Endocrine Abstracts

Short synacthen tests (SST) are used to investigate patients with suspected HPA pathology and a rise of serum total cortisol > 550nmol/L is accepted as demonstrating sufficient cortisol reserve. However, cortisol is 80% bound to cortisol binding globulin (CBG) and therefore abnormal values of CBG can influence serum total cortisol used to interpret dynamic tests of the HPA axis. The free cortisol index (FCI) is a surrogate marker for serum free cortisol and is defined as s...

Background: Cardiofaciocutaneous (CFC) syndrome is a rare disorder characterised by multiple abnormalities including congenital heart disease, craniofacial dysmorphology, ectodermal abnormalities, developmental delay, and epilepsy. Case reports of growth hormone (GH) deficiency, hyperprolactinemia, and precious puberty have been reported in association with CFC syndrome. A recent case series and gene knockout study highlighted the mechanistic role of CFC syndr...

Chronically elevated glucocorticoid (GC) level impairs cognition. In rodents, elevated plasma GC levels, prior to an inflammatory challenge, potentiates neuroinflammation that is abolished by GR but not MR antagonism. 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1) increases intracellular GC levels by regenerating active GCs from inert forms. Inhibition/deficiency of 11β-HSD1 is protective against age-related cognitive decline presumably by lifelong reduced b...

Background: Silver-russell syndrome (SRS; OMIM 180860) is a genetically and clinically heterogeneous low birthweight syndrome characterised by poor postnatal growth and a number of variable dysmorphic features. Small-for-gestational age infants in general have an increased risk of metabolic complications, some initially occurring in late childhood and adolescence.Objective and hypotheses: To identify (a) response to GH based on genotype and (b) developme...

The late gestation increase in glucocorticoid action promotes the structural and functional maturation of the fetal heart. Metabolic maturation of cardiomyocytes involves a switch from glucose utilization as a fuel source to fatty acid (FA) oxidation. In fetal cardiomyocytes, glucocorticoids induce expression of PGC1a (a master regulator of mitochondrial capacity), lipin1 and KLF15 (genes involved in FA oxidation). We hypothesized that glucocorticoids promote the metabolic swi...

Specific variations in the human glucocorticoid receptor (GR) gene associate with increased cardiovascular disease risk. GR signalling is essential for cardiac maturation in utero and adult mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice) have cardiac hypertrophy, fibrosis and impaired function. Intriguingly, levels of left ventricle (LV) mRNA encoding the mineralocorticoid receptor (MR), which is pro-fibrotic in heart, rise postnatally ...

Background: The short Synacthen test (SST) is the most widely used dynamic assessment of adrenal reserve. In some situations, the SST may be difficult to perform. Random basal cortisol levels could provide an alternative screening assessment to rationalize which patients need dynamic testing. This is highly clinically relevant, given the large numbers of patients taking prescribed glucocorticoids who are at risk of iatrogenic adrenal suppression.Methods:...

Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accu...

Glucocorticoids (GCs) are highly effective anti-inflammatory drugs, however their use is limited by serious side effects. We have previously shown that 5αTHB binds GC receptor (GR) and suppresses inflammation in vitro and in vivo, without affecting metabolism. Here the underlying molecular mechanisms were explored in cell models of ligand-induced GR phosphorylation, nuclear localisation and gene transcription. Data are mean±S.E.M. (th...

Context: Hydrocortisone day curves (HCDC) are used to monitor hydrocortisone replacement by obtaining serum samples to measure cortisol levels throughout the day. Salivary measurement of free cortisol offers a non-invasive alternative to serum measurements.Objective: To validate salivary cortisol measurement as an alternative method to assess the adequacy of hydrocortisone replacement in patients with hypoadrenalism.Setting, patien...