Endocrine Abstracts

Context: Androgen excess, obesity and hyperinsulinaemia are the cardinal features of polycystic ovarian syndrome (PCOS). While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remains largely undefined. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. Here, we evaluated the relationship between visceral fat and androgen excess in w...

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...

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...

Background: Delivery of clinical trials to time and target is critical for studies to be financially viable and relevant. Feasibility studies are informative. However, protocol acceptability and recruitment rates can only be accurately ascertained once a study is open.The SCIPI study (SubCutaneous Insulin: Pumps or Injections?), randomises patients to treatment with multiple daily injections (MDI) or pumps at diagnosis of type I diabetes (TID). A consent...

Introduction: Generously supported by IPSEN)-->Measurement of salivary cortisol is a simple, convenient, accurate and reproducible technique with potential value during the diagnosis/management of hypercortisolism. Current analysis evaluates changes in late-night salivary cortisol (LNSC) during pasireotide treatment in patients with Cushing’s disease (CD).Methods: A 12 m, Phase III study enrolled 162 adult...

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 ...

Introduction: Rapid and sustained decreases in UFC and significant improvements in signs and symptoms were seen in a large, randomized, 12-month phase III study of pasireotide in Cushing’s disease. The safety profile of pasireotide was found to be similar to that of other somatostatin analogues, with the exception of hyperglycemia-related AEs (reported in 72.8% of patients). This abstract reports safety data from a 12-month extension to this phase III trial.<p class="...

Introduction: The large, randomized, phase III study of pasireotide in Cushing’s disease found that pasireotide treatment resulted in rapid and sustained decreases in UFC levels and in significant improvements in signs and symptoms over 12 months of treatment. A 12-month extension of this trial has recently completed, and the results are reported here.Methods: Patients with persistent/recurrent or de novo (if not surgical candidates) Cushing&...

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...

Familial glucocorticoid deficiency (FGD;OMIM 202200) results from the inability of the adrenal cortex to produce cortisol in response to ACTH stimulation. Half of all cases are caused by mutations in MC2R, MRAP or STAR. SNP array genotyping of FGD patients of unknown aetiology mapped a disease locus to chromosome 5p13-q12. Targeted exome sequencing of 5p13-q12 in one patient identified a homozygous mutation, p.Ala533Val, in nicotinamide nucleotide transhyd...