Endocrine Abstracts

Within the synovium of patients with rheumatoid arthritis (RA), synovial fibroblasts generate active corticosteroids through expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In vitro, this enzyme is strongly up-regulated by pro-inflammatory cytokines such as tumour necrosis factor α (TNFα) and IL1β. In this study, we determined the relationship between inflammation and global 11β-HSD1 activity in vivo, in a clini...

Osteoporosis is a challenge facing children of all ages with a variety of health conditions and physical abilities. The reality of this challenge spurred the development of the child health program’s interdisciplinary bone health project team in a tertiary care in-patient pediatric hospital. The team’s goal was to develop protocols and tools to identify ‘at risk’ children and ultimately prevent fragility fractures in this group of children. The use of stand...

The steroid 17α-hydroxylase enzyme CYP17A1 exerts two distinct activities that catalyze conversion reactions at key branch points in steroidogenesis. CYP17A1 17α-hydroxylase activity is the key step in cortisol synthesis whereas CYP17A1 17, 20 lyase activity generates sex steroid precursors. Inactivating CYP17A1 mutations result in CYP17A1 deficiency (17OHD), a rare form of congenital adrenal hyperplasia that classically presents with combined glucocorticoid and sex ...

Hyperandrogenaemia and polycystic ovary syndrome (PCOS) are common in women with Type 1 diabetes, but it is not known if they contribute to increased cardiovascular risk. We aimed to compare associations between androgen levels, lipid variables and early atherosclerosis in reproductive-age women with and without T1DM. 87 (16 with PCOS) women with T1DM (mean±SD; age 28.7±6.1yrs, BMI 25.4±4.4kg/m2), and 87 (16 PCOS) nondiabetic women (mean±SD; age ...

BackgroundPolycystic Ovary Syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. The main components are hyperandrogenemia and oligo-/amenorrhea. The pathophysiology of PCOS is not fully understood which is why no causal treatment options are available. A multitude of observational studies demonstrated elevated C-reactive protein (CRP) levels in patients with PCOS compared with weight-matched controls. CRP is a sensitive ...

Objectives: To assess antenatal and individual-level predictors of thyroid function across two longitudinal cohorts of children.Methods: Data were taken from two cohorts i) CATSII: 5-10 year-old children enrolled in the CATS (Controlled Antenatal Thyroid Screening) study II from the UK ii) ‘PAX8’: Children from the ENID (Early Nutrition and Immune Development) trial, a pregnancy and infant supplementation trial in The Gambia (Africa) recruited ...

Introduction: Multi-modal therapy for adrenocortical carcinoma (ACC) includes surgery, therapy with the adrenolytic agent mitotane and systemic chemotherapy. Achievement of therapeutic mitotane concentrations (≥14 mg/l) has been related to improved outcomes.Aim: To evaluate the effectiveness of a defined* high dose protocol mitotane therapy in patients with advanced ACC (stages III and IV).Methods: Review of patients presenti...

Background: Bone toxicity and more specifically Radiotherapy Related Insufficiency Fractures (RRIFs) are common late effects of pelvic radiotherapy, associated with increased morbidity and reduced quality of life, while their cost to the health system is currently unknown. The mechanisms underlying RRIFs are not well understood. Effective preventive techniques and management pathways need to be developed and validated with robust clinical and health economic analyses. The RadB...

Background: The gonads are the major source of classic androgens during reproductive years. Additionally, the adrenal gland produces precursors for both classic and 11-oxygenated androgen biosynthesis, with androgen activation predominantly occurring in peripheral target tissues of androgen action. We used liquid chromatography-tandem mass spectrometry to profile classic and 11-oxygenated androgens in serum and saliva across the adult age range and assessed diurnal as well as ...

Chronic wounds (e.g. diabetic foot ulcers) have a major impact on quality of life, yet treatments remain limited. Glucocorticoids impair wound healing; preclinical research suggests that blocking glucocorticoid activation by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves wound repair. This investigator-initiated double-blind, randomised, placebo-controlled parallel-group phase 2b pilot trial investigated efficacy, safety and feasibility of 11&...