Searchable abstracts of presentations at key conferences in endocrinology

ea0002p53 | Growth and development | SFE2001

Insulin-like growth factor acts as a Nitric-oxide-dependant vasodilator in normotensive but not hypertensive rat aortas

McCallum R , Hamilton C , Graham D , Jardine E , Connell J , Dominiczak A

Insulin-like growth factor (IGF-1) has been postulated to function as a vasodilator via a nitric oxide (NO) pathway. IGF-1/growth hormone deficiency in humans is associated with endothelial dysfunction and increased cardiovascular mortality.We compared the effects of IGF-1 on vascular function in control Wistar-Kyoto (WKY) (n=6) and stroke-prone spontaneously hypertensive rats characterised by endothelial dysfunction (SHRSP) (n=7)....

ea0034oc3.5 | Steroids | SFEBES2014

Linking GWAS to gene function: CYP17A1 in hypertension

Diver Louise , MacKenzie Scott , McManus Frances , Freel Marie , Friel Elaine , Fraser Robert , Hanley Neil , Connell John , Davies Eleanor

Recent genome-wide association studies (GWAS) implicate the CYP17A1 locus in human blood pressure regulation. This gene is important in steroidogenesis, regulating both glucocorticoid and androgen synthesis through catalysis of 17α-hydroxylation and 17,20 lyase reactions. We hypothesised that functional CYP17A1 polymorphisms linked to those identified by GWAS influence blood pressure levels. We therefore screened the entire CYP17A1 locus by dire...

ea0028p303 | Steroids | SFEBES2012

Demonstration of blood pressure-independent diffuse cardiac fibrosis in Primary Aldosteronism- a cardiac MRI study

Freel Ellen , Mark Patrick , Weir Robin , McQuarrie Emily , Allan Karen , Dargie Henry , Jardine Alan , Davies Eleanor , Connell John

Background: Primary Aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Animal and in vitro studies have demonstrated that exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy and this may, partly, be mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in humans using contrast-enhanced cardiac MRI as well a...

ea0025p291 | Steroids | SFEBES2011

Urinary tetrahydrodeoxycorticosterone excretion is a significant independent predictor of LV mass in patients with chronic kidney disease

McQuarrie Emily , Mark Patrick , Patel Rajan , Fraser Robert , Davies Eleanor , Steedman Tracey , Connell John , Freel E Marie

Aim: Increasing left ventricular mass index (LVMI) is associated with a poor prognosis in patients with chronic kidney disease (CKD). Blockade of the mineralocorticoid receptor (MR) in CKD leads to improvement in proteinuria and LV mass. However, the MR can be activated by aldosterone, cortisol and deoxycorticosterone (DOC) and their relative contribution to adverse events in CKD is unclear. We aimed to assess the correlation between mineralocorticoid excretion and LVMI in pat...

ea0015p95 | Clinical practice/governance and case reports | SFEBES2008

Impact of NICE guidelines for adult growth hormone replacement on practice in Scotland

Philip Sam , Howat Isabel , Carson Maggie , Booth Anne , Patterson Catherine , Schofield Christopher , Patrick Alan , Leese Graham , Bevan John , Connell John

Aim: To assess whether adults in Scotland currently receiving growth hormone (GH) meet the NICE criteria for starting and continuing GH replacement.Methods: We surveyed all endocrinologists in Scotland and identified the main centres using GH replacement. A cross-sectional case note review was carried out of all patients commenced on GH.Results: About 208 patients (51% women; 24% professionals, 90% Caucasian) were identified, 69 of...

ea0015p325 | Steroids | SFEBES2008

Heritability of plasma aldosterone levels and genetic variation association with the aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes

Alvarez-Madrazo Samantha , Padmanabhan Sandosh , Wallace Michael , Campbell Morvern , Friel Elaine , Keavney Bernard , Davies Eleanor , Connell John

Aldosterone plays a key role regulating electrolyte homeostasis and blood pressure. An elevated aldosterone to renin ratio is present in 15% of hypertensive patients but the causes of aldosterone excess are not fully understood. There is evidence of interaction between the polymorphisms in the aldosterone synthase gene (CYP11B2) and aldosterone levels in plasma and urine. However, the most consistent associations between variation at this locus and altered steroid synth...

ea0013p93 | Clinical practice/governance and case reports | SFEBES2007

NICE Guidelines for Adult Growth Hormone replacement: an audit of impact on practice in Scotland

Philip S , Carson M , Howat I , Patterson C , Schofield C , Booth A , Patrick AW , Leese GW , Bevan JS , Connell JMC

Background: National Institute for Clinical Excellence (NICE) guidelines for the use of Growth Hormone (GH) replacement in adults with GH deficiency (GHD) were published in 2003, and subsequently ratified for use in Scotland.Aim: To identify all adults in Scotland currently receiving GH and to assess whether they meet the NICE criteria for starting and continuing GH replacement.Methods: All endocrinologists in Scotland were surveye...

ea0011p305 | Diabetes, metabolism and cardiovascular | ECE2006

A gene gene interaction of single nucleotide polymorphisms within two oxidative stress genes affects arterial compliance in patients with coronary artery disease

Drummond RS , Koh-Tan HHC , Brain NJR , McClure JD , Cherry LM , Kirk AJB , Sattar N , Connell JMC , Dominiczak AF

We hypothesised that SNPs within oxidative stress genes influence vascular compliance in patients with coronary artery disease.A SNP within the gene encoding the eNOS (NOS3) which encodes a Glu298→Asp amino acid substitution has been associated with cardiovascular disorders in which NO bioactivity is impaired. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system, a major source of vascular SO, is CYB...

ea0009oc31 | Oral Communication 4: Steroids | BES2005

Functional effects of mutations in the 11beta-hydroxylase (CYP11B1) gene

Barr M , Wilkinson D , Holloway C , Miller S , MacKenzie S , Kazi S , Fraser R , Connell J , Davies E

Up to 15% of unselected patients with hypertension have evidence of inappropriate aldosterone production, identified by a raised ratio of plasma aldosterone to renin (ARR), suggesting that altered regulation of aldosterone synthesis is a key intermediate phenotype in essential hypertension. We previously described an association between the -344C/T 5'UTR polymorphism in the CYP11B2 (aldosterone synthase) gene and hypertension with raised ARR; the same genetic variation associa...

ea0008oc22 | Young Endocrinologist Session | SFE2004

Effect of Variation at the Aldosterone Synthase Locus (CYP11B2) on Adrenal 11-beta hydroxylation: Pilot Data from the MRC BRIGHT Study

Freel M , McKenzie S , Friel E , Ingram M , Davies E , Fraser R , Dominiczak A , Caulfield M , Connell J

Aldosterone is an important cardiovascular hormone. Around 15 % of hypertensives have alteration in aldosterone regulation, defined by a raised ratio of aldosterone to renin (ARR). Studies of CYP11B2, the aldosterone synthase gene, focus on a single nucleotide polymorphism in the 5'promotor region (-344 C/T). We have shown that the T allele is associated with increased urinary excretion and plasma levels of aldosterone and is more common amongst hypertensives with a raised ARR...