Endocrine Abstracts

Background: In diabetes, exposure to frequent episodes of hypoglycaemia diminishes a persons awareness of hypoglycaemia, by poorly defined mechanisms. Evidence suggests that, at least in part, changes in cell behaviour within the ventromedial hypothalamus may contribute to this defect and that changes in AMP-activated protein kinase (AMPK), a key glucose-sensing enzyme are involved. Evidence suggests there are (mal)adaptations within neurons, however, little is known about cha...

Canrenone and mifepristone (RU486) are respectively mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) antagonists commonly used to block or displace steroid for clinical pharmacological or research purposes. The aim of this study was to develop and validate a sensitive, quantitative assay for the combined analysis of glucocorticoids (cortisol, cortisone, corticosterone, and 11-dehydrocorticosterone), mineralocorticoids (aldosterone), canrenoate, and mifepristone...

Background: Congenital hypothyroidism (CHT) may be viewed as a relatively easy condition to diagnose and treat. However, for the parents who are contacted with the neonatal screening results the news can be devastating. The quality of information provided at diagnosis is variable, and there are few support groups they can turn to. Many seek information online before meeting a paediatrician.Methods: The British Thyroid Foundation in conjunction with our r...

Activation of the hypothalamic–pituitary–adrenal (HPA) axis and altered tissue glucocorticoid action in obesity and metabolic syndrome has been attributed to altered peripheral cortisol metabolism. In human obesity, cortisol clearance is increased with up-regulation of A-ring reductases and down-regulation of cortisol-regenerating 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in liver, while in adipose tissue 11β-HSD1 is up-regulated. Rodent studi...

Canrenone is a mineralocorticoid receptor antagonist used as a diuretic agent to treat hypertension. It is the major active metabolite of spironolactone and may be quantified in clinical studies either to ensure compliance or to gain information about pharmacokinetic-pharmacodynamic interactions.The aim of this study was to develop and validate a sensitive, quantitative assay for the analysis of canrenone in plasma.HPLC mass spectr...

Introduction: There has been a joint transition clinic in our tertiary centre for over 10 years. We have recently undertaken a questionnaire based review of this service.Methodology: The questionnaire comprised two components: what the young adults understood about their condition and the medications they were currently taking using both a written response and a score of 0–10 for how confident they felt in this. They were also asked to complete a co...

Glucocorticoid (GC) excess adversely affects many aspects of skin homeostasis, characteristics of which are also seen during ageing (e.g. poor wound healing). The mechanisms underlying this remain unclear. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol, independently of circulating concentrations, and we have previously demonstrated increased 11β-HSD1 expression in human dermal fibroblasts (HDF) from aged donors. We have now e...

Background: 5α-Reductase (5αR) catalyses conversion of testosterone to its more potent metabolite dihydrotestosterone (DHT) and is inhibited when treating benign prostatic hyperplasia. 5αR has two isozymes; dual isozyme inhibition with dutasteride gives greater DHT suppression than finasteride, which inhibits only 5αR type 2.Aim: To develop a novel assay to simultaneously analyse testosterone, epitestosterone, DHT, androstenedione, du...

Background: Male hypogonadotrophic hypogonadism is an increasingly common cause of referral to endocrine clinics. Subnormal testosterone levels are frequently observed in obesity, type 2 diabetes mellitus and in the elderly. Endocrine Society guidelines suggest stratification of investigations based on the degree of androgen deficiency, with full pituitary function testing and MRI recommended only in those with serum testosterone levels less than 5.2 nmol/L. However the eviden...

Glucocorticoid excess is associated with increased anxiety and accelerated cognitive decline. Concentrations of glucocorticoids within tissues, including the brain, are influenced by local metabolism. 5α-Reductase 1 (5αR1), expressed in brain, converts corticosterone to its A-ring reduced metabolites, which have a different spectrum of activities. Here, we investigated if mice homozygous for disrupted 5αR1 alleles (5αR1-KO) experience heightened anxiety and...