Endocrine Abstracts

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

5α reductases 1 and 2 (SRD5A1 and SRD5A2) metabolise cortisol into inactive 5α-dihydrocortisol contributing to the regulation of cortisol availability in addition to their established role in the generation of dihydrotestosterone from testosterone. Dutasteride and finasteride are commonly prescribed to patients with benign prostatic hyperplasia but their potential metabolic effects have only recently been identified. Dutasteride inhibits both SRD5A1and SRD5A2 whilst ...

Introduction: A breech presentation occurs in 3–5% of all full-term pregnancies and is associated with increased risk of maternal and foetal morbidity. Factors known to increase the risk of breech presentation include prematurity, low birth weight and multiple pregnancies. Recent studies suggest maternal thyroid hormone deficiency in late pregnancy may also be a risk factor. Our study aims to assess if a breech presentation at 36 weeks gestation in a healthy singleton coh...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive glucocorticoid to their active form (cortisone to cortisol in humans, 11-dehydrocorticosterone (11-DHC) to corticosterone in mice), and is dependent upon the presence of cofactor NADPH generated by the enzyme hexose-6-phosphate (H6PDH) for its activity. The 11β-HSD1/H6PDH system is implicated in the pathogenesis of the metabolic syndrome by generating tissue specific glucocorticoid excess. The ...

The epidemic of obesity, insulin resistance and type 2 diabetes has heightened the need to understand the mechanisms that contribute to their pathogenesis. Endogenous glucocorticoid (GC) production and metabolism have been implicated based upon parallels with Cushing’s syndrome. The interaction between GC metabolism and insulin sensitivity in the context of significant weight loss has not been explored. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that gen...

Introduction: Patients with adrenal insufficiency (AI) (primary (PAI), secondary to pituitary disease (PIT) and congenital adrenal hyperplasia (CAH)) have reduced life expectancy with reported standardized mortality ratios of ~2:1 but given the rarity of AI, the underlying explanation remains largely unknown.Objective: To evaluate patient characteristics, prevalence of concomitant conditions and hospitalization incidence in patients with AI compared to a...

Background: Twice-daily formulation of pasireotide, a pituitary-directed therapy, is approved for treatment of Cushing’s disease. Here we present data from a phase III study designed to evaluate the more convenient once-monthly long-acting release (LAR) formulation of pasireotide (approved for acromegaly) in patients with Cushing’s disease.Methods: Patients with persistent, recurrent, or de novo Cushing’s disease (not candidates for surger...

Introduction: The clinical outcome of patients with adrenal insufficiency (AI) has been shown to be less favorable than previously thought. Clinical studies have shown increased mortality, reduced cardiovascular and skeletal health and compromised quality of life, but the impact of this upon healthcare burden is unknown. This research utilised real-world evidence to compare comorbidities, healthcare utilization and expenditures in patients with AI.Method...

Introduction: No consensus guidelines currently exist as to the optimal glucocorticoid regimen in adrenal insufficiency (AI). In clinical practice physicians utilise a number of different glucocorticoids, usually administered in several doses throughout the day.Methods: The EU-AIR registry is a European multinational, multicentre, prospective, observational study sponsored by Shire inclusive of all patients with AI irrespective of aetiology. We analysed ...

Introduction: During recent years many authors have advocated lower hydrocortisone doses in patients with primary adrenal insufficiency (PAI) mainly due to worries for non-physiological effects like increased cardiovascular risk and bone resorption, but very little attention has been drawn to fludrocortisone dosing. Our main hypothesis was that that the higher hydrocortisone dose, the lower the fludrocortisone dose and vice versa.Design: The Eur...