Endocrine Abstracts

Integration of genetics and epigenetics has emerged as a powerful approach to study cellular differentiation and tumourigenesis. The study of DNA methylation is of particular importance in cancer as causal involvement has been demonstrated and it is the most stable of all epigenetic modifications, making it a desirable marker for both early detection and treatment of tumours. Hypermethylation of CpG sites in gene promoter regions leads to decreased gene expression, if such a g...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids thus amplifying their intracellular actions. 11β-HSD1 deficiency or inhibition, which improve metabolic syndrome and attenuate atherosclerosis in vulnerable rodent strains, is a target for drug development. However, 11β-HSD1 also converts 7-ketocholesterol (7KC) (which accumulates in fatty tissues), to the potentially more atherogenic, 7β-hydroxycholesterol. Whether a...

The mouse knockout model for multiple endocrine neoplasia type 1 (MEN1) closely resembles the phenotype of the human disorder, with frequent development of tumours of the parathyroids, pancreas and pituitary. These tumours have loss of heterozygosity (LOH) of the Men1 locus and lack expression of the encoded protein (menin).The aim of this study was to investigate the feasibility of detecting pituitary tumours in heterozygous (Men1+/−...

The Hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by mutations in the dual zinc-finger transcription factor GATA-3. Gata3 heterozygous (+/−) knockout mice develop deafness, while Gata3 homozygous (−/−) mice, which are embryonically lethal at 11.5 to 12.5 days post-coitum (dpc), develop renal hypoplasia. The parathyroids have not been studied, and we therefore investigated these mice for ...

Context11-oxygenated C19 steroids have recently gained attention as markers of androgen control in congenital adrenal hyperplasia (CAH) due to 21hydroxylase deficiency (21OHD). However, they have not yet been systematically investigated in the context of different glucocorticoid (GC) replacement regimens and in particular not in patients receiving new modified-release formulations.MethodsCross-sectional singl...

BackgroundStandard glucocorticoid (GC) therapy in classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD-CAH) is often inadequate in controlling adrenal androgen excess, leading to GC over-exposure and poor health outcomes. A novel modified-release formulation of hydrocortisone (MR-HC, Chronocort® Diurnal Ltd. UK) has been shown to improve circulating adrenal androgen excess in 21-OHD-CAH. We investigated whether saliva and ...

BackgroundRoutine biochemical assessment in patients with congenital adrenal hyperplasia (CAH) includes measurement of serum 17–hydroxyprogesterone (17OHP), androstenedione (A4) and testosterone (T) and their metabolites in urine. Several studies have also described 11–oxygenated 19–carbon (110 × C19) steroids as a clinically relevant androgenetic source and highlighted their potential as markers for evaluation of adrenal androgen exc...

In Northern Ireland, the sole tertiary referral centre for pituitary disease which includes neurosurgery and endocrinology for ~1.9 million people, is based in the Royal Victoria Hospital, Belfast. A retrospective study has been commenced to examine clinical, biochemical, histopathological and radiological data for all patients operated on across an approximately 20 year period in Northern Ireland. Ethical approval was obtained from the Northern Ireland Biobank (study num...

BackgroundStructured lifestyle modification programmes are offered as first line treatment to patients referred to bariatric specialist services. We sought to describe changes in anthropometric and metabolic characteristics in a cohort of bariatric patients following completion of an eight-week, multidisciplinary group-based lifestyle intervention focussed on diet and physical activity.MethodsWe conducted a p...

Neuroendocrine neoplasms (NENs) are a heterogeneous tumour classification including indolent neuroendocrine tumours (NETs), aggressive neuroendocrine carcinomas (NECs). NECs and small cell lung cancer (SCLCs) are poorly differentiated tumours and life expectancy following metastatic diagnosis is less than 1 year. Currently, there are known variants in germline DNA that associate with bronchial and pancreatic NENs, but not intestinal. We conducted an exome-wide association stud...