Endocrine Abstracts

Glucocorticoids (GC) have potent actions upon human adipose tissue, promoting adipocyte differentiation, inhibiting preadipocyte proliferation and inducing lipolysis to generate free fatty acids (FFA) and glycerol through a putative action upon hormone sensitive lipase (HSL). FFA have been strongly implicated in the pathogenesis of insulin resistance, yet the molecular mechanisms that cause GC induced lipolysis are not clear. Recently, several novel lipases have been identifie...

Glucocorticoid (GC) excess is characterized by central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. Whilst it is accepted that GCs cause insulin resistance, both insulin and GCs act synergistically to promote adipocyte differentiation. We have previously shown that GCs cause tissue specific changes in insulin sensitivity, enhancing insulin signalling in human adipose tissue in contrast to muscle.TRB3, a mammalian homolog of <i...

Background: Adrenal incidentalomas are common and require investigation to exclude malignancy and evidence of hormone overproduction. Clinical guidelines recommend overnight dexamethasone suppression tests (ONDST) to assess for cortisol hypersecretion with cortisol levels of 50-138 nmol/l termed “mild autonomous cortisol secretion” (MACS). MACS may be associated with both cardiovascular and metabolic morbidity. We assessed cardiovascular risk in patients with MACS us...

Volume 82, Issue 1, January 2015, Pages 2–11. DOI: 10.1111/cen.12603...

Glucocorticoids (GC) drive multiple adverse effects in skin e.g. epidermal thinning, dermal atrophy and impaired wound healing (WH). Our previous findings indicate increased expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in primary human dermal fibroblasts (HDF), full-thickness skin from older donors and during the inflammatory phase of mouse skin WH. We also reported protection from age-induced dermal atrophy and improved W...

Glucocorticoids (GC) are critical to stress adaptation but in excess (Cushing’s syndrome) drive metabolic dysfunction. 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1) amplifies intracellular GC signaling with 11β-HSD1KO mice protected from the side-effects of GC excess. Brown adipose tissue (BAT) function is impaired by GC’s, which repress UCP1 and beta-adrenergic stimulated thermogenesis. Identifying mechanisms regulating BAT function is important a...

Introduction: Patients with adrenal insufficiency (AI) (primary (PAI), secondary to pituitary disease (PIT) and congenital adrenal hyperplasia (CAH)) have reduced life expectancy with reported standardized mortality ratios of ~2:1 but given the rarity of AI, the underlying explanation remains largely unknown.Objective: To evaluate patient characteristics, prevalence of concomitant conditions and hospitalization incidence in patients with AI compared to a...

Introduction: The clinical outcome of patients with adrenal insufficiency (AI) has been shown to be less favorable than previously thought. Clinical studies have shown increased mortality, reduced cardiovascular and skeletal health and compromised quality of life, but the impact of this upon healthcare burden is unknown. This research utilised real-world evidence to compare comorbidities, healthcare utilization and expenditures in patients with AI.Method...

Introduction: There is growing evidence that 11β-HSD1 expression/activity increases with age in key target tissues including adipose tissue, bone, and skin, implicating local amplification of glucocorticoids in the pathophysiology of related disease. We have previously shown that 11β-HSD1KO mice are protected from both the adverse metabolic effects of excess glucocorticoids and age-associated muscle weakness. We investigated changes in global activity and skeletal mu...

2–3% of the UK population are prescribed glucocorticoid (GC) therapy and their adverse effects contribute to a significant health burden. Suppression of endogenous GC secretion is a recognized complication of therapy, but the magnitude of the problem, together with its clinical consequences have not been determined. We conducted a retrospective study across all specialties in a large secondary–tertiary care center identifying 2782 patients who underwent 3666 250 &#95...