysis.
In this study we describe two index cases from two families of four-generation kindred suspected to have Familial neurohypophyseal diabetes insipidus (FNDI), with absent or barely visibleposterior pituitary by MRI. A water deprivation test was performed in both cases, resulting confirmatory for DI in case 1 while it was inconclusive in case 2.
In both cases, molecular studies revealed a pathogenic variant in heterozygous state in the NPII region of the AVP gene, in case 1 we found a previously reported and well characterized variant p.Cys116Gly, cysteine at codon 116 is involved in disulfide bridge important for the secondary structure of NPII. While in case 2 we found a novel variant, p.Gly45Val, in which all in silico tools predict deletereous, whereas there are a previously reported patogenic variant at the same amino acid residueand in 3D modeling it can be observed that structural and conformational changes occur in binding bridge of NPII.
We are reporting two novel non related familial CDI cases, even though lack of functional studies, the clinical phenotype in each pedigree suggest this diagnosis, and support the genetic counseling.
SUN-207 Modelling Long Term Glucocorticoid-Induced HPA Axis Suppression in Mice
Authors: Romano Nicola , Duncan Peter James , Nolan Oscar , Tissier Paul Roussel Le , Shipston Mike , Chambers Thomas 
Published: May 2020

Abstract
Glucocorticoids are prescribed for &gt;3 months to 1% of the UK population. 10-50% of these long-term glucocorticoid treated patients develop persistent HPA axis suppression associated with mortality and morbidity. We have developed a mouse model of glucocorticoid-induced HPA axis dysfunction to determine the mechanisms resulting in persistent HPA axis suppression.
Experiment 1: 36 C57BL/6 adult male mice received Dexamethasone (DEX,~10µg/day) or vehicle (CTL) via drinking water for 28 days, following which treatment was stopped and tissues were harvested at 0, 7 and 28 days. DEX suppressed waking serum corticosterone at days 0 and 7, recovering by day 28. Adrenal size remained lower 28 days following DEX withdrawal. DEX had no effect on whole pituitary pomc, nr3c1 or crhr1 expression, although avpr1b was increased at day 0. In the adrenal, hsd3b2 and cyp11a1 expression were reduced at time 0; normalising by 28 days.
Experiment 2: 24 POMC-GFP male mice were treated as above. Tissues were collected at day 0 (n=6), 7 (n=3) and 10 (n=3) following withdrawal. Pooled corticotrophs (groups of 3) were isolated by FACS and RNA extracted for qPCR. DEX reduced corticotroph pomc expression at time 0 (x20 fold reduction), with x5 fold suppression at day 7, which recovered with evidence of compensation by day 10. DEX increased expression of avpr1b but not crhr1.
CONCLUSION: 28 days dexamethasone treatment in mice suppresses the HPA axis. HPA suppression is evident 7 days following withdrawal of dexamethasone in the adrenal, corticotroph population and corticosterone production. Further analysis will determine mechanisms for delays in HPA axis recovery.
SAT-041 Testosterone Reduces Atherosclerosis and Plaque Specific Inflammatory Markers in the ApoE-/- Mouse Model
Authors: Bateman Lauren , Dalton Caroline , Maitre Christine Le , Jones Thomas Hugh , Kelly Daniel Marcus 
Published: May 2020

Abstract
Low serum testosterone in men is an established cardiovascular risk factor and epidemiological evidence demonstrates an association between low testosterone and with coronary events. Clinical evidence suggests that testosterone therapy (Tth) can improve key cardiovascular risk factors in men and surrogate measures of atherosclerosis, the chronic inflammatory process underlying cardiovascular disease. Atherosclerotic plaque-specific testosterone actions are not fully understood. The present study investigates the influence of testosterone on mediators of vascular inflammation and plaque burden in an in vivo model of atherosclerosis. ApoE-/- mice were either sham operated, castrated or castrated and received fortnightly intramuscular injections of physiological doses of testosterone (mixed testosterone esters, Sustanon 100) to create 3 experimental groups; normal testosterone, testosterone deficient and testosterone replaced respectively. All groups were fed a high-fat ‘Western’ diet for 16 weeks. Lipid deposition in the aortic root was assessed by Oil Red O as an indication of atherosclerotic burden. Plaque composition was assessed immunohistochemically for indicators of stability including collagen content via Masson’s trichrome, and α-smooth muscle actin (αSMA) as well as markers of inflammation including vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule 1 (E-Selectin), and a pan monocyte/macrophage marker (MOMA2). Testosterone deficient castrated mice had significantly increased lipid accumulation in the aortic root compared to testosterone replete sham-operated littermates (48% intima-media area vs 40%, p&lt;0.05). Tth in castrated mice reversed this effect (39%, p&lt;0.05). Plaque stability was not altered between groups. MOMA2 staining indicated increased infiltration and localisation of monocytes/macrophages in the plaques of castrated mice compared to sham-operated (positive staining (% of plaque) 77% vs 59%, P=0.062) and Tth treatment reduced this (77% vs 63%, P=0.1). Vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression were reduced in castrated mice receiving Tth compared to castrated mice receiving saline (33% vs 46%, p&lt;0.05; and 39% vs 58%, P=0.084 respectively). No significant difference in expression of E-Selectin and αSMA were observed between groups. These findings demonstrate that low testosterone increases aortic root lipid deposition and inflammatory composition in a mouse model of atherosclerosis. Increasing testosterone levels through Tth reduces plaque specific inflammatory markers and atherosclerotic burden. This indicates an anti-inflammatory mechanism by which testosterone can protect against the development and progression of atherosclerosis to reduce cardiovascular risk in men.
SAT-683 A Case of Autoimmune Polyglandular Syndrome Type 2 and Guillain-Barré Syndrome
Authors: Cutler Jason , Brutsaert Erika 
Published: May 2020

Abstract
Background: Autoimmune polyglandular syndrome type 2 (APS2) is defined by the occurrence of two or more autoimmune diseases, with Addison’s disease being most prevalent, and autoimmune thyroid disease and type 1 diabetes mellitus also being common. Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy that is also autoimmune in nature, resulting in ascending muscle weakness or paralysis.
Clinical Case: A 49 year old female with past medical history of vitiligo, subclinical hyperthyroidism, and Guillain-Barré syndrome (GBS) presented to our institution with fatigue, nausea, vomiting, polyuria, and polydipsia. She had no history of diabetes. Her history was also significant for GBS, diagnosed 5 months prior to her current admission. She was treated with intravenous immunoglobulin (IVIG) and had partial improvement of motor impairment. On exam, she was noted to have dry mucous membranes, epigastric tenderness, and patches of hyopigmented skin. Laboratory studies were consistent with diabetic ketoacidosis, and she was admitted to the ICU for management.
Labs from 5 months prior were significant for a HbA1c of 6.4% (4.0-5.6%), TSH &lt;0.002 mIU/L (0.350-4.7 mIU/L), total T3 154.9 ng/dL (79-149 ng/dL), and free T4 1.7 ng/dL (0.7-1.9 ng/dL), and elevated thyroid stimulating immunoglobulin.
During the current admission, HbA1c had risen to 13.6%, C-Peptide 0.6 ng/mL (1.1-4.4 ng/mL) and GAD-65 antibody &gt;250 IU/mL (&lt;5 IU/mL), consistent with a diagnosis of late-onset type 1 diabetes. Repeat thyroid function tests (TSH &lt;0.002 mIU/L, total T3 74 ng/dL, and free T4 1.2 ng/dL), were consistent with subclinical hyperthyroidism. A 21-hydoxylase antibody level was 13 U/mL (&lt;1 U/mL), but cortisol rose appropriately in response to cosyntropin. Based on the patient’s constellation of vitiligo, autoimmune thyroid disease, type 1 diabetes, and elevated 21-hydroxylase antibodies, she was diagnosed with APS2.
Conclusion: We present an unusual case of a patient with APS2, who was diagnosed with type 1 diabetes 5 months after developing GBS and being treated with IVIG. Prior reports demonstrate an association between GBS and other autoimmune diseases, including one case report of GBS in a patient with APS2. HLA DR3 has been associated with APS2, type 1 diabetes, Addison’s disease and Grave’s disease. Its association with GBS is less clear, although HLA DR3 was increased in one Mexican cohort with GBS. This case report adds to the literature suggesting an association with GBS and other autoimmune diseases, specifically, with APS2.
References:
Jin PP, Sun LL, Ding BJ, Qin N, Zhou B, et al. (2015) Human Leukocyte Antigen DQB1 (HLA-DQB1) Polymorphisms and the Risk for Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis. PLOS ONE 10(7): e0131374
Melmed, S., Polonsky, K. S., Larsen, P. R., & Kronenberg, H. (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier
SUN-694 Case Study of Nonalcoholic Steatohepatitis Reversibility in Type Two Diabetic Patient with Weight Loss Using Liraglutide
Authors: Shaghouli Amna Ali , Aranky Rola 
Published: May 2020

Abstract
Introduction Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease.1 NAFLD prevalence is likely to be between 75- 100% in the morbidity obese. Where Nonalcoholic steatohepatitis (NASH) in turns develops in 30% of patients with NAFLD. Obesity prevalence in Kuwait is estimated to be 39% for adults male and 52% for adults females.2 No pharmacotherapy is approved for NAFLD treatment, and the basis treatment is lifestyle modifications focusing on body fat loss.3 A study showed that may take 10% or more weight loss to have an impact on NASH Activity Scores as assessed by liver biopsy. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are approved for the treatment of T2D and obesity and have also been shown to reduce liver inflammation and fibrosis.3
Methods A 54 years old male presented to our clinic with a history of hypothyroidism, diabetes with Hemoglobin A1C (HbA1c) of 7%, hypercholesterolemia and overweight with Body Mass Index (BMI) of 27.6 kg/m2
Patient’s investigations showed high Gamma-glutamyl transferase (GGT) and ferritin level, and due to his abnormal liver function test patient was referred for abdominal ultra sound that showed fatty liver disease. With a high NAFLD score, he was referred for Fibroscan that showed fibrosis score of F3; which indicates a sever liver scarring.
GLP-1 RA was started for weight management and a better glycemic control in a setting of multidisciplinary team, including endocrinologist, diabetes educator, dietitian and a physical trainer.
Results In a six months’ period of time, patient was able to lose 15.3% of his total body weight, with better glycemic control of HbA1c of 5.6% from 7% and his repeated Fibroscan showed improvement in his score from F3 to F0 with other clinically important outcomes.
Conclusion GLP-1 RA seems to be safe to use for patients with NASH, and it might have benefits of reversing fibrosis in addition to other benefits such as weight reduction and HbA1c improvement.
References 1- Babusik P, Bilal M, Duris I. Nonalcoholic fatty liver disease of two ethnic groups in Kuwait: comparison of prevalence and risk factors. Medical Principles and Practice. 2012;21(1):56-62.
2- Jamal MH. The Status of Organ Transplantation in Kuwait.
3- Seghieri M, Christensen AS, Andersen A, Solini A, Knop FK, Vilsbøll T. Future Perspectives on GLP-1 Receptor Agonists and GLP-1/glucagon Receptor Co-agonists in the Treatment of NAFLD. Frontiers in endocrinology. 2018;9.
SAT-076 Hypophosphatemic Rickets Secondary to Elemental Formula Use - Report on Two Cases
Authors: Braz Délia Oliveira , Oliveira Renata Santarem , Lopes Fernanda Sousa Cardoso , Pereira Lara , Domingues Alessandra , de Castro Luiz Claudio Goncalves 
Published: May 2020

Abstract
Background: Hypophosphatemic rickets (HR) is usually an inherited disorder, but it may also occur in several clinical settings as an acquired condition due to phosphate absorption and internal distribution issues. Recently it was described the association between the use of the elemental amino-acid based formula (AAF) and HR. Herein we report two male twins presenting this condition.
Clinical case: Two monozygotic preterm (28 weeks + 5 days) brothers, born with extremely low birth weight (895 and 995 grams, -1,4 SDS and -0.9 SDS, respectively), received total parental nutrition from the 1st to the 7th day of life. Afterwards they started oral diet with milk and human milk fortifier FM85 for preventing metabolic bone disease of prematurity. After some weeks they developed abdominal distension, vomiting and hematochezia. Allergy to cow milk protein was suspected and the infants started receiving extensively hydrolyzed milk formula. So, FM85 was suspended and they were put on tricalcium phosphate (12.9%) supplementation from the 4th week of life on. As the gastrointestinal symptoms persisted, the formula was exchanged for elemental formula Neocate at 2 months of age, with improvement of those symptoms.
After the 5th week of life the patients developed hypophosphatemia (2.8 mg/dL, reference 4.8-7.4 mg/dL), hyperphosphatasemia (1,619 IU/L and 2,173 IU/L; reference 70-350 IU/L) and low urinary phosphate excretion, keeping normal calcium and PTH ser um levels. Radiographic skeletal inventory showed under mineralized bones with irregular metaphyseal margins, but no signs of fractures. Calcium and phosphate supplementation doses were increased in attempt to correct the metabolic disturbances, and calcitriol was also started. Nevertheless, hypophosphatemia, hyperphosphatasemia and hypophosphaturia persisted.
At 4 months of age, Neocate was switched to Alfamino, still an AAF. After that, phosphate serum levels went up until normalization and alkaline phosphatase started to decrease. Calcium and phosphate supplementation were decreased to keep their serum levels at the normal range for age.
The boys were then discharged from hospital when they were 4 months old (45 days of life of corrected age), but the family could not afford Alfamino, switching back to Neocate. After that their phosphate serum levels went below normal range again.
Conclusion: To our knowledge, this is the first report on monozygotic twins presenting AAF Neocate-related HR. The underlying mechanisms of Neocate induced hypophosphatemia is still elusive, since its content of phosphate and calcium:phosphate ratio are similar to other AAFs. These cases reinforce the importance of evaluating phosphate metabolism in infants receiving AAF while the pathophysiology of this condition is not entirely understood.
MON-273 Retrospective Analysis of Gonadotropin-Mediated Pubertal Induction in Male Patients with Congenital Hypogonadotropic Hypogonadism (CHH)
Authors: Cangiano Biagio , Goggi Giovanni , Guizzardi Fabiana , Vezzoli Valeria , Duminuco Paolo , Persani Luca , Bonomi Marco 
Published: May 2020

Abstract
CHH is a rare disease characterized by a failure to enter (complete forms) or to complete (partial forms) pubertal development. It has a strong genetic background and it needs a treatment to allow the puberty to complete. In male this goal could be achieved either by the classic testosterone replacement therapy or by the exogenous gonadotropins (Gn) administration which allows both the endogenous testosterone production and the testicular development. So far, only few studies have explored this latter therapeutic approach in inducing the CHH pubertal development and no internationally recognized protocols are available. Aim of this retrospective analysis is to (i) investigate clinical and biochemical predictors of testicular response to Gn-induced puberty in CHH; (ii) study the non-reproductive outcomes of this treatment (height, body proportions) and their determinants. A total of 19 CHH male patients, undergoing two years of Gn-mediated (FSH and hCG) puberty induction started between the ages of 14 and 23 years, were retrospectively evaluated. For each patient clinical history, physical examination, hormonal evaluation, and genetic analysis using Targeted Next Generation Sequencing for CHH genes was performed; 8 patients accepted to perform a semen analysis (SA) at the end of their treatment.Mann Whitney test and multiple regression analysis showed testicular volume after 24 months of Gn-mediated pubertal induction, to be significantly associated with: (i) the presence of cryptorchidism; (ii) the presence of a completely definable genetic cause for the disease; (iii) the presence of a complete CHH form. No significant association was found with the cumulative dose of hCG administered in 24 months. The statistical analyses regarding SA could not find the same associations. Multiple regression analyses investigating the eunuchoid habitus and a measure of the difference of subject’s final height from his target (deltaSDSth), showed a significant association with: (i) age at the beginning of the induction; (ii) the duration of growth during induction; (iii) and (for deltaSDSth) bone age before the induction. Duration of growth during induction resulted to be associated with previous testosterone priming and with partial CHH.In summary, our study confirms cryptorchidism and complete genetic forms of CHH as negative predictors of testicular response probably because they usually affect early phases of life with a complete GnRH deficiency. We also found that the eunuchoid habitus and deltaSDSth are associated not only with delayed treatment, but also with the duration of stature growth during the induction, apparently related to earlier androgenization.