Endocrine Abstracts

Dent’s disease, due to mutations in the chloride/proton antiporter, CLC-5, represents one form of familial hypophosphataemic rickets. Dent’s disease patients also have: low-molecular-weight-proteinuria; hypercalciuria with nephrolithiasis and renal failure; and urinary loss of parathyroid hormone and vitamin D-binding protein, due to defective receptor-mediated endocytosis within the renal proximal tubule. However, there is variability in these clinical phenotypes su...

Neck ultrasound (US) can facilitate minimally invasive parathyroidectomy by providing fine anatomical detail of enlarged parathyroid adenomas in patients with primary hyperparathyroidism (PHPT). The role of neck MRI in US negative/equivocal cases remains unclear. We aimed to evaluate the performance of neck MRI in parathyroid tumour localisation in the setting of negative or equivocal neck US.We performed a retrospective review of a consecutive series of...

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...

Receptor-mediated endocytosis (RME), involving megalin and cubilin, mediates renal proximal-tubular reabsorption of glucose, proteins and hormones including insulin, parathyroid-hormone and vitamin D. RME disruption occurs in Dent’s disease patients with mutations of the chloride/proton antiporter, CLC-5, who suffer from low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis and renal failure. To further investigate the RME role of CLC-5 we established conditio...

Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a mode...

5alpha-Reductase1 (5aR1) catalyses glucocorticoid metabolism, potentially modulating glucocorticoid clearance and therefore affecting the activity of the hypothalamic–pituitary–adrenal (HPA) axis. 5aR1 is up regulated in obesity associated with activation of the hypothalamic–pituitary–adrenal (HPA) axis. Here we investigated if inhibition of 5aR1 impairs glucocorticoid clearance and suppresses the HPA axis.Age-matched male and female ...

Hypopituitary patients are at increased vascular risk. This may be partly attributable to changes in insulin action. It has been suggested that the addition of dehydroepiandrosterone sulphate (DHEAS), which is low in patients with secondary hypoadrenalism, to routine replacement may have beneficial effects on glucose metabolism. Previously, patient populations and techniques used to assess insulin action varied and overall results have been conflicting.W...

Activating mutations of the calcium sensing receptor (CaSR) result in autosomal dominant hypocalcaemia with hypercalciuria (ADHH), in which patients may also suffer from polyuria, polydipsia, nephrocalcinosis, renal impairment, and ectopic calcification. A mouse model, Nuf, with an activating Leu723Gln CaSR mutation has been reported to develop the features of ADHH as well as cataracts that consist of dot nuclear opacities, which have not been described in ADHH patients...

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, pancreas and pituitary. The MEN1 gene, which is located on chromosome 11q13 and encodes a 610 amino acid protein (menin), belongs to the class of tumour suppressors. To investigate the role of menin in tumour suppression, three different mouse models have been generated through targeted disruption of the Men1 gene. ...

Introduction: Adult growth hormone deficiency (AGHD) is associated with target organ insensitivity to parathyroid hormone (PTH) and abnormal PTH circadian rhythm. In aging women with established osteoporosis, GH and insulin like growth factor -1 (IGF-1) concentrations are low and administration of GH has been shown to increase bone turnover and bone mineral density (BMD), but the mechanisms remain unclear. Consequently we investigated the effects of declining GH and IGF-1 conc...