Endocrine Abstracts

Hypertension is a common risk factor for cardiovascular disease and up to 15% of hypertensive patients are now known to have primary aldosteronism (PA), where the adrenal glands secrete inappropriately high levels of the steroid hormone aldosterone. Of these cases, almost half are due to the presence of unilateral aldosterone-producing adenoma (APA). Aldosterone is synthesised in the zona glomerulosa of the adrenal cortex, with the final stages of production catalysed by aldos...

Glucocorticoids (GC) are commonly prescribed, but their use is associated with significant adverse metabolic and bone effects. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active GC within tissues, tightly controlling the availability of GC to bind and activate the GC receptor; Our preclinical data have shown that 11β-HSD1 knock out mice resist the adverse effects of exogenous GC excess. We have now conducted a randomized, double-blind, placebo...

Within the synovium of patients with rheumatoid arthritis (RA), synovial fibroblasts generate active corticosteroids through expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In vitro, this enzyme is strongly up-regulated by pro-inflammatory cytokines such as tumour necrosis factor α (TNFα) and IL1β. In this study, we determined the relationship between inflammation and global 11β-HSD1 activity in vivo, in a clini...

The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme is a tissue specific regulator of glucocorticoid action that is linked to the development of osteoporosis, inflammatory arthritis and myopathy. Systemic inhibition of 11β-HSD1 enzyme activity has been proposed as a therapeutic option in these conditions. However, 11β-HSD1 activity has also been reported to be important in regulation of the immune response and the HPA axis. We have previously demo...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The role of glucocorticoids (GC) in its pathogenesis, is highlighted in patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although circulating cortisol levels are normal in patients with NAFLD, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11&#94...

Acromegaly is associated with increased morbidity and mortality. Surgery, radiotherapy (RT) and medical therapy are the treatment options to decrease GH and IGF-I concentrations to levels associated with cure or normalisation of mortality. We examined the response to dopamine agonists (DA) and somatostatin analogues (SSA) in 276 patients with acromegaly who received medical therapy during follow up (198 DA, 143 SSA). One hundred and seventy two had surgery and 73 RT prior to m...

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

Acromegaly is associated with increased morbidity and mortality. There are several treatment options for acromegaly including surgery, radiotherapy and medical therapy. The aims of treatment in patients with acromegaly is to achieve GH and IGF-I concentrations associated with cure or normalisation of mortality.We examined predictive factors of response to treatment with dopamine agonists (DA) and somatostatin analogues (SSA) in a cohort of 501 patients w...

Acromegaly is associated with increased morbidity and premature mortality which has been demonstrated in a number of retrospective studies reporting a standardised mortality ratio (SMR) between 1.3 and 3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or surgery and/or radiotherapy. Hypopituitarism is also associated with an increased SMR (1.2–2.17).Using the West Midlands Acromegaly database (n<...

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Increased 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impa...