Endocrine Abstracts

Background: Inappropriately high aldosterone in patients with primary hyperaldosteronism (PHA) is due to increased aldosterone synthase (CYP11B2) activity. Selective in vivo imaging of overexpressed CYP11B2 in adrenals with positron emission tomography (PET) has not yet been achieved due to close homology of enzymes involved in aldosterone and cortisol (CYP11B1) synthesis.Aim: Synthesize a fluorine-18 labelled highly selective CYP11B2 inhibitor,...

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

Background: Primary aldosteronism (PA) is the leading, potentially reversible, cause of secondary hypertension. For most patients in whom surgery is being considered, adrenal vein sampling (AVS) is recommended to distinguish unilateral and bilateral causes. However, AVS remains technically challenging, and a significant proportion of patients are unable to progress to surgery because AVS is unavailable or unsuccessful. We have explored whether [11C]Metomidate PET/CT...

Adrenal hormones possess both circadian and ultradian rhythms, making interpretation of single time point measurements difficult, particularly in the context of suspected endocrine disease. Attempting to capture either normal or pathological rhythms in detail by traditional measurement of blood is impractical and generally unfeasible. However, minimally invasive microdialysis sampling of free tissue hormones coupled with a portable fraction collector (U-RHYTHM), and a targeted...

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±...

Glucocorticoids synchronise peripheral clocks with the master clock in the suprachiasmatic nucleus of the brain. In humans and mice, abnormal glucocorticoid rhythms induce blood pressure abnormalities accompanied by vascular dysfunction. The mechanisms of this remain unclear. We hypothesise that excessive activation of the glucocorticoid receptor (GR) disrupts circadian clock signalling, altering vascular function and inducing non-dipping blood pressure. We characterise the va...