Endocrine Abstracts

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...

Polycystic ovary syndrome (PCOS) affects 10% of women and is associated with an increased risk of type 2 diabetes and fatty liver disease. Androgen excess is an important driver of metabolic risk in PCOS. In adipose tissue from women with PCOS, increased activation of androstenedione (A4) to testosterone (T) by the enzyme AKR1C3 results in systemic lipotoxicity. Recent in-vitro studies also demonstrated that T and 11-ketotestosterone (11KT) activate the androgen recep...

Introduction: The effects of maternal suboptimal gestational thyroid function (SGTF) on age 3 offspring’s cognitive function were investigated in the Controlled Antenatal Thyroid Screening (CATS) randomised trial, comparing SGTF mothers who received (SGTF-T), or didn’t (SGTF-U), levothyroxine during pregnancy. The analysis was repeated at age 9 in the CATS-II follow-up study, also including children of mothers with normal gestational thyroid function (NGTF). Here we ...

Context: Suboptimal thyroid function in pregnancy is associated with adverse obstetric outcomes but it is unclear whether levothyroxine treatment, initiated during pregnancy is beneficial.Design & Participants: Retrospective analysis of the Controlled Antenatal Thyroid Screening (CATS) study with obstetric outcomes obtained through data-linkage in the Secure Anonymised Information Linkage (SAIL) databank. We studied 13,224 pregnant women; 12,608 had ...

Objectives: The Controlled Antenatal Thyroid Screening (CATS) study I was a randomised trial investigating the effects of levothyroxine treatment for suboptimal gestational thyroid function (SGTF), evaluating mothers with normal gestational thyroid function (NGTF), SGTF who received (SGTF-T), or didn’t (SGTF-U), levothyroxine during pregnancy. The present follow-up study (CATS II) reports the long-term effects of SGTF and levothyroxine treatment on anthropometric and card...