Searchable abstracts of presentations at key conferences in endocrinology

ea0081p270 | Adrenal and Cardiovascular Endocrinology | ECE2022

Proposition of the first histopathological classification of primary bilateral macronodular adrenal hyperplasia (pbmah) and its correlation with armc5 and kdm1a status

Violon Florian , Bouys Lucas , Vaczlavik Anna , Gaetan Giannone , Berthon Annabel , Ragazzon Bruno , Terris Benoit , Sibony Mathilde , Bertherat Jerome

Introduction: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome. It is characterized by the development of supracentimetric nodules resulting in increased adrenal volume and weight. Its presentation is clinically, radiologically and biologically heterogeneous. Morphological descriptions of PBMAH are rare. Although the initial description highlights that multinodular hyperplastic adrenal glands are made of a majority...

ea0090rc5.3 | Rapid Communications 5: Adrenal and Cardiovascular Endocrinology 1 | ECE2023

Study of somatic molecular heterogeneity in bilateral macronodular adrenocortical disease (BMAD) by NGS panel in a cohort of 26 patients

Violon Florian , Bouys Lucas , Gaetan Giannone , Vaduva Patricia , Perlemoine Karine , Berthon Annabel , Ragazzon Bruno , Sibony Mathilde , Bertherat Jerome

Introduction: Bilateral macronodular adrenal disease (BMAD) is a genetically heterogeneous disease that can be caused by ARMC5 or KDM1A alterations. Indeed, a germline and somatic event leading to a bi-allelic inactivation of ARMC5 or KDM1A are responsible for 20 and 1% of BMAD cases, respectively. Genetic analysis identified three molecular groups: ARMC5, KDM1A and no genetic cause known to date. Although there is a high h...

ea0090rc6.1 | Rapid Communications 6: Endocrine-related Cancer | ECE2023

Aberrant activation of Wnt/β-Catenin signaling pathway drives the expression of poor prognosis-associated microRNAs in adrenocortical cancer

Cristante Justine , El Sayed Soha Reda , Denis Josiane , Ragazzon Bruno , Constanze Hantel , Chabre Olivier , Guyon Laurent , Cherradi Nadia

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Deregulated microRNA (miRNA) expression has been implicated in ACC aggressiveness. Nevertheless, the mechanisms underlying such deregulations remain unknown. Aberrant Wnt/β-Catenin signaling has been reported in about 40% of ACC and is associated with poor outcome. In the present work, we aimed to investigate the link between constitutive activation of Wnt/β-Catenin pathway and miRNA expressio...

ea0063oc10.4 | Adrenal 2 | ECE2019

Cullin 3 is a partner of armadillo repeat containing 5 (ARMC5), the product of the gene responsible for primary bilateral macronodular adrenal hyperplasia

Cavalcante Isadora , Vaczlavik Anna , Drougat Ludivine , Lotfi Claudimara , Fragoso Maria , Clauser Eric , Rizk-Rabin Marthe , Bertherat Jerome , Ragazzon Bruno

Background: Germline mutations of ARMC5 (Armadillo repeat containing 5 gene) were identified as a frequent cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). ARMC5 is considered as a tumor suppressor gene regulating apoptosis and steroidogenesis by unknown mechanisms. The ARMC5 protein contains a N-terminal domain made of Armadillo (ARM) repeats and a C-terminal ‘Bric-a-Brac, Tramtrack, Broad-complex/Pox virus and Zinc finger (BTB/POZ)&...

ea0063gp102 | Adrenal and Neuroendocrine - Basic | ECE2019

Development of a simple experiment to distinguish ARMC5 missense mutants from rare ARMC5 polymorphisms in PBMAH patients using a quantitative western blot approach

Vaczlavik Anna , Espiard Stephanie , Ribes Christopher , North Marie-Odile , Drougat Ludivine , Ragazzon Bruno , Rizk-Rabin Marthe , Bertherat Jerome

Introduction: Germline inactivating ARMC5 (Armadillo repeat containing 5) mutations are responsible for Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). ARMC5 presents the characteristics of a tumor suppressor gene. Mutations are observed in more than 85% of patients with a clear familial presentation and 20 to 25% of apparently sporadic cases. Genetic alterations are spread all over ARMC5 coding sequence and more than two-third of them ar...

ea0041oc9.1 | Endocrine Tumours | ECE2016

Study of new tumor suppressor gene (ZNRF3) in adrenocortical carcinoma

Hanin Omeiri , Marthe Weinandts , Lucile Lefevre , Ludivine Drougat , Guillaume Assie , Rabin Marthe Rizk , Jerome Bertherat , Bruno Ragazzon

Introduction: Adrenocortical Carcinoma (ACC) is a rare and aggressive tumor with poor prognosis. Up to now, CTNNB1 (βcatenin) and TP53 mutations were the most frequent alterations identified in ACC. By a combination of genomic approaches, we have recently analyzed a cohort of 122 ACC (European Network for the Study of Adrenal Tumors, ENSAT). This work confirmed recurrent alterations in CTNNB1 and TP53 and revealed new genes not previous...

ea0056oc5.5 | Diving deep into adrenal cortex diseases | ECE2018

Cullin 3 is a partner of Armadillo Repeat Containing 5 (ARMC5), the product of the gene responsible for Primary Bilateral Macronodular Adrenal Hyperplasia

Cavalcante Isadora , Clauser Eric , Vaczlavik Anna , Drougat Ludivine , Lotfi Claudimara , Fragoso Maria , Rizk-Rabin Marthe , Bertherat Jerome , Ragazzon Bruno

Background: ARMC5 (armadillo repeat containing 5) has been identified as the gene responsible for PBMAH (Primary Bilateral Macronodular Adrenal Hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5, is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BT...

ea0056gp36 | Adrenal cortex | ECE2018

Identification of new ARMC5 missense mutations in Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) and their functional studies in vitro

Vaczlavik Anna , Espiard Stephanie , North Marie-Odile , Drougat Ludivine , Rizk-Rabin Marthe , Perlemoine Karine , Ragazzon Bruno , Bertherat Jerome

Introduction: ARMC5 germline and somatic inactivating mutations were discovered in patients treated by adrenalectomy for hypercortisolism due to primary bilateral macronodular adrenal hyperplasia (PBMAH). Since then, several ARMC5 germline variants have been described in PBMAH patients. Genetic alterations are spread all over ARMC5 coding sequence and many are missense variants. For them, geneticist conclusions are based on in silico predictions. As ...

ea0037oc1.2 | Adrenal 1 | ECE2015

Functional study of ARMC5 (armadillo repeat containing 5), a new tumour suppressor gene involved in primary bilateral macronodular adrenal hyperplasia

Drougat ludivine , Espiard Stephanie , Doly Stephane , Rodriguez Stephanie , Rizk-Rabin Marthe , Libe Rossella , Assie Guillaume , Marullo Stefano , Ragazzon Bruno , Bertherat Jerome

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) are adrenocortical tumors leading to adrenal Cushing’s syndrome. Recently, our laboratory has identified the first gene predisposing frequently to PBMAH in adults, named ARMC5 (Armadillo Repeat Containing 5)1. The ARMC5-inactivating mutations identified in leucocyte and tumour DNA in PBMAH patients suggest that ARMC5 is a tumour suppressor gene. However, the mechanisms of action of ARMC5 remain unkno...

ea0032p5 | Adrenal cortex | ECE2013

The gene expression profile of cortisol secretion in adrenocortical adenomas

Roussel Hortense Wilmot , Vezzosi Delphine , Rizk-Rabin Marthe , Barreau Olivia , Ragazzon Bruno , Rene-Corail Fernande , de Reynies Aurelien , Bertherat Jerome , Assie Guillaume

The cortisol secretion level of adrenocortical adenomas range from hormonally silent to overt hypercortisolism. The mechanisms leading to the autonomous hypersecretion of cortisol are unknown. The aim was to identify the gene expression alterations associated with the autonomous and excessive cortisol secretion of adrenocortical adenomas.Methods: The transcriptome of 22 unilateral adrenocortical adenomas (5 non-secreting, 6 subclinical cortisol-producing...