Endocrine Abstracts

The rate limiting steps of hepatic glucocorticoid clearance are via A-ring reduction by 5α- and 5β-reductases. Our recent in vitro studies suggested that products of 5α-reduction (eg 5α-tetrahydrocorticosterone) can activate glucocorticoid receptors and hence may contribute to glucocorticoid action in liver. Here we compared the effects of administering 5α-tetrahydrocorticosterone (5αTHB) in vivo with those of corticosterone (B)....

Objective: To investigate a family with the unusual combination of Multiple Endocrine Neoplasia (MEN1) and the McCune-Albright syndrome for mutations of the MEN1 and GNAS1 genes. MEN1 is an autosomal dominant disorder characterised by parathyroid, pancreatic and pituitary tumours whereas the McCune-Albright syndrome is a sporadic disorder characterised by polyostotic fibrous dysplasia, skin pigmentation and hyperfunctioning endocrine tumours.<p class="abstext...

Introduction: Echocardiographic studies in patients with primary hyperparathyroidism (PHPT) suggest that up to half of patients have left ventricular dysfunction and an increased risk of congestive heart failure that improve after parathyroidectomy. The cardiac hormone B-type natriuretic peptide (BNP) is an independent risk marker for heart failure.Methods: Prospective cohort study of consecutive unselected patients with biochemical diagnosis of PHPT. Pl...

PPARgamma-agonists improve insulin sensitivity and discourage visceral fat accumulation but mechanisms remain uncertain. In rodents, PPARgamma-agonists downregulate 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) in adipose tissue (AT), thereby potentially decreasing intra-adipose glucocorticoid (GC) concentrations. We tested whether PPARgamma-agonists regulate 11b-HSD1 in humans, and if their insulin-sensitising effect is GC-dependent.12 healthy m...

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose, and skeletal muscle. ABCC1 is a transmembrane ‘drug-resistance’ transporter expressed in adipose tissue and skeletal muscle with previously unknown physiological function. We recently showed that ABCC1 modulates intracellular GC concentrations and action in adipose. Here, we tested the hypothesis that Abcc1 regulates GC concentrations in skeletal mu...

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose and skeletal muscle. GC access to corticosteroid receptors in these tissues is regulated e.g. by pre-receptor metabolism. We recently identified a role for ABCC1, a transmembrane ‘drug-resistance’ transporter, as a GC exporter which limits intracellular GC concentrations and action in adipose tissue. Here, we tested the hypothesis that ABCC1, which i...

Background: Polycystic ovary syndrome (PCOS) is a heterogenous condition that affects approximately 12% of females. The diagnosis can be complex and biochemistry tests are routinely relied upon to help identify hyperandrogenaemia and to exclude other conditions. However, although national and international guidelines advocate the use biochemistry tests, little information is provided as to which tests should be used and which other endocrinopathies should be excluded.<p cl...

Background: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the differential diagnosis of Cushing’s syndrome and the investigation of adrenal incidentalomas. However, diagnostic performance of the test relies on accurate methods to quantitate cortisol in serum. Although the variable performance of serum cortisol immunoassays has been well-documented, little has been published on their performance following the ONDST.Aims...

Background: Diagnosis of adrenal hypofunction requires a high index of suspicion. A frequent cause is iatrogenic glucocorticosteroid prescribing hence the need for a clinical review after a prolonged course.Aim: A review of glucocorticosteroid prescribing and auditing SST outcomes in a large private hospital.Methods: Electronic records over an 18 month period were analysed for SST results, patient demogra...

Heterotrimeric G-proteins are important molecular switches that transduce extracellular ligand-binding at G-protein-coupled receptors (GPCRs) to intracellular signals. G-protein alpha-subunits (Gα) have two domains, a helical and GTPase domain, which provide structural stability and mediate GTPase activity, respectively. Gain-of-function Gα mutations cause endocrine conditions including McCune-Albright Syndrome, due to Gαs mutations, and a...