Endocrine Abstracts

Objectives and methods: The HORIZON-PFT is a multinational, 3-year, randomized, double-blind, placebo-controlled trial evaluating the potential of once-yearly zoledronic acid (ZOL) 5 mg, infused over 15 minutes, to decrease risk of fracture in 7736 postmenopausal osteoporotic women 65–89 years of age.Results: Treatment with ZOL 5 mg resulted in significant relative risk reductions in morphometric vertebral fracture of 70% vs PBO (3.8% vs 12.8%; 95% ...

Central obesity is strongly associated with sub-clinical inflammation, insulin resistance (IR) and type 2 diabetes mellitus (T2DM), but the intracellular mechanisms involved in the pathogenesis of central obesity remain unclear. Recent studies have implicated NFκB and c-jun N terminal kinase (JNK) as central molecules linking insulin action and inflammation in mice. As such we examined (1) the inflammatory intracellular signaling pathways involving NFκB, JNK as a pot...

Subpopulations of beta cells dictate overall ‘pacing’ of insulin secretion across the islet and therefore the control of glycaemia. Functional beta cell subpopulations also exist in human islets and have an altered subtype distribution in type 2 diabetes. However, the molecular control of the establishment and maintenance of beta cell hierarchy is poorly understood. We hypothesised that the epigenome would govern this heterogeneity. We have identified a novel subpopu...

Aim: To assess whether patients on glucocorticoids understand how to manage their medication in the event of intercurrent illness.Background: Studies have shown that, after as little as two weeks of glucocorticoid treatment, 10% of patients have adrenal suppression and it can take one year or longer for adrenal function to recover. With 7 out of 1000 people in the general population prescribed glucocorticoids, there is a large group at risk of adrenal cr...

Maternal programming increases the risk of alterations in the offspring’s HPA axis. Previously we showed that maternal undernutrition in sheep induces epigenetic changes in the glucocorticoid receptors (GR) within hypothalamic energy balance pathways, without affecting HPA axis GR. However, these studies focussed on fetal tissues1. Here, we investigated whether GR is epigenetically altered in the HPA axis of adult offspring to determine the status of the pathwa...

Epigenetic reprogramming including altered transcription factor binding and altered patterns of chromatin and DNA modifications are now accepted as the hallmark of aggressive cancers. We show that global changes in chromatin structure and chromatin accessibility in prostate tumour tissue can define castrate-resistant prostate cancer and be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor overexpression alone, w...

The European Registry on Cushing’s Syndrome (ERCUSYN) is designed to collect prospective and follow-up data on patients with Cushing’s syndrome (CS) and currently (Sep 2013) includes 1006 patients (804 F, 202 M; mean age (+S.D.) 44.7±13.3 years) from 57 centers in 28 countries.Six hundred and sixty one (66%) had pituitary-dependent CS (PIT-CS), 242 (24%) adrenal-dependent CS (ADR-CS), and 103 (10%) CS from other etiologies, ...

Familial hypocalciuric hypercalcaemia (FHH) comprises three types: FHH1, FHH2, and FHH3, which are due to mutations of the calcium-sensing receptor (CaSR), G-protein α 11 subunit (Gα11), and adaptor protein-2 sigma subunit (AP2σ), respectively. The aims of this study were: to assess for genotype–phenotype correlations among the three reported FHH3-causing AP2σ mutations, which all involve the Arg15 residue, and comprise Arg15Cys, Arg15His, and Arg15Leu...

PARADIGHM is an actively recruiting, prospective, observational registry (NCT01922440/EUPAS16927). The primary objective is to evaluate the safety and effectiveness of recombinant human parathyroid hormone, rhPTH(1-84), treatment in patients with chronic hypoparathyroidism under routine clinical care. The secondary objective is tocharacterize the clinical course of chronic hypoparathyroidism under conditions of routine clinical practice. At enrollment, registry inclusion crite...

Background: New effective therapies are needed to improve the survival of patients with metastatic pancreatic NETs (pNETs). RABL6A is a novel oncogenic driver of pNET pathogenesis. Kinome and phosphoproteome analyses of proliferating (RABL6A-positive) pNET cells, vs arrested (RABL6A-knockdown) controls, demonstrated that cyclin-dependent kinase 4 and 6 (CDK4/6) and MEK kinases are actionable drug targets in growing pNET cells. In agreement, published studies of patient pNETs b...