Endocrine Abstracts

Glucocorticoids have potent effects on almost every tissue in the body and this is exemplified in patients with Cushing’s disease. Whilst Cushing’s disease is rare, glucocorticoids are commonly prescribed for their anti-inflammatory actions, but their use is associated with a series of undesirable adverse effects, including obesity, insulin resistance, hypertension, myopathy and osteoporosis. Within tissues, glucocorticoids (both endogenous and exogenous) are metabol...

Within tissues, glucocorticoids (both endogenous and exogenous) are metabolised by a series of enzymes that have the ability to tightly control local hormone availability and thus regulate binding to, and activation of, the glucocorticoid receptor. The 11β-hydroxysteroid dehydrogenases (type 1 [11β-HSD1] and type 2 11β-HSD2]) interconvert active (cortisol, prednisolone and corticosterone) and inactive glucocorticoids (cortisone, prednisone and 11-dehydrocorticos...

Steroid hormones have potent metabolic effects. Glucocorticoid excess is characterized by central adiposity, insulin resistance, type 2 diabetes and increased cardiovascular risk. Whilst endogenous glucocorticoid excess is rare, local tissue-specific availability of glucocorticoid is controlled by a series of enzymes that are, at a pre-receptor level, able to regulate cortisol’s ability to bind and activate the glucocorticoid receptor. 11β-hydroxysteroid dehydrogenas...

Critical illness is associated with significant morbidity and mortality. The changes in the hypothalamo-pituitary-adrenal (HPA) axis that occur during critical illness are complex and whilst early studies had suggested improved outcome in patients with septic shock treated with parenteral glucocorticoids, this was not endorsed in subsequent studies and it remains a highly controversial area.In patients with underlying pituitary or adrenal disease where c...

Two to three percent of the UK population are prescribed glucocorticoid (GC) therapy and their adverse effects are associated with significant morbidity and mortality. Suppression of the hypothalamo-pituitary–adrenal (HPA) axis with the potential risk of adrenal crisis is a recognised complication of therapy. There are significant clinical challenges, not only recognition and diagnosis of the condition, but also in terms of management. There is no doubt that the prevalenc...

Current dogma suggests that glucocorticoids (GCs) cause insulin resistance in all tissues. Whilst it is clear that they cause global, whole body insulin resistance, we have challenged the concept that the actions of GCs are the same in all tissues. Using a variety of human cell-based models, we have shown that in contrast to their actions in skeletal muscle and liver, GCs cause insulin sensitization in human adipose tissue, enhancing insulin-stimulated PKB/akt phosphorylation,...

The global epidemic of obesity and type 2 diabetes has hastened the need to identify novel and efficacious therapies. Based upon parallels with Cushing’s syndrome, tissue specific cortisol excess, independent of circulating levels, has been suggested to have a crucial pathological role and may represent a potential treatment target. In key metabolic target tissues (liver, adipose and muscle), the endoluminal enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-H...

The global epidemic of obesity and its associated complications has hastened the need with which we must understand both the patho-physiological process that contribute to its development, and also the urgency with which we need therapeutic solutions that offer clinically meaningful and sustained weight loss. There is clear evidence as to the beneficial impact of exercise upon health, in particular cardiovascular health, in normal weight and obese individuals as well as those ...

Polycystic ovary syndrome (PCOS) is one of the most prevalent conditions facing the clinical endocrinologist, affecting 5–10% of all women. The condition is characterized in part, by clinical and / or biochemical androgen excess. Despite its prevalence, the molecular mechanisms that contribute to its pathogenesis remain relatively poorly understood. Whilst androgen excess forms part of the diagnostic criteria, the source of the androgen excess is unclear, and ovarian, adr...

The global epidemic of obesity has heightened the need to understand the mechanisms that contribute to its pathogenesis and also to design and trial novel treatments. Patients with glucocorticoid (GC) excess, ‘Cushing’s syndrome’ share many phenotypic similarities to patients with simple obesity. GC availability to bind and activate the glucocorticoid receptor (GR) is controlled by the type 1 isoform of 11β-hydroxysteroid dehydrogenase (11β-HSD1) that ...