Endocrine Abstracts

Although life expectancy is increasing, deterioration in many tissues with age can substantially impair quality of life. Muscle loss and weakness, decreased bone density leading to fractures, insulin resistance leading to diabetic complications and cognitive decline increase substantially with age. These features are also seen in patients treated with high doses of glucocorticoids raising the possibility that glucocorticoids could be involved in the ageing process. However, ci...

Osteogenesis imperfecta (OI) is a rare but serious genetic disorder of bone leading to increased fragility and greatly increased susceptibility to fracture. Some patients experience additional problems such as abnormally formed teeth, progressive deafness and scoliosis. The condition is divided into various subtypes with types I and IV being the commonest, type 2 is lethal in utero and type 3 is associated with most disability and deformity. Patients with OI typically h...

Critical illness is associated with dramatic changes in the glucocorticoid axis. These changes occur at all levels of the axis, are most obvious in the increased serum levels of glucocorticoid but also occur within the tissue. Frank impairment of these responses (e.g. in Addison’s disease or with drugs that block adrenal hormone secretion) is associated with an adverse outcome but it has recently been suggested that many critically ill patients develop subtle abnormalitie...

Fibrous dysplasia (FD) is a relatively uncommon condition presenting with combinations of focal bone abnormalities, cutaneous hyperpigmentation and endocrinopathy. It is caused by a post-zygotic mutation in a G-protein coupled receptor (GNAS1) leading to constitutive activation of several hormone signaling pathways. Severely affected patients present in childhood with extensive bone lesions+endocrine disorder e.g. premature puberty (McCune–Albright syndrome) but less seve...

Background: There are over 650 liver transplants performed in the UK each year and about 5000 throughout Europe. After transplantation patients suffer from bone loss due to multiple factors. We present a unique case of severe Vitamin D deficiency resulting in life threatening hypocalcaemia following liver transplantation.Case: A 65-year-old Indian lady underwent an uncomplicated liver transplant, for hepatocellular carcinoma related to Hepatitis C. Pre a...

Therapeutic glucocorticoids are used in rheumatoid arthritis (RA) to reduce inflammation and bone destruction. We recently reported that primary synovial fibroblasts generate active glucocorticoids via expression of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme activates cortisol from inactive cortisone (and prednisolone from prednisone) and this activity is up-regulated by inflammation. We have now examined glucocorticoid metabolism in synovial tissu...

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...

Concerns have been raised that undergraduate medical education in Endocrinology/Diabetes (E&D) is not preparing students adequately for clinical practice. This project assessed trainer perceptions of the delivered D&E curriculum and identified areas for improvement. We surveyed E&D consultants at the 12 hospitals which accept students from our medical school using an online questionnaire. Emails were sent to 50 consultants. The response rate was 46% (23/50 recipien...

Human studies indicate that local glucocorticoid (GC) generation within osteoblasts plays a critical role in various bone diseases. Human osteoblasts express the enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) that converts inactive GCs (cortisone, dehydrocorticosterone) to their active counterparts (cortisol, corticosterone). This activation capacity critically depends on expression of a cofactor generating enzyme hexose-6-phosphate dehydrogenase. Enzyme expression ...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...