Endocrine Abstracts

Background: Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and controls the circulating free cortisol pool. Proteolytic cleavage by neutrophil elastase is proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. The CORtisol NETwork (CORNET) consortium found that genetic variation at a locus spanning SERPINA1 (encoding alpha-1 antitrypsin, A1AT, the endogenous inhibitor of neutrophil elastase) and SE...

Excess action of glucocorticoid hormones is implicated in metabolic disease and cognitive decline, 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) catalysing generation of active glucocorticoid hormones in tissues. The penetration rates and tissue-specific contribution of 11βHSD1 to glucocorticoid turnover were assessed using tracer kinetics. 9,11,12,12-d4-Cortisol (d4F) was infused (1.75 mg/day, 7 days) into C57Bl6/J male mice and mice lacking 11βHSD1 (n<...

Introduction: CBG is the main transport protein for glucocorticoids in blood. CBG gene is a member of the serine protease inhibitor family, located at chromosome 14q32. Inherited CBG deficiency (MIM 611489) is a rarely recessive disorder, and the phenotype associated includes low cortisol levels, presence of normal ACTH levels, hypotension and fatigue, although the exact pathophysiological mechanisms involved remain uncertain. We identified a family with a complex phe...

Background: Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development; however the relationship of childhood treatment with adult health outcomes is not established. We explored this by examining relationships between final height (FH) and cardiometabolic risk in CAH adults.Methods: Cross-sectional analysis of 65 men (80% salt wasting (SW) and 20% non-SW) and 134 women (74% SW and 26% non-SW), aged 18–69 years....

Background: Quality of life (QoL) has been variously reported as normal or impaired in congenital adrenal hyperplasia (CAH) adults. We found impaired QoL in UK CAH adults (Arlt et al. Journal of Clinical Endocrinology and Metabolism 2010 95 5110–5121) and now report the relationship between QoL (SF-36) and health outcomes in these patients.Methods: Cross-sectional analysis of 151 CAH adults with 21-hydroxylase defi...

A 59-year-old gentleman with schizoaffective disorder, treated with long-term lithium therapy and depot fluphenazine, underwent elective cystectomy and ileal conduit formation for transitional cell bladder carcinoma.Post operatively, he developed acute renal impairment, evidenced by a fall in eGFR from 68 to 26 ml/min per 1.73 m2. This resulted in accumulation of lithium to a toxic level of 1.82 mmol/l (0.4–1.0); despite stopping lithium,...

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...

Key circulating molecules that link the emerging role of vitamin-D to pediatric obesity and its co-morbidities remain unclear. To identify potentially involved regulators, this study analyzed plasma proteoma from obese children dichotomized by 25OH-vitamin D (25OHD) levels and upon vitamin-D3 therapy in 25OHD deficient subjects.A total of 42 obese children (M/F=18/24, bmi>95° centile) were selected and divided according to 25OHD levels into defi...

Introduction: Higher cortisol levels and, in particular, hyperactivity of the HPA axis might play a role in the development of MS at least in adults. Data on the pediatric age are scanty.Aim of our study was to evaluate ACTH and cortisol association with MS, its components, phenotypic parameters, family history of metabolic derangements in pediatric obesity.Methods: Cross-sectional study. 271 Caucasian overweight or obese children ...

Introduction: The risk association between the insulin like growth factor-1 (IGF1) and cardiovascular risk is inconclusive in adults and under-explored in the pediatric population. We aimed to investigate the associations between serum concentrations of IGF1 and cardiovascular risk factors in obese children and adolescents.Methods: Cross-sectional study. Clinical and metabolic evaluations including an oral glucose tolerance test (OGTT) were performed at ...