Endocrine Abstracts

Background: Glucocorticoids are frequently used to treat childhood inflammatory disorders, and may cause increased fracture predisposition with reduced bone mineral density (BMD), particularly from trabecular bone loss. The contribution of the underlying inflammatory disease processes to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) is a useful model to investigate the effects of steroids on bone, as recurrent courses are often required, but systemic i...

Glucocorticoids (GCs) are prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including a decline in muscle mass and function which has similarities to age related sacropaenia. Within skeletal muscle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) amplifying local GC action. We hypothesise that 11β-HSD1 mediated intramyoce...

Introduction: Obesity is characterized by an expanded and chronically inflamed adipose tissue (AT). The galectin (Gal) family of proteins exerts a variety of activities, including regulation of inflammation and adipogenesis.Methods: We used RT-PCR, ELISA and flow cytometry to evaluate regulation of expression and production of 4 members of the Gal family – Gal1, Gal3, Gal9 and Gal12 – in visceral (VAT) and subcutaneous (SAT) adipose tissue of m...

Aims: To ascertain the incidence of hypo- and hyper-natraemia in patients admitted to a tertiary neurosurgical centre with confirmed spontaneous aneurysmal subarachnoid haemorrhage (SAH), and to determine their impact on length of hospital stay and mortality.Methods: Retrospective case note review of patients admitted between January 2008 and April 2011.Results: 402 patients with SAH were identified [mean (±sd</sma...

Glucocorticoid (GC) excess, whether exogenously- or endogenously-derived, induces many adverse effects in skin including thinning, decreased cellularity and reduced collagen synthesis. Consequently, skin exhibits reduced dermal structural integrity, increased atrophy/fragility/bruising and impaired wound healing, effects that perfectly mimic skin ageing. Local GC levels are regulated in a tissue-specific manner by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes i...

A counter-regulatory rise in GC levels is important to the inflammatory response, that when impaired is associated with high mortality in inflammatory states. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerate’s intracellular glucocorticoids (GC), amplifying their actions, and has been postulated to play a role in the development of inflammation-associated arthritis, obesity and myopathy. Pro-inflammatory cytokines (e.g. TNF-α) increase expressio...

Rheumatoid arthritis (RA) is associated with a loss of lean mass and a corresponding increase in fat mass. How fat accumulation in RA is linked to synovial inflammation is unknown. Wnts comprise a family of secreted glycoproteins that are crucial in regulating adipocyte proliferation, apoptosis and differentiation. Recently we demonstrated that endogenously generated glucocorticoids (GCs) alter the pattern of wnt secretion by synovial fibroblasts (SFs), favouring production of...

Osteosarcoma (OS) is an aggressive malignant tumour of osteoblasts occurring predominantly in children and young adults. Despite chemotherapy relapse is common and mortality remains ~50%. Non-transformed osteoblasts are highly sensitive to glucocorticoids which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme powerfully inactivates cortis...

Glycogen storage diseases (GSD) are autosomal recessive inborn errors of carbohydrate metabolism. With current dietary therapy, life expectancy in patients with GSD has improved considerably and almost all children reach adulthood. Notwithstanding intensive therapy, patients with GSD have an increased risk of osteoporosis. We followed 20 patients aged 22–62 (mean age of 37) years with GSD type I, III and IX, for up to 5 years with serial measurements of bone turnover mark...

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...