Endocrine Abstracts

Objective: We reported 3 patients with primary aldosteronism who presented at times of high plasma LH, and had somatic CTNNB1 mutations causing ˜100-fold elevation of LHCGR in their APAs (Teo et al. NEJM 2015). Subsequently we identified 4 further patients, but the association with pregnancy was not found by others. Whole exome sequencing (WES) of an APA diagnosed at onset of puberty suggests an explanation.Method: WES of tumour and blood w...

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, [18...

Background: Primary Aldosteronism (PA) is the commonest curable cause of hypertension. Whole exome sequencing (WES) of an aldosterone producing adenoma from a 46-year-old man with resistant hypertension revealed a novel somatic mutation (Val380Asp) of the single transmembrane domain of Cell Adhesion Molecule-1 (CADM1). A Gly379Asp mutation was identified by WES of a PA patient in Munich. Both patients were cured of hypertension by adrenalectomy.Method: A...

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...