Endocrine Abstracts

Introduction: Data on the impact of TBI on the HPAA are limited. This study investigates the HPAA in BMT-survivors and non-BMT controls using overnight serum cortisol profiles and midnight/9am ACTH levels.Subjects (N=35): N=14, child (7), adult (7) controls, N=21 child (7), adult (14) BMT-survivors (TBI dose 12.0-14.4Gy). None had had treatment with corticosteroids in the last year.Method: Subjects rested for 3...

Introduction: Growth hormone deficiency (GHD) after cranial irradiation (CRI) is time, dose and fraction dependent. TBI (12–14.4Gy) involves low dose CRI, and skeletal irradiation causing further adverse growth effects. We present baseline data from a prospective study of GH treatment.Subjects N=25: We studied 13 BMT survivors (all had TBI, 3 also had CRI <18Gy), and 12 non-BMT subjects investigated for GHD. Both groups contained y...

Glucocorticoid (GC) production rates are elevated in obese, insulin resistant individuals. We and others have demonstrated decreased hepatic cortisol regeneration through reduced 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity that converts inactive cortisone to cortisol. In addition, there is enhanced cortisol clearance by A-ring reductases, (notably 5α-reductase). We have argued that these changes drive the hypothalamo-pituitary–adrenal axis a...

In peripheral target tissues, levels of active glucocorticoid hormones are controlled by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyses the reduction of cortisone to cortisol within the endoplasmic reticulum. For functional 11-ketoreductase activity, 11β-HSD1 requires the NADPH-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH). Loss of 11-ketoreductase activity results in increased cortisol clearance and activation of the HPA axis wi...

Patients with glucocorticoid excess develop a phenotype characterized by central obesity, however, the impact of glucocorticoids upon the processes that regulate lipid accumulation has not been fully explored. We hypothesize that intracellular generation of cortisol from cortisone by 11b-hydroxysteroid dehydrogenase type 1 (11bHSD1) is an important regulator of lipid metabolism.In adipocytes, acetyl-CoA carboxylase 1 and 2 (ACC1/2) convert acetyl-CoA to ...

Background: Adrenal insufficiency is a well-recognised feature of congenital adrenal hyperplasia (CAH).CAH is commonly treated with oral steroid replacement, taken 2–3 times a day, at doses that aim to reproduce normal diurnal variation. Though acceptable for most patients, this does not control others, resulting in high levels of 17-hydroxyprogesterone-acetate (17OHP), ACTH, and the need for increased doses of steroid replacement, with associated c...

The CYP11B1 and CYP11B2 genes encode 11β-hydroxylase and aldosterone synthase, which catalyse the production of cortisol and aldosterone, respectively, and have been implicated in the development of hypertension. For this study, we wished to investigate the role of microRNAs (miRNAs), a novel class of post-transcriptional gene regulators. To that end, we generated a profile of human adrenal miRNAs to study, and then investigated the action of one adrenal miR...

Osteosarcoma (OS) is an aggressive malignant tumour of osteoblasts occurring predominantly in children and young adults. Despite chemotherapy relapse is common and mortality remains ~50%. Non-transformed osteoblasts are highly sensitive to glucocorticoids which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme powerfully inactivates cortis...

Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD, is highlighted by patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inacti...

Severe growth hormone (GH) deficiency in adults is associated with adverse changes in quality of life (QoL), body composition and cardiovascular risk profile. NICE guidance restricts GH replacement in the UK to those with impaired QoL, defined by a score of >11 in the QoL-AGHDA questionnaire.Aims: To assess whether the NICE guidance differentiates other clinical or biochemical features in GH deficient adults.Patients and...