bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR17-07 Retinol Binding Protein 4 Predicts Functional Vascular Disease in Early Postmenopausal Women
Authors: Armeni Eleni , Nigdelis Meletios P , Augoulea Areti , Chondrou Asimina , Rizos Dimitrios , Kaparos George , Alexandrou Andreas , Goulis Dimitrios G , Georgiopoulos Georgios , Stamatelopoulos Kimon , Lambrinoudaki Irene 
Published: May 2020

Abstract
Introduction: The impact of gender on the development of cardiovascular disease has long been recognized. The potential effect of sex-specific cardiovascular risk factors on molecular mediators of oxidative stress has received limited attention and the results remain conflicting.
Hypothesis: To assess the link between retinol binding protein 4 (RBP4) and menopause-specific cardiovascular risk factors, on indices of early subclinical atherosclerosis, in a sample of apparently healthy young, postmenopausal women.
Methods: This cross-sectional study included a total of 123 healthy postmenopausal women, recruited from a University Menopause Clinic. Participating women were, not on hormone therapy, antihypertensive or hypolipidemic treatment and had a menopausal age of up to 10 years. Fasting venous blood samples were obtained for hormonal and biochemical assessment, including levels of RBP4. Sonographical studies were performed on the same day and included carotid-femoral pulse wave velocity (PWV) and calculation of the carotid artery stiffness index (SI).
Major results: Univariate analysis showed that RBP4 values correlated positively with age, total cholesterol, triglycerides, LDL-cholesterol, testosterone-to-estrogen ratio; negatively with circulating estrogen and almost significantly with homocysteine levels. Levels of homocysteine were inversely associated with RBP4 (homocysteine: RBP4 &lt;10.5ng/ml vs ≥10.5ng/ml: 11.2±2.81μmol/L vs 12.52±3.44μmol/L, p-value=0.049 ANCOVA, adjusted for age, BMI, HOMA-IR). Multivariate analysis showed that PWV values were predicted by RBP4 (b-coefficient=0.435, p-value=0.006), age, pulse pressure, homocysteine. S.I. beta was predicted independently by RBP4 levels (b-coefficient=0.324, p-value=0.039). Both models were adjusted for menopausal age, LDL-cholesterol, FEI, smoking, HOMA-IR.
Conclusion: RBP4 levels are linked with measures of local carotid and aortic arterial stiffness, in this sample of healthy postmenopausal women. This association seems to be mediated by higher levels of homocysteine, which may interfere with retinoic acid synthesis. Larger studies are required to further elucidate the significance of our findings.
References
1. Majerczyk M, Olszanecka-Glinianowicz M, Puzianowska-Kuznicka M, Chudek J: Retinol-binding protein 4 (RBP4) as the causative factor and marker of vascular injury related to insulin resistance. Postepy Hig Med Dosw 2016;70:1267-1275.
2. Smolders RG, van der Mooren MJ, Sipkema P, Kenemans P: Estrogens, homocysteine, vasodilatation and menopause: basic mechanisms, interactions and clinical implications. Gynecol Endocrinol 2003;17:339-354.
3. Limpach A, Dalton M, Miles R, Gadson P: Homocysteine inhibits retinoic acid synthesis: a mechanism for homocysteine-induced congenital defects. Exp Cell Res 2000;260:166-174.
MON-653 The Effects of DPP IV Inhibitor on Glycemic Variability in Type 2 Diabetic Patients Treated with Twice Daily Premixed Human Insulin
Authors: Tan Florence Hui Sieng , Tong Chin Voon , Kuan Yueh Chien , Lau Bik Kui , Loh Huai Heng 
Published: May 2020

Abstract
Glycemic variability (GV) is emerging as an exciting therapeutic target for diabetes mellitus (DM) with recent evidences showing association of GV with hypoglycemia risk as well as chronic complications.(1,2) Twice daily human premixed insulin is commonly used in developing countries and Asia for treatment of type 2 DM (T2DM). (3) While more convenient and cost saving, human premixed insulin regime may increase GV due to lesser flexibility and less physiological pharmacokinetic profile. Dipeptidyl peptidase IV inhibitors (DPPIV-I) have been shown to improve GV when used for treatment of T2DM but the effects of DPPIV-I when added on human premixed insulin is limited. We therefore evaluated the changes in GV following addition of DPP IV-I among T2DM patients treated with premixed human insulin with or without metformin therapy. This was a prospective study involving adult patients with T2DM on stable doses of premixed human insulin with or without metformin for at least 3 months from two state hospitals in Malaysia. Blinded continuous glucose monitoring (CGM) were performed at baseline and following 6 weeks of adding Vildagliptin to their insulin regime. A total of 12 patients were recruited (50% male). Mean (SD) age was 55.8 (13) years with mean duration of disease of 14 (6.6) years. The addition of Vildagliptin significantly reduced GV indexes including SD 2.98 (1.17) to 2.33 (0.82), p=0.017; MAGE 6.94 (2.61) to 5.72 (1.87), p=0.018; MAG 1.60 (0.76) to 1.23 (0.48), p=0.009 and M Value 13.96 (13.01) to 6.52 (7.45), p=0.037. In addition there were improvements in terms of parameters for glycemic control. Time spent in optimal glycemic range (4-8 mmol/l) improved from 38.33 (19.69) to 58.17 (5.95) %, p=0.001 with reduction in AUC for hyperglycemia from 2.09 (1.73) to 1.06 (1.09) mmol/day, p=0.010. Hypoglycemia events were infrequent and the reduction in time spent in hypoglycemia [5.92(9.74) to 1.91 (2.54)%, p=0.191] as well as AUC for hypoglycemia [0.03(0.54) to 0.01(0.02) mmol/day, p=0.163] were found although these did not reach statistical significance. We concluded that addition of DPP IV-I to commonly prescribed twice daily premixed human insulin regime in patients with T2DM may improve GV and glycemic control and warrant further exploration.
References
(1) Gerry Rayman. Glycaemic control, glucose variability and the triangle of diabetes care. Br J Diabetes 2016;16(Suppl1):S3-S6
(2) Boris P. Kovatchev. Metrics for glycaemic control - from HbA1c to continuous glucose monitoring. Nat Rev Endocrinol. 2017 Jul;13(7):425-436
(3) Kalra S, Balhara YP, Sahay BK, Ganapathy B, Das AK. Why is premixed insulin the preferred insulin? Novel answers to a decade-old question. J Assoc Physicians India. 2013 Jan;61(1 Suppl):9-11
SAT-005 Investigating the Endocrine Disorders in Women with Menstrual Disturbances in Bayelsa State, Niger Delta Region of Nigeria
Authors: Ezeiruaku Ferdinand Chukwuma 
Published: May 2020

Abstract
Background: Many women in Bayelsa State, South-South Nigeria have been presenting with different menstrual disturbances and some with infertility problems that are associated with abnormal uterine bleeding, amenorrhea, dysmenorrhea, premature menopause (primary ovarian insfficiency) and premature syndrome (PMS). It is recognized universally that menstrual disturbances may accompany and most times, succeed endocrine disorders. Objective: The aim of the study was to investigate the various endocrine disorders associated with women of reproductive age experiencing different menstrual disturbances attending the different specialist hospitals in Bayelsa State, Nigeria. This is with the interest of establishing the different hormone disorders and its prevalence in these women of Bayelsa State. Method: A total of 1852 subjects (women with menstrual disturbances) were randomly selected using a questionnaire design containing the information of age, last menstrual date, degree of irregularity, whether on medication for any infertility problem or preventive measures and have had any form of surgery. Excluded from the study were pregnant women, women above 40 years of age, those on infertility and contraceptive medication. Analyses of the different hormones of the hypothalamic - pituitary- gonadal reproductive axis were measured using Enzyme Linked Immunosorbent Assay (ELISA). Results: From the study, it was observed that the menstrual disturbances were accompanied with female reproductive hormone fluctuations; with a high significant (P&lt;0.005) percentage, 79.93% of the women having one form of the endocrine disorders. The study has shown that 63.17% of the studied subjects had hypoestrogenism, 38.66% had hypergonadotropic hypogonadism and a non significant (p&gt;0.05) 1.35% with hypogonadotropic hypogonadism. Analysis of the results also showed 15.12% of the subjects had hypothalamic amenorrhea, 32.02% with hyperprolactinaemia and non significant value of 1.30% with hypoprolactinaemia. From the study, 10.92% of the women with menstrual disturbances studied in Bayelsa State had hyperthyroidism, 4.71% with hypothyroidism, 3.74% with T3 thyrotoxicosis and 2.37% with TBG excess. Conclusion: This study therefore concluded that a significant number (p&lt;0.05) of women in Bayelsa State, Nigeria with menstrual disturbances are associated with endocrine disorders probably due to life style (diet, obesity), environmental factors and an underlying illness(infections, cancer and polycystic ovarian syndrome).
SAT-213 Parotid Carcinoma Ex Pleomorphic Adenoma Can Produce Ectopic ACTH Too
Authors: Adly Hussein , O’Donnell Benjamin M , Kirschner Lawrence S 
Published: May 2020

Abstract
Background: Ectopic ACTH syndrome accounts for about 14% of Cushing syndrome cases. Small cell lung cancer is the most common cause. A few case reports described ectopic ACTH syndrome in patients with parotid acinic cell carcinoma. Parotid carcinoma ex pleomorphic adenoma is a malignant transformation within a pleomorphic adenoma, which is mostly adenocarcinoma not otherwise specified, but other subtypes can occur.
Clinical Case: A 41-year old man with parotid cancer and hypothyroidism was admitted to the hospital for hypokalemia (2.1 mmol/L, n: 3.5-5 mmol/L). Parotid cancer was diagnosed a year before admission. At that time, he underwent left parotidectomy, and pathology showed carcinoma ex pleomorphic adenoma with areas of acinic cell carcinoma. Despite chemoradiation, he was diagnosed with metastasis in the lungs, for which pembrolizumab was started. Over the two months prior to admission, he gained 20 lb, and developed lower extremity weakness, acne, erectile dysfunction and loss of libido. He was also diagnosed with hypertension and started to have mild hypokalemia. Suspecting hyperaldosteronism, oncology team ordered labs just prior to admission, which showed the hypokalemia of 2.1 mmol/L, hypernatremia (147 mmol/L, n: 133-143 mmol/L), normal aldosterone and renin, and high cortisol (59.12 mcg/dL, n: 3-22 mcg/dL) and ACTH (121 pg/mL, n: 9-50 pg/mL).
In the hospital, potassium was slowly improving despite aggressive replacement, and blood pressure was still elevated despite increasing his lisinopril dose. Screening for Cushing syndrome revealed an abnormal 1 mg dexamethasone suppression test (cortisol 51.9 mcg/dL, n: &lt;1.8 mcg/dL), and high 24-hour urinary free cortisol (6495 mcg/24h, n: 3.5-45 mcg/24h) and midnight salivary cortisol (2610 ng/dL and 4250 ng/dL, n: &lt;100 ng/dL). Cortisol was not suppressed after 8 mg dexamethasone (cortisol 47.85 mcg/dL, pretest cortisol 48.73 mcg/dL) pointing toward ectopic ACTH syndrome. Spironolactone was started and titrated up to 100 mg BID with better control of hypertension and normalization of potassium. Ketoconazole was started at 200 mg TID and increased gradually as outpatient to 400 mg TID within three weeks. A repeat 24-hour urinary free cortisol was done five weeks after ketoconazole was started showing significant improvement (110 mcg/24h, n: 3.5-45 mcg/24h). Potassium requirements remarkably decreased from 80 mEq TID to 40 mEq daily. Of note, chest CT done during hospitalization showed new lung lesions despite treatment with pembrolizumab.
Conclusion: This is the first case of ectopic ACTH syndrome to be described in a patient with parotid carcinoma ex pleomorphic adenoma, though areas of acinic cell carcinoma within the tumor can be the source of ACTH. Hypercortisolism due to ectopic ACTH secretion is usually of rapid onset, and can present with severe hypokalemia. Steroid synthesis inhibitors seem to be an effective therapy.
SAT-742 Characterising the Metabolism, Glucuronidation and Sulfation of C11-oxy C19 Steroids
Authors: Toit Therina Du , Swart Amanda C 
Published: May 2020

Abstract
The metabolism of 11β-hydroxyandrostenedione (11OHA4), a major adrenal C19 steroid, was first characterised in our in vitro prostate models showing that 11OHA4, catalysed by 11βHSDs, 17βHSDs and 5α-reductases, yields potent androgens, 11keto-testosterone (11KT) and 11keto-dihydrotestosterone (11KDHT) in the 11OHA4-pathway [1]. Findings have since led to the analysis of C11-oxy steroids in PCOS, CAH and 21OHD. However, the only circulating C11-oxy steroids included to date have been 11OHA4, 11keto-androstenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11KT, with 11KT reported as the only potent androgen produced from 11OHA4. We have identified higher levels of 11KDHT compared to 11KT in prostate cancer tissue and benign prostatic hyperplasia tissue and serum, with data suggesting impeded glucuronidation of the C11-oxy androgens [2,3]. The assessment of 11KDHT and the inactivation/conjugation of the C11-oxy steroids in clinical conditions is therefore crucial.
We investigated the metabolism of testosterone, 11KT, 11OHT, dihydrotestosterone, 11KDHT and 11OHDHT in JEG-3 placenta choriocarcinoma, MCF-7 BUS and T-47D breast cancer cells, focusing on glucuronidation and sulfation. Steroids were assayed at 1 µM and metabolites were quantified using UPC2-MS/MS. Conjugated steroids were not detected in JEG-3 cells with DHT (0.6 µM remaining) metabolised to 5α-androstane-3α,17β-diol and androsterone (AST), and 11KDHT (0.9 µM remaining) to 11OHAST and 11KAST. 11OHA4 was converted to 11KA4 (12%) and 11KT (2.5%); and 11KT to 11KDHT (14%). In MCF-7 BUS cells, DHT was significantly glucuronidated, whereas 11KDHT was not. 11KAST was the only steroid in the MCF-7 BUS and T-47D cells that was significantly sulfated (p&lt;0.05). In parallel we investigated sulfation in the LNCaP prostate model. Comparing sulfated to glucuronidated levels, only DHT was sulfated, 26%. Analysis showed that C19 steroids were significantly conjugated (glucuronidated + sulfated) compared to the C11-oxy C19 steroids.
As there exists an intricate interplay between steroid production and inactivation, impacting pre- and post-receptor activation, efficient conjugation would limit adverse downstream effects. Our data demonstrates the production and impeded conjugation of active C11-oxy C19 steroids, allowing the prolonged presence of androgenic steroids in the cellular microenvironment. Identified for the first time is the 11OHA4-pathway in placenta and breast cancer cells, and the sulfation of 11KAST. Characterising steroidogenic pathways in in vitro models paves the direction for in vivo studies associated with characterising clinical disorders and disease, which the C11-oxy C19 steroids and their intermediates, including inactivated and conjugated end-products, have highlighted. [1] Bloem, et al. JSBMB 2015, 153; [2] Du Toit & Swart. MCE 2018, 461; [3] Du Toit & Swart, JSBMB 2020, 105497.
SAT-448 Limited Adaptive Response by Deiodinase Enzymes in the Perinatal Hypothyroid Cochlea
Authors: Calderon Maria Uscategui , Sharlin David S 
Published: May 2020

Abstract
Thyroid hormone (TH) is essential for cochlear development and normal auditory function. Considering the importance of TH in mediating cochlear development, understanding the degree to which developing tissues can adapt to perturbations in thyroid hormone signaling is extremely important. The deiodinases (Dio2 and Dio3) are enzymes that tightly control TH availability at the tissue level and have been proposed to function as adaptive mechanisms that maintain tissue TH homeostasis. Dio2 converts thyroxine (T4) to a biologically active ligand triiodothyronine (T3); locally amplifying a T3 signal. Conversely, Dio3 inactivates T3 and T4 by converting these iodothyronines to the inactive metabolites diiodothyronine (T2) and reverse T3 (rT3), respectively. During cochlear development, Dio3 expression is high prenatally while Dio2 expression is low. During the first postnatal week, the expression levels of these enzymes invert, resulting in high expression of Dio2 and low expression of Dio3. Together, the deiodinases control the timing of postnatal cochlear remodeling; suggesting a genetic developmental clock controls TH-mediated cochlear development. Considering the role deiodinases as adaptive mechanisms, it is important to understand whether such a developmental clock can be negated during times of developmental thyroid hormone insufficiency. We hypothesize that the perinatal change in deiodinase expression is controlled by a developmental clock rather than environmental clues and therefore have limited capacity function as compensatory mechanisms in response to low TH during development. To test this, timed-pregnant mice were treated with thyroid gland inhibitors to induced hypothyroidism from gestational day 12.5 until pup sacrifice. A parallel set of untreated timed-pregnant mice served as controls. Cochlea were harvest from control and hypothyroid mice at postnatal (P) ages P1, P5, P10 and P15 for qRT-PCR, and P7 for in situ hybridization. In situ hybridization for Dio2 mRNA demonstrated a striking reduction in Dio2 mRNA in hypothyroid animals compared to euthyroid animals. Additionally, we observed a significant effect of age (p&lt;0.001) and an interaction between age and treatment (p=0.0035) on Dio2 mRNA levels analyzed by qRT-PCR. Specifically, Dio2 mRNA levels were similar or reduced in hypothyroid animals compared to controls at P1, P5, and P10. This finding indicates that Dio2 mRNA at these ages did not respond in manner consistent with compensation. However, at P15, Dio2 mRNA levels were increased in hypothyroid animals compared to controls; a finding that is consistent with a compensatory mechanism. Taken together, our results suggest that developmental programs in tissues may be dominant over potential compensatory mechanisms and that developing tissues may be more susceptible to perturbations in tissue TH levels due to a reduced capacity to compensate.
SAT-243 Lymphocytic Hypophysitis Mimicking Pituitary Apoplexy in a 27-Year-Old Woman
Authors: Brooks Danielle C , Haber Richard S 
Published: May 2020

Abstract
Introduction:
Lymphocytic hypophysitis is an uncommon inflammatory disorder of the pituitary gland. Peripartum women are most often affected, but it can be seen in a wide range of patients. Patients can present with pituitary dysfunction or mass effect symptoms, making it difficult to differentiate from a pituitary adenoma. Pituitary apoplexy is an acute syndrome due to hemorrhage into the pituitary gland causing headache, visual deficits, and hypoadrenalism. We present a case of a woman with a pituitary mass presenting with symptoms mimicking pituitary apoplexy, in whom surgical pathology later revealed lymphocytic hypophysitis without evidence of hemorrhage.
Clinical Case:
A 27-year-old non-pregnant female presented with severe headaches, nausea, vomiting, and diplopia for four days. A presumed pituitary macroadenoma was diagnosed two years previously during a workup for irregular menses. An emergency evaluation with a CT angiogram of the head showed enhancement at the superior aspect of and surrounding the pituitary gland. MRI of the pituitary revealed an enhancing 17 x 17 mm sellar and suprasellar mass compressing the optic chiasm, without evidence of the normal pituitary posterior bright spot. Visual field testing was normal. She was referred for transsphenoidal resection of the pituitary mass due to persistent headaches, optic chiasm impingement, and suspicion of pituitary apoplexy. Intraoperatively, there was no evidence of hemorrhage. Central diabetes insipidus and hypothyroidism developed in the post-operative period. She was discharged on hydrocortisone replacement therapy (20 mg in the morning, 10 mg in the afternoon). An outpatient random cortisol level of 1.2 mcg/dL (reference: 6.7 - 22.6 mcg/dL) while off hydrocortisone for twenty-four hours confirmed hypocortisolism. Surgical pathology showed moderate lymphocytic infiltrate and focal germinal centers in the adenohypophysis consistent with lymphocytic hypophysitis.
Conclusion:
Although lymphocytic hypophysitis is well-described in the literature, its association with symptoms suggesting pituitary apoplexy has been reported only rarely. This atypical case shows that lymphocytic hypophysitis can present with acute symptoms mimicking pituitary apoplexy. The case highlights the difficulties in recognizing lymphocytic hypophysitis prior to surgery and emphasizes the need to consider the diagnosis in patients presenting with pituitary masses and/or symptoms of pituitary apoplexy.
SUN-643 Potential Contributions of Gut Microbiota-Liver Axis to the Transgenerational Metabolic Reprogramming of Maternal Exercise
Authors: Zhou Liyuan , Xiao Xinhua , Zhang Qian , Li Ming , Yu Miao 
Published: May 2020

Abstract
Background: Early-life overnutrition programs increased risks of metabolic disorders in adulthood. Regular exercise is widely accepted to be an effective measure to maintain metabolic health. However, the transgenerational effects of maternal exercise and the specific mechanism are largely unclear. Aims: Our objective was to investigate whether maternal exercise could alleviate the metabolic disturbances induced by early-life overnutrition in both dams and offspring and to explore the role of gut microbiota-liver axis in mediating the transgenerational metabolic reprogramming. Methods: C57BL/6 females were randomly divided into three groups 3 weeks before mating and during pregnancy: the control group, high-fat group, and high-fat with exercise group (voluntary wheel running training). They received their original diets during lactation. The male offspring had ad libitum access to chow diet from weaning to 24 weeks of age. Glucose tolerance test and serum biochemical parameters were detected. The cecal contents from dams at weaning and 8-week and 24 week of offspring were collected for 16s rDNA sequencing. Hepatic HE staining and transcriptome were performed in adult offspring. Results: The results showed that perinatal high-fat diet resulted in significant glucose intolerance, insulin resistance and lipid profiles disorders in both dams and offspring. Maternal exercise markedly improved insulin sensitivity in dams and metabolic disorders in offspring from young into adulthood, especially the hepatic steatosis. The decrease in harmful bacteria and the persistent enrichment of short chain fatty acid producers from mothers to adult offspring, particularly the genus Odoribacter, were all associated with improvement in metabolism by maternal exercise. In addition, maternal exercise significant upregulated FGF21 and genes involved in the fatty acid oxidation and TCA cycle in adult offspring, which were down-regulated by perinatal high-fat diet and were significantly correlated with the altered microbial species. Conclusion: Overall, maternal exercise could significantly mitigate the detrimental effects of perinatal high-fat diet on metabolism in both dams and male offspring. The continuous alterations in gut microbiota and reprogramming hepatic metabolism might be critical factors in deciphering the transgenerational metabolic benefits of maternal exercise, which provides some novel evidence and targets for combating the metabolic diseases.