Endocrine Abstracts

Background: Novel pathogenic mechanisms involving replicative and oxidative stress have recently been described in familial glucocorticoid deficiency (FGD); including mutations in NNT. NNT supplies high concentrations of NADPH needed by the glutathione and thioredoxin anti-oxidant systems to detoxify mitochondrial H2O2.Six patients, from a consanguineous Kashmiri family, were diagnosed with glucocorticoid deficiency between...

Introduction: Pasireotide normalized or reduced UFC in patients with Cushing’s disease in a large, 12-month study. This analysis evaluates the effects of pasireotide on the signs/symptoms of Cushing’s disease according to the degree of UFC control.Methods: Adult patients (n=162) with persistent/recurrent or de novo Cushing’s disease were randomized to pasireotide 600/900 μg s.c. bid. Dose titration (max: 1200 μg...

Introduction: Patients with Cushing’s disease (CD) have an increased risk of hypertension (HTN). phase III data have shown that pasireotide leads to rapid reductions in UFC levels and significant improvements in CD symptoms. We now present further analyses of these data, evaluating the effects of pasireotide on HTN in patients with CD.Methods: Patients with persistent/recurrent or de novo (if not surgical candidates) CD and UFC≥1.5 time...

Glucocorticoid treatment in congenital adrenal hyperplasia (CAH) is a continuous challenge, with even the experienced clinician struggling to strike the right balance between glucocorticoid over- and undertreatment. There is no consensus on monitoring of glucocorticoid therapy in adults with CAH. Some recommend a serum 17-hydroxyprogesterone (17OHP) target range of 12–36 nmol/l prior to glucocorticoid morning dose. Here we investigated the value of serum and urinary stero...

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

Phaeochromocytomas (PHAEO)/paragangliomas (PGL) are neuro-endocrine tumours. They may present sporadically or as the primary abnormality in a number of familial syndromes. Advances in molecular genetics have led to the identification of several PHAEO/PGL predisposing genes including VHL, NF1 and RET. Mutations in the genes encoding the subunits of Succinate Dehydrogenase (SDH) have also been reported. We describe the phenotype of a cohort of patients with a Succinate Dehydroge...

Using functional MRI, we examined how regional brain activity varies with nutritional state when viewing food pictures of different caloric density and appeal.Eighteen non-obese healthy volunteers (BMI 22.2±0.5 kg/m2, age range 19–36 years, 8 male) were studied on 2 separate mornings after an overnight fast (mean±S.E.M. 15.5±0.3 h) or when fed (1.2±0.1 h after breakfast, food intake 45±4% of estimat...

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impair...

Introduction: Compared to ethnically European men, Pakistani origin men living in the UK have a lower circulating total and free testosterone level, corresponding with greater central adiposity and higher insulin resistance. Within a South Asian group we have now examined the effect of migration to the UK on male testosterone level.Methods: Circulating testosterone concentration was measured by automated immunoassay in 97 Gujarati males resident in India...

Background & Objective: Pseudohypoparathyroidism (PHP), a heterogeneous condition, classically causes parathyroid hormone (PTH) resistance. PHP1a is caused by heterozygous inactivating mutations on the maternally derived GNAS allele. PHP1b results from methylation defects at the GNAS imprinted gene cluster, which are either sporadic, or familial, normally associated with maternally inherited intragenic STX16 deletions. We investigated the presentation, phenotype, ...