Endocrine Abstracts

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

Severe growth hormone (GH) deficiency in adults is associated with adverse changes in quality of life (QoL), body composition and cardiovascular risk profile. NICE guidance restricts GH replacement in the UK to those with impaired QoL, defined by a score of >11 in the QoL-AGHDA questionnaire.Aims: To assess whether the NICE guidance differentiates other clinical or biochemical features in GH deficient adults.Patients and...

GH deficiency (GHD) in adults shares several clinical features with syndromes of glucocorticoid excess. Many patients with GHD also receive glucocorticoid therapy. GH inhibits the generation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), but the confounding effect of ACTH deficiency/ cortisol replacement therapy has not been evaluated.Aims: To assess corticosteroid exposure and metabolism and body composition in...

Background: The CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) genes are found in close proximity on human chromosome 8 and are highly polymorphic, enabling the definition of two common haplotypes. Haplotype1 includes the -344T and the Intron2 conversion polymorphisms in CYP11B2 and also the -1889T, -1859G polymorphisms in the regulatory region of CYP11B1. We and others have shown that these associate with increased aldosterone pr...

GH/IGF1 stimulate muscle function whereas excess glucocorticoids induce myopathy. Myocytes express 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme which converts inactive cortisone to active cortisol. GH/IGF-I inhibit 11β-HSD1 expression in some tissues and thus reduce cellular glucocorticoid exposure. This suggests that anabolic actions of GH/IGF1 could be mediated indirectly through effects on 11β-HSD1. The regulation of 11β-HSD1 has be...

The corticosteroids aldosterone and cortisol are implicated in the aetiology of hypertension. The CYP11B1 and CYP11B2 genes encode 11β-hydroxlylase and aldosterone synthase; polymorphisms across the CYP11B1/B2 locus are associated with increased aldosterone production, inefficient 11β-hydroxlation and hypertension. While polymorphisms located in the promoter region of both genes may alter transcription factor binding, other variants located in th...

Interferon therapy for chronic hepatitis C infection has been associated with thyroid abnormalities. We sought to characterise the incidence of this in a cohort of treated hepatitis C patients receiving weekly pegylated interferon therapy in a tertiary Hepatology unit. Patients were scheduled to receive 24 or 48 weeks treatment with monthly thyroid function tests (TFTs). Data was collected from electronic treatment records of 154 consecutive patients and analysed by a single i...

The intraperitoneal environment of the ovarian surface epithelium (OSE) has an oxygen (O2) tension of 5–12%. This could impact cellular events leading to ovulation. Furthermore, ovarian cancers arising from the OSE (∼80–90% of ovarian malignancies) are likely to experience increased hypoxia due to the relatively poor vascularisation of solid tumours.Using 1%, 5% or 20% O2, we measured the expression of HSD11B1, COX-2...

The eye is an organ vulnerable to a variety of external and internal stimuli that can abolish its vital function to allow accurate vision of images for survival. Inflammation is the key mediator of immune protection but its consequence leads to the disruption of the visual axis integrity. Due to this precise reason, through adaptation and evolution, the eye has developed mechanisms of immune tolerance and privilege. Glucocorticoids have potent immunosuppressive and anti-inflam...

Hexose-6-phosphate dehydrogenase (H6PD) is a sarcoplasmic reticulum (SR) resident enzyme that metabolizes glucose-6-phosphate and generates NADPH that drives the activation of glucocorticoids by 11β-hydroxysteorid dehydrogenase type 1. H6PD KO mice exhibit improved skeletal muscle insulin sensitivity increased glucose uptake and glycogen storage. However, H6PD KO mice also develop a myopathy with switching from Type II to Type I fibers. Affected muscles have apparently no...