Searchable abstracts of presentations at key conferences in endocrinology

ea0034p267 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

11β HSD1KO mice resist aged associated decline in markers of brown adipose tissue function

McCabe Emma , Doig Craig , Morgan Stuart , Larner Dean , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

The primary function of brown adipose tissue (BAT) is to use lipids to generate heat through uncoupling of oxidative phosphorylation in mitochondria. Glucocorticoids (GC) have a negative effect upon BAT through inhibition of uncoupling protein 1 (UCP1) expression. Similarly, it has been reported that BAT levels decline with age and have been linked to age related accumulation of body fat, leading to the idea that improving BAT function during ageing could have a beneficial rol...

ea0031oc1.3 | Young Endocrinologists prize session | SFEBES2013

11β-HSD1KO mice are protected from glucocorticoid dependent age-associated muscle atrophy

Hassan-Smith Zaki , Morgan Stuart , Bujalska Iwona , Abrahams Lianne , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoids (GCs) are prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including a decline in muscle mass and function which has similarities to age related sacropaenia. Within skeletal muscle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) amplifying local GC action. We hypothesise that 11β-HSD1 mediated intramyoce...

ea0031oc1.4 | Young Endocrinologists prize session | SFEBES2013

A serum microRNA profile potentially associated with glucocorticoid mediated insulin resistance

Gathercole Laura , Doig Craig , Hazlehurst Jonathan , Borrows Sarah , Stewart Paul , Lavery Gareth , Tomlinson Jeremy

Patients with glucocorticoid (GC) excess develop insulin resistance and central obesity. We have demonstrated that GCs have tissue-specific effects on insulin sensitivity in humans, causing resistance in skeletal muscle but sensitivity in subcutaneous adipose tissue. The molecular mechanisms that underpin these differences remain poorly understood. Over the last decade small non-coding RNAs (microRNAs–miRNAs) controlling protein expression have been identified, representi...

ea0031p332 | Steroids | SFEBES2013

Truncal fat distribution is associated with enhanced glucocorticoid excretion, increased 5α-reductase activity and higher insulin resistance independent of BMI in women with polycystic ovary syndrome

O'Reilly Michael , Hodson James , Crabtree Nicola , Hazlehurst Jon , Stewart Paul , Tomlinson Jeremy , Arlt Wiebke

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, hyperandrogenism and insulin resistance. Patterns of fat distribution in PCOS may be associated with androgen activation, glucocorticoid metabolism and insulin resistance. Here we analysed the relationship between fat distribution, steroid metabolism and insulin resistance in women with PCOS.We compared results from 100 PCOS patients (Rotterdam criteria) with 80 sex- and BMI-matched con...

ea0028oc4.2 | Steroid | SFEBES2012

Age-dependent increase in the expression/activity of 11β-HSD1 in key metabolic tissues may underpin the ageing phenotype notably sarcopenia

Morgan Stuart , Sherlock Mark , Lavery Gareth , Hassan-Smith Zaki , Abrahams Lianne , Stewart Paul

The pathophysiological effects of glucocorticoid (GC) excess (Cushing’s syndrome) are similar to the aging phenotype. As such, we hypothesise that age-related changed in body composition (central obesity, reduced bone density, reduced muscle mass and skin thinning), and resultant chronic disease (type 2 diabetes, osteoporosis, sarcopenia and heart disease) may be caused by increased GC exposure with age. However, circulating GC’s show little change with advancing age...

ea0028oc4.7 | Steroid | SFEBES2012

Glucocorticoids increase subcutaneous adipose tissue insulin sensitivity in vivo: a randomised double-blind, placebo controlled, cross over study

Hazlehurst Jonathan , Armstrong Matthew , Borrows Sarah , Gathercole Laura , Stewart Paul , Tomlinson Jeremy

Glucocorticoid (GC) excess, Cushing’s syndrome, is characterized by central obesity, proximal myopathy, insulin resistance and potentially type 2 diabetes mellitus. Current dogma dictates that GCs cause insulin resistance across all tissues. We have previously demonstrated that GCs cause insulin sensitization of human adipose tissue in vitro, whilst inducing insulin resistance in human skeletal muscle. No prior study has evaluated whether these observations transla...

ea0028p48 | Clinical practice/governance and case reports | SFEBES2012

A comparative quality assessment of evidence-based clinical guidelines in Endocrinology

Hazlehurst Jonathan , Armstrong Matthew , Sherlock Mark , O'Reilly Mick , Rowe Ian , Franklyn Jayne , Stewart Paul , Tomlinson Jeremy

Evidence-based clinical guidelines in Endocrinology attempt to improve and standardise patient care. There has been an expansion in guideline production although some of the heterogeneous methods used to assess the underlying evidence base may limit interpretation and implementation. Current and archived guidelines from The American Association of Clinical Endocrinologists (AACE), The Endocrine Society (ES), The American Thyroid Association, The British Thyroid Association and...

ea0028p201 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

24-hour urinary glucocorticoid metabolites are associated with hyperinsulinaemia independent of BMI in patients with the polycystic ovary syndrome

O'Reilly Michael , Hazlehurst John , Lebbe Marie , Stewart Paul , Tomlinson Jeremy , Arlt Wiebke

Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive and 5alpha-reductase activity, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with markers of insulin resistance in a large PCOS cohort. We compared results from 127 PCOS patients fulfilling Rotterdam diagnostic criteria with 100 B...

ea0028p302 | Steroids | SFEBES2012

Reversal of age-induced dermal atrophy in 11β-hydroxysteroid dehydrogenase type 1-null mice

Tiganescu Ana , Parish W , Walker Elizabeth , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoid (GC) excess, whether exogenously- or endogenously-derived, induces many adverse effects in skin including thinning, decreased cellularity and reduced collagen synthesis. Consequently, skin exhibits reduced dermal structural integrity, increased atrophy/fragility/bruising and impaired wound healing, effects that perfectly mimic skin ageing. Local GC levels are regulated in a tissue-specific manner by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes i...

ea0028p304 | Steroids | SFEBES2012

HSD11B1 promoter binding of the NF-κB p65 subunit in response to TNF-α suppresses 11β-HSD1 expression and activity in C2C12 muscle cells

Doig Craig , Bashir Jamila , Zielinska Agnieszka , Cooper Mark , Stewart Paul , Lavery Gareth

A counter-regulatory rise in GC levels is important to the inflammatory response, that when impaired is associated with high mortality in inflammatory states. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerate’s intracellular glucocorticoids (GC), amplifying their actions, and has been postulated to play a role in the development of inflammation-associated arthritis, obesity and myopathy. Pro-inflammatory cytokines (e.g. TNF-α) increase expressio...