Endocrine Abstracts

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&...

Active androgens exert immunomodulatory actions at sites of inflammation and lower levels are implicated in the increased incidence of rheumatoid arthritis (RA) in females. However, inflammatory regulation of intracrine androgen metabolism within cell populations at sites of inflammation remain poorly defined. In this study we characterised immune and stromal cell androgen metabolism in RA patients and assessed their functional significance. Using the online Accelerating Medic...

Introduction: Monitoring glucocorticoid (GC) replacement in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) remains challenging. There are disease-specific patterns in the plasma and urinary steroid profiles in 21OHD, a key role being played by the 11-oxygenatedC19 androgens. Aim: To explore the urinary steroid profile in 21OHD in relation to treatment and plasma steroids. Methods: Partic...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating NNT mutations lead to isolated primary adrenal insufficiency, suggesting a selective vulnerability of adrenoc...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating NNT mutations lead to isolated primary adrenal insufficiency, suggesting a selective vulnerability of adrenoc...

Background: Benign adrenal tumours are discovered in 3-10% of adults and can be non-functioning (NFAT) or associated with adrenal hormone excess, most frequently mild autonomous cortisol secretion (MACS) defined by the failure to suppress cortisol after 1 mg dexamethasone overnight but lack of distinct signs of Cushing’s syndrome (CS). We found that MACS increases the prevalence and severity of type 2 diabetes and hypertension and primarily affects women (Ann Int Med. 202...

The International Diabetes Federation estimates that type 2 diabetes mellitus (T2DM) will affect 642 million people by 2040. Chronically inflamed, hypoxic wounds are common in T2DM and represent a global unmet clinical need. Each year, diabetic foot ulcers cost the NHS £650 million and cause 1 in 200 UK deaths. This mortality is greater than colon, breast and prostate cancer combined. Glucocorticoids are used to treat a range of inflammatory conditions (e.g. asthma, eczem...