Endocrine Abstracts

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...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing’s syndrome (glucocorticoid excess) - notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol, and thus amplifies local glucocorticoid action. We hypothesise that 11β-HSD1 expression is neg...

Introduction: The repercussions of long-term exposure to low level mixtures of endocrine disrupting compounds (EDCs) which are present, ubiquitously, in the environment are not well understood. Heat-treated sewage sludge, an EDC-rich product used as fertiliser, has been shown to compromise testicular and ovarian development. However, to date, there has been limited investigation in exposed animals of the adrenal glands, the steroid hormone products of which play key roles in f...

Introduction: Survivors of childhood BMT/TBI have increased cardiovascular morbidity and GH deficiency (GHD). We aimed to investigate the relationship between cardiovascular risk and GHD and GHTx in BMT/TBI survivors.Methods: BMT/TBI survivors (n=36) and non-BMT control subjects (n=19) were sub-divided according to GH status assessed by insulin tolerance test: i) survivors with untreated GHD (N=18,11M), ii) survivors on GHTx (N</i...

Hereditary stomatocytoses, including cryohydrocytosis, are anaemias in which the erythrocyte membrane has increased permeability resulting in electrolyte leakage and thus haemolysis. Many forms and underlying molecular mechanisms exist. GLUT1 is present in the blood–brain barrier and erythrocytes, but GLUT1-deficiency does not usually affect erythrocytes. We describe a child with a stomatocytosis due to a SLC2A1 mutation presenting with hyperkalaemia, liver disease...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Differences in gene expression between omental (om) and subcutaneous (sc) adipose have been described, but molecular mechanisms underpinning differences in adipose biology are not known. Patients with glucocorticoid excess, Cushing’s syndrome, develop a phenotype characterized by central obesity. We have characterized the regulation of lipogenesis by gluco...

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...

Objective: The past 2 decades have seen advances in the surgical management of Cushing’s disease (CD). Our aim was to meet the need for current data on clinical features, long-term outcomes, and prognostic indicators.Patients and methods: We conducted a retrospective study of 71 patients treated by trans-sphenoidal surgery (TSS) for CD. All patients were operated on by the same surgeon in a single centre between 1988–2009. Diagnosis was confirm...

Glucocorticoid (GC) excess (Cushing’s syndrome) is characterized by central obesity, insulin resistance and in up to 20% of cases, non-alcoholic fatty liver disease (NAFLD). NAFLD is a progressive spectrum of disease ranging from hepatic steatosis to steatohepatitis, fibrosis and cirrhosis. Many processes contribute to lipid accumulation within heaptocytes including de novo lipogenesis which includes the rate-limiting carboxylation of acetyl CoA to malonyl-CoA by a...