Endocrine Abstracts

Background: Hypertension affects more than 30% of the adult population worldwide and is a major cardiovascular risk factor. Identifying secondary causes of hypertension is key to offering targeted treatment and mitigating adverse health outcomes. We tested the performance of urine steroid metabolomics (USM), the computational analysis of 24-hour urine steroid metabolome data by machine learning, for diagnosing endocrine hypertension.<str...

The adrenocorticotrophin hormone (ACTH) receptor, also known as the melanocortin-2-receptor (MC2R), is a key mediator of cortisol synthesis in the adrenal gland. Over 40 loss-of-function MC2R mutations have been described to give rise to familial glucocorticoid deficiency type-1 (FGD1). In contrast, to date only one naturally occurring gain-of-function mutation, F278C, has been identified in a patient with ACTH-independent Cushing’s syndrome. Previous work has demonstrate...

Background: Primary aldosteronism (PA) is the most common potentially curable cause of secondary hypertension and is a risk factor for cardiovascular morbidity and mortality. For patients with unilateral disease adrenalectomy can be curative. However, PA remains substantially underdiagnosed due the complex diagnostic pathway required to identify patients with unilateral disease, and the difficulties in accurate lateralization of the affected adrenal gland. Spe...

The mineralocorticoid receptor (MR) has a modular domain structure containing a C-terminal ligand-binding domain (LBD) that consists of 11 α-helices (designated H1 to H12) organized in an antiparallel helical sandwich. The LBD undergoes a conformational change upon aldosterone binding such that H12 forms a stable interaction with helices 3, 4 and 5 to create an AF-2 domain, a hydrophobic cleft on the surface of the LBD, which serves as a docking platform for transcription...

Hypertension is the most important risk factor in the development of cerebrovascular diseases including vascular cognitive impairment (VCI). Aldosterone is a key regulator of blood pressure, acting via the mineralocorticoid receptor (MR) in the kidney to promote sodium/water reabsorption. Elevated aldosterone, as in primary aldosteronism (PA) is a risk factor for cerebrovascular disease. In addition to its traditional role, the MR is expressed throughout the brain and vasculat...

Glucocorticoids (GCs) protect cardiomyocytes immediately after myocardial infarction (MI), but GCs subsequently regenerated within the heart by 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) are detrimental during infarct repair, with functional outcomes post-MI improved in mice lacking 11βHSD1. Pharmacological 11βHSD1 inhibition (AZD8329 50mg/kg, 11βHSD1i) was compared to standard clinical therapy (SCT) in a translational pig model (female, 11βHSD1...