Searchable abstracts of presentations at key conferences in endocrinology


Double somatic mutations of CTNNB1 and GNA11 in aldosterone producing adenomas (APAs) presenting in puberty, pregnancy or menopause

Zhou Junhua , Storr Helen , Cottrell Emily , Cabrera Claudia , Argentesi Giulia , Wu Xilin , Goodchild Emily , Azizan Elena , Brown Morris J

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...

ea0081oc13.1 | Oral Communications 13: Adrenal and Cardiovascular Endocrinology 2 | ECE2022

Development of [18F]AldoView as the first highly selective aldosterone synthase PET tracer for imaging of patients with primary hyperaldosteronism

Sander Kerstin , Kurzawinski Tom , Gendron Thibault , Cybulska Klaudia , Sirindil Fatih , Zhou Junhua , Kalber Tammy , Lythgoe Mark , Brown Morris , Williams Bryan , Arstad Erik

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...

ea0065oc5.5 | Adrenal and Cardiovascular | SFEBES2019

Somatic transmembrane domain mutations of a cell adhesion molecule, CADM1, cause primary aldosteronism by preventing gap junction communication between adrenocortical cells

Wu Xilin , Garg Sumedha , Cabrera Claudia , Azizan Elena , Zhou Junhua , Mein Chaz , Takaoka Yutaka , Wozniak Eva , Zhao Wanfeng , Marker Alison , Buss Folma , Murakami Masanori , Beuschlein Felix , Reincke Martin , Ito Akihiko , Brown Morris

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...

ea0077oc4.2 | Adrenal and Cardiovascular | SFEBES2021

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Argentesi Giulia , Azizan Elena , Zhou Junhua , Cabrera Claudia , O’Toole Sam , Wu Xilin , Goodchild Emily , Cottrell Emily , Marker Alison , Senanayake Russell , Garg Sumedha , Jordan Suzanne , Berney Dan , Gluck Anna , Lines Kate , Thakker Rajesh V , Tuthill Antoinette , Joyce Caroline , Karet Frankl Fiona , Metherell Lou , Teo Ada , Gurnell Mark , Parvanta Laila , Drake William , Wozniak Eva , Mein Chaz , Kinsler Veronika , Storr Helen , Brown Morris

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...