Endocrine Abstracts

Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are being developed to prevent cortisol regeneration from cortisone in liver and adipose tissue in type 2 diabetes (T2DM). However, the target patient group is uncertain. In obesity 11β-HSD1 activity is increased in adipose tissue but decreased in liver, as judged indirectly by plasma cortisol levels after oral cortisone administration. However, in T2DM, urinary steroid ratios suggest liver 11&#946...

Introduction: It is not known if non-alcoholic fatty liver disease (NAFLD) predates type 2 diabetes. We will study the prevalence of NAFLD in women with previous gestational diabetes (GDM), a population at ≥60% risk for the development of type 2 diabetes, while glucose tolerance is non-diabetic. It is not known if hepatic fat accumulation in NAFLD is disproportionate to fat accumulation in other tissues. We aim to study the association between fat in the liver and in tis...

Pancreatic endocrine tumours (PETs) have a low proliferation index and this partially accounts for their lack of response to chemotherapy. The assessment of proliferation rates relies largely on the use of markers such as Ki67 in patients, and uptake of DNA nucleotide precursors such as tritiated thymidine or 5-bromo-2-deoxyuridine (BrdU) in animals. Amongst these, BrdU is recognised to be the most reliable marker of cell proliferation as it allows the substitution of an endog...

D cells comprise 3–10% of the human endocrine pancreas and secrete somatostatin, which inhibits cell proliferation and hormone secretion. Pancreatic tumours secreting somatostatin are associated with the somatostatinoma syndrome, which is characterised by hyperglycaemia, cholethiasis, a low acid output and anaemia. We have examined for the presence of somatostatin secreting cells in pancreatic tumours from a multiple endocrine neoplastic type 1 (MEN1) knockout mouse model...

Sub-clinical Cushing’s syndrome has, in recent years, been described among diabetic populations but no consensus has emerged about the value of screening. We enrolled 201 consecutive diabetics attending clinic and 80 controls. Local ethics committee approval was obtained. Patients with at least 2 of the following 3 criteria were offered screening: HbA1c≥7%, BMI≥25 and history of hypertension or BP≥140/90. An 11 pm salivary sample was stored at room tempe...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, pancreas and pituitary. MEN1 is caused by germline inactivating mutations of the MEN1 gene which is located on chromosome 11q13 and encodes a 610 amino acid protein, menin. MEN1 tumours show loss of heterozygosity (LOH) of chromosome 11q13, and lack menin expression, consistent with a tumour suppressor role for MEN1...

Background: Aldosterone levels in plasma are reported to be associated with risk of hypertension. Aldosterone secretion from the zona glomerulosa is regulated acutely by the renin/angiotensin system and plasma potassium. The role of ACTH in regulation of aldosterone secretion is disputed.Aim: We have utilised a large population study of middle aged adults to test the extent to which acute aldosterone responses to ACTH are associated with cortisol respons...

Ligand binding by the calcium-sensing receptor (CaSR), which belongs to family C of the G-protein coupled receptor super-family, activates the phospholipase C-inositol triphosphate pathway and leads to an increase in intracellular calcium. CaSR inactivating mutations result in the hypercalcaemic disorders of familial benign hypocalciuric hypercalcaemia (FBHH) and neonatal severe primary hyperparathyroidism (NSHPT), whilst activating mutations result in the hypocalcaemic disord...

Mutations leading to haploinsufficiency of the dual zinc finger transcription factor GATA3 result in the hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome which is an autosomal dominant disorder. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Venous blood was obtained after informed consent, as approved by the local ethical committee, and leukocyte DNA extracted. GATA3 specific primers were used for PCR amplif...

Pituitary surgery frequently leads to one or more anterior pituitary hormone deficiencies but the incidence of GH deficiency is unclear. The aim of our study was to establish the incidence of GH deficiency in patients post hypophysectomy. Current NICE guidelines recommend GH replacement in severely GH deficient patients who have one or more other pituitary hormone deficiencies and diminished QoL by AGHDA.Thirty-five patients (M:F 15:20; age range 23&#150...