Endocrine Abstracts

Aberrant pseudoexon inclusion is rarely recognised as a cause of human disease. Here we report two novel, compound heterozygous mutations in nicotinamide nucleotide transhydrogenase (NNT), one of which activates a pseudoexon, as the cause of familial glucocorticoid deficiency in two siblings. Whole-exome sequencing identified a single novel, heterozygous variant (R71X) in both affected individuals. Follow-up cDNA analysis identified the pseudoexon inclusion (p.P998_D9...

Background: The PAOLA study assessed the efficacy/safety of pasireotide LAR vs continued treatment with octreotide LAR/lanreotide Autogel in patients with inadequately controlled acromegaly. An exploratory objective was to measure changes in various associated biomarkers, including IGF1 and IGFBP2 (released from white fat cells and known to prevent insulin resistance), glucose and HbA1c.Methods: Adult patients (GH >2.5 μg/l and IGF1 >1.3&#21...

Introduction: Even though it is well known that long-term complications, such as renal insufficiency and brain calcifications can occur in patients with hypoparathyroidism (HPT), the risk of cardiovascular diseases still remains unclear.Objective: To perform a systematic assessment of cardiovascular function in a well-characterized cohort of patients with HPT compared to population-based controls.Methods: 133 patients with chronic ...

Background: Patients with complete androgen insensitivity syndrome (CAIS) who undergo gonadectomy have evidence of reduced bone mineral density (BMD) and perhaps, higher risk of fragility fractures. Because of this, hormonal replacement therapy (HRT), usually in the form of estrogen, is used as patients with CAIS have 46, XY genotypes having androgen receptor abnormalities making them resistant to the effects of androgen. Tibolone, a “selective tissue estrogenic activity...

Locus-specific databases (LSDBs) have been recently developed in response to the increasing number of genetic changes reported in the human genome. LSDBs have been created for several genes implicated in endocrine syndromes, for example MEN1, VHL, RET, GNAS, PRKAR1A and the SDH subunits. Mutations in AIP are found in about 20% of familial isolated pituitary adenoma (FIPA) patients.The aim of this proj...

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...

Circulating levels of prolactin are subject to acute and long-term regulation by many factors including oestrogen and dopamine. We have studied the regulation of prolactin promoter activity in living pituitary cells using transgenic Fischer rats in which reporter gene expression is regulated by the human prolactin gene locus (hPRL-d2EGFP). We have previously identified pulsatile prolactin transcription patterns in living lactotroph cells in fetal tissue, that became stabilised...

Background: Primary Aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Animal and in vitro studies have demonstrated that exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy and this may, partly, be mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in humans using contrast-enhanced cardiac MRI as well a...

Understanding how fate choices are made by multipotent progenitors during pancreas development is valuable information in the quest for regenerative medicine and cell therapy to treat diabetes mellitus. Pancreatic differentiation is well defined and understood in rodents however, human data are comparably scarce. Specifically, when human pancreatic progenitors are multipotent is unknown as are the epigenetic changes that these cells undergo during their differentiation to beta...

Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome. We aimed to characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis.Design: Cross-sectional comparative.Patients and methods: Of 27 Caucasian patients with classic 21HD (4–31 years); 27 sex-, age- and BMI-matched controls. Cli...