Endocrine Abstracts

Background: Excess glucocorticoid (GC) exposure is associated with an adverse body composition and metabolic profile characterised by increasing fat mass, muscle atrophy, insulin resistance, fatty liver, and dyslipidaemia culminating in increased cardiovascular risk. GCs are widely prescribed with increasing age where their effects can have deleterious effects.Objectives: To investigate the impact of GC exposure on subcutaneous adipose lipid metabolism a...

Background: The short Synacthen test (SST) is the most widely used dynamic assessment of adrenal reserve. In some situations, the SST may be difficult to perform. Random basal cortisol levels could provide an alternative screening assessment to rationalize which patients need dynamic testing. This is highly clinically relevant, given the large numbers of patients taking prescribed glucocorticoids who are at risk of iatrogenic adrenal suppression.Methods:...

Glucocorticoids are widely prescribed for their anti-inflammatory properties, but have a significant adverse effect profile, leading to a Cushingoid phenotype. In the present study, we test the hypothesis that reactivation of glucocorticoids, in peripheral tissues by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), is a major determinant of exogenous Cushing’s syndrome.WT, global 11β-HSD1 knockout (GKO), liver-specific 11β-HSD...

Dysregulation of the enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistant states, however longitudinal changes in glucocorticoid metabolism over time have not been investigated. This study was designed to evaluate the role of pre-receptor glucocorticoid metabolism in the development of insulin resistance and obesity. 24 h urinary glucocorticoid and mineralocorticoid metabolites were measured by gas chroma...

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess. Hyperandrogenism may correlate with metabolic risk but PCOS consensus criteria currently define androgen excess on the basis of serum testosterone only. Here we studied the utility of the androgen precursor serum androstenedione in conjunction with serum testosterone as a predictor of metabolic dysfunction in PCOS.86 PCOS patients fulfilling Rott...

Muscle wasting remains a significant complication in patients with inflammatory disease where it contributes to disability, risk of falls and early mortality. Interestingly, muscle wasting in patients with glucocorticoid excess mirrors that observed in patients with inflammatory disease. We have previously reported that the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is potently up-regulated within mesenchymal derived cell popu...

Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accu...

The causative link between circulating glucocorticoid excess and osteoporosis is established. Although circulating cortisol levels do not change significantly with age, local tissue metabolism may be implicated in age-related bone loss. The enzyme11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) increases local cortisol production, is expressed in human osteoblasts and its activity increases with age leading to a decrease in bone formation. We hypothesised that sele...

In the pathogenesis of obesity, dysregulated tissue cortisol metabolism (controlled by 11β-HSD1), is postulated to be involved. Fifteen patients (seven mens, mean BMI 50.8±7 kg/m2) awaiting Roux En Y gastric Bypass (RYGB) surgery underwent assessment of 11β-HSD1 activity using cortisol generation profile. Corticosteroids in serum and subcutaneous adipose tissue microdialysis fluid and urinary corticosteroid metabolites were analysed by liquid and gas ...

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...