Searchable abstracts of presentations at key conferences in endocrinology

ea0094op3.2 | Reproductive Endocrinology | SFEBES2023

Abnormal uterine bleeding (AUB) and COVID-19: investigating associations and potential mechanisms

Watters Marianne , Alvergne Alexandra , Walker Catherine , Robb Cara , Critchley Hilary , Kountourides Gabriella , Austin Argentieri , Sharp Gemma , Olszewska Zuzanna , Maybin Jacqueline

Women with COVID-19 and Long COVID (symptoms >4 weeks) have reported AUB. We investigated (i) the association between COVID-19/Long COVID and AUB and (ii) ovarian sex hormones across the menstrual cycle in women with Long COVID. Two studies were completed with ethical approvals and consent. Firstly, a retrospective online survey ‘The Covid-19 Pandemic and Women’s Reproductive Health’ was conducted March-May 2021 with UK participants >18 years old (n<...

ea0094p171 | Adrenal and Cardiovascular | SFEBES2023

A clinical case demonstrating the challenges in diagnosing and managing Paraneoplastic Cushing’s Syndrome

Iqbal Zohaib , Ho Jan , Walker Leanne , White Ann , Monaghan Philip , Thirkettle Sally , Gulamhusein Aziz , Keevil Brian , Mansoor Wasat , Adam Safwaan

We present a case of a 62-year-old lady with a grade 3 well-differentiated metastatic gastric-neuroendocrine tumour complicated by symptoms of CS (weight-gain, bruising, proximal weakness) which developed over 4 weeks. She had progressive disease after exhausting all conventional anti-neoplastic therapeutic options. Screening tests revealed raised 24-h urinary free cortisol (3460 nmol/24h[<165]), post-overnight dexamethasone suppression serum cortisol (serF) 1200 nmol/l(&#...

ea0098b21 | Basic Science | NANETS2023

Transcriptomic profiling of the BCL-2 pathway in Neuroendocrine Neoplasms (NENs)

Sukrithan Vineeth , Ahmed Uzair , Krause Harris , Gandhi Nishant , Walker Phillip , Lou Emil , Soares Heloisa , Vanderwalde Ari , Konda Bhavana

Background: BCL-2 is an anti-apoptotic protein associated with resistance to tumor cell death and is a histopathologic marker of neuroendocrine differentiation. We characterized the transcriptomic profile of BCL2 expression in NENs and its association with site, immune infiltration, and overall survival (OS).Methods: Next-generation sequencing of both DNA (592-gene panel or whole exome) and RNA (whole transcriptome) was performed on NENs of pancreatic (P...

ea0081p283 | Adrenal and Cardiovascular Endocrinology | ECE2022

A single dose of Neutrophil Elastase inhibitor Elafin does not alter CBG cleavage during post-surgical stress in humans in vivo

Boyle Luke D , Nixon Mark , Underhill Caroline , Hill Lesley A , Lewis John G , Hammond Geoffrey L , Wiedow Oliver , Henriksen Peter A , Stimson Roland H , Walker Brian R

Introduction: Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and modulates free cortisol levels. Observations in vitro show that CBG is cleaved by neutrophil elastase (NE), a mechanism proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. However, detection of cleaved CBG in vivo in human plasma is controversial, and any influence of NE on CBG cleavage has not been tested in vivo...

ea0050p005 | Adrenal and Steroids | SFEBES2017

20β-Dihydrocortisol; a weak endogenous agonist of the glucocorticoid receptor but a potent agonist of the mineralocorticoid receptor

Morgan Ruth , Beck Katharina , Nixon Mark , Homer Natalie , Melchers Diana , Houtman Rene , Meijer Onno , Hadoke Patrick , Odermatt Alex , Keen John , Walker Brian

Cortisol conversion to 20β-dihydrocortisol (20β-DHF) has been reported in many tissues and cells, including skin, muscle, thrombocytes and fibroblasts, although the enzyme responsible is poorly characterised. We have attributed 20β-DHF generation to carbonyl reductase 1 and shown increased activity of this pathway in adipose tissue in obesity in humans, horses and mice. This study addressed the hypothesis that 20β-DHF activates gl...

ea0050p005 | Adrenal and Steroids | SFEBES2017

20β-Dihydrocortisol; a weak endogenous agonist of the glucocorticoid receptor but a potent agonist of the mineralocorticoid receptor

Morgan Ruth , Beck Katharina , Nixon Mark , Homer Natalie , Melchers Diana , Houtman Rene , Meijer Onno , Hadoke Patrick , Odermatt Alex , Keen John , Walker Brian

Cortisol conversion to 20β-dihydrocortisol (20β-DHF) has been reported in many tissues and cells, including skin, muscle, thrombocytes and fibroblasts, although the enzyme responsible is poorly characterised. We have attributed 20β-DHF generation to carbonyl reductase 1 and shown increased activity of this pathway in adipose tissue in obesity in humans, horses and mice. This study addressed the hypothesis that 20β-DHF activates gl...

ea0086oc4.3 | Adrenal and Cardiovascular | SFEBES2022

Plasma steroid concentrations reflect disease severity during acute illness but not recovery after hospitalisation with COVID-19

Devine Kerri , Walker Brian R , Homer Natalie ZM , Openshaw Peter JM , Kenneth Baillie J. , Andrew Ruth , Wain Louise V , Semple Malcolm G , Reynolds Rebecca M

Background: Endocrine systems are known to be disrupted in acute illness, and we previously demonstrated that plasma steroid concentrations correlated with severity in patients hospitalised with COVID-19. Given their similarity to some clinical hormone deficiencies, we hypothesised that ‘long-COVID’ symptoms may be related to ongoing endocrine dysfunction.Methods: Plasma steroids, precursors and metabolites were quantified by LCMS/MS in multi-c...

ea0049ep802 | Nuclear receptors and Signal transduction | ECE2017

5α-THB as a novel anti-inflammatory drug: The roles of the glucocorticoid and mineralocorticoid receptors

Abernethie Amber , Gastaldello A , Morgan RA , Mitchell C , McInnes KJ , Beck K , Odermatt A , Houtman R , Melchars D , Meijer OC , Hadoke PWF , Livingstone DEW , Walker BR , Andrew R

Glucocorticoids (GC) are potent anti-inflammatory compounds, acting mainly through the glucocorticoid receptor (GR). GC therapy, however, has debilitating side-effects, necessitating safer new alternative therapies. The natural GC metabolite 5α-Tetrahydrocorticosterone (5αTHB) is anti-inflammatory in vivo in mice, but with fewer side-effects. Its mechanism of action is unknown, and here we test signalling via GR and the mineralocorticoid receptor (MR). 5&#94...

ea0035oc5.2 | Adrenal &amp; Thyroid | ECE2014

Relationship between final height and cardiometabolic risk and quality of life in adults with congenital adrenal hyperplasia: United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)

Han Thang S , Conway Gerard S , Krone Nils , Aled Rees D , Stimson Roland H , Arlt Wiebke , Walker Brian R , Ross Richard J

Background: Treatment of CAH in childhood focuses on growth and development; however the impact of final height (FH) on adult health is not known. We examined the relationship between FH, adiposity, cardiometabolic risk and quality of life (QoL) in a cohort of adult patients.Methods: Cross-sectional analysis of 199 adults with CAH. FH, waist circumference (WC) and QoL were expressed as z-scores adjusted for mid-parental target height (FHTH<...

ea0034p249 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Derivatisation of estrogens enhances specificity and sensitivity of analysis by liquid chromatography tandem mass spectrometry

Faqehi Abdullah M M , Cobice Diego F , Naredo Gregorio , Mak Tracy C S , Walker Brian R , Homer Natalie Z M , Andrew Ruth

Physiological circulating concentrations of estrogens are very low in men and postmenopausal women (<50 pg/ml), which presenting analytical challenges. Immunoassays can detect as low as 30 pg/ml, but cross-reactivity is a concern. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) offers greater specificity than immunoassays, but ionisation of estrogens is inefficient. Derivatisation, which introduces charged moieties, may enhance ionisation. Dansylated de...