Endocrine Abstracts

Introduction: Primary hyperparathyroidism (PHPT) affects 0.3% of the population. It is characterised by hypercalcaemia with an inappropriately high parathyroid hormone level. The majority of patients with primary hyperparathyroidism are asymptomatic and are diagnosed following an incidental finding of hypercalcaemia. Symptomatic disease is related to hypercalcaemia and can present with complications such as renal calculi and osteoporosis. Parathyroidectomy is the treatment of ...

Introduction: Aldosterone is a potent adrenal steroid hormone which regulates renal sodium reabsorption and potassium secretion. Clinically, measurement of aldosterone is important to identify patients with primary hyperaldosteronism, and has traditionally been performed by immunoassay. The specificity of immunoassays is often poor due to antibody cross reactivity to other structurally related steroid hormones, resulting in falsely elevated concentrations. To overcome these li...

We have previously investigated the ability of glucocorticoids secreted by the adrenal cortex to directly influence gonadal function. In contrast, the primary aim of the present study was to assess whether increased progesterone output from the corpus luteum on day 14 of the ovine oestrous cycle can alter adrenal metabolism (and hence output) of cortisol relative to oestrous cycle day 5. Since cortisol-cortisone inter-conversion by the cloned 11β-hydroxysteroid dehydrogen...

Glucocorticoids (Gc) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to treatment between individuals and over time. Generating a reversible model of Gc resistance in vitro that will mimic the cellular microenvironment in vivo is critical in (i) defining biomarkers that predict patient steroid responsiveness; (ii) provide a model to screen new GR modulators capable of potentiating GR ...

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...

Glucocorticoids (GCs) are used extensively in the treatment of inflammatory disease. Unfortunately, as GC act on virtually every organ system they also carry a broad range of serious side-effects which limits their clinical use.The structure of the bound GC strongly impacts the final conformation of the glucocorticoid receptor (GR) and thereby dictates downstream events. Designing drugs with different GR binding properties therefore offers a plausible ro...

Rheumatoid arthritis (RA) is a common chronic systemic inflammatory disease. Several new therapies exist for RA but long-term patient management remains problematic.We have discovered that hypoxia, a characteristic of inflamed tissues, potently inhibits glucocorticoid (Gc) sensitivity. This effect is mediated, in part by HIF1α, whose activity is induced in hypoxia. HIF1α gene expression is also induced in primary peripheral blood mononuclear ce...

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...

Pregnancy complications such as fetal growth restriction are associated with abnormal placental cell (cytotrophoblast) proliferation and apoptosis. Regulation of these events is unclear but recently we have used a placental explant model to demonstrate that IGFs influence cytotrophoblast kinetics and demonstrated that the protein tyrosine phosphatase (PTP) SHP-2 is required for IGF actions in the placenta. However, SHP-2 accounts for only 20% of total PTP activity, suggesting ...

Clinical guidance recommends titrating the dose of metyrapone against serum cortisol concentrations. These serum samples are usually measured by immunoassays; however it has been well documented that there are interferences in these assays in patients with altered steroid metabolism due to a pathological process or drug treatment. The increasing availability of mass spectrometry (MS) assays for steroid hormones may circumvent this issue and assays that measure multiple steroid...