Searchable abstracts of presentations at key conferences in endocrinology

ea0016p656 | Signal transduction | ECE2008

Consequences of PRKAR1A (Carney complex gene) inactivation on cellular and subcellular PKA activity monitored by FRET-based reporters

Cazabat Laure , Ragazzon Bruno , Varin Audrey , Perlemoine Karine , Zhang Jin , Bertherat Jerome , Vandecasteele Gregoire

cAMP/PKA pathway activation is frequently involved in endocrine tumors with overactivity. The Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome which associates cardiac myxomas, spotty skin pigmentation and endocrine overactivity. Mutations in the PRKAR1A gene located at 17q22-24 and encoding for the R1A regulatory subunit of protein kinase A have been found in about 60% of CNC. These mutations are heterozygous germline mutations leading to ab...

ea0056gp38 | Adrenal cortex | ECE2018

Identification of a new target of PRKAR1A (Carney complex gene): KCTD20 (potassium channel tetramerization domain containing 20) and study of its role in adrenal Cushing

Ragazzonn Bruno , Yu Bo , Bouchekioua Abdelghani , Bertherat Jerome , Rizk-Rabin Marthe

Introduction: The inactivating mutations of the Carney complex gene PRKAR1A (regulatory subunit RIA of PKA) cause bilateral adrenocortical tumors (PPNAD: Primary Pigmented Nodular Adrenocorticel disease) over-secreting cortisol. This leads to stimulation of PKA activity, however the mechanisms of adrenal tumorigenesis and cortisol dysregulation are not fully understood. In order to identify target genes of PRKAR1A inactivation in adrenal cortex we undertook a comparat...

ea0056gp119 | Endocrine Case Reports | ECE2018

Non-syndromic multiple insulinomas with atypical clinico-biological presentation in two adult patients: a specific entity?

Bonnet-Serrano Fideline , Lethielleux Gaelle , Gaujoux Sebastien , North Marie-Odile , Terris Benoit , Guibourdenche Jean , Bertherat Jerome

Introduction: Insulinoma is the most frequent functional endocrine tumor of the pancreas but remains rare with an incidence of less than 5 cases by million and by year. It is often sporadic but can occur in the context of MEN1 in about 5% of cases, being then readily multiple. Clinically, it is typically responsible for fasting hypoglycemic episodes. Only one case of multiple insulinomas, with no obvious argument for MEN1 context, has previously been reported (Babic an al., <e...

ea0073pep1.6 | Presented ePosters 1: Adrenal and Cardiovascular Endocrinology | ECE2021

ARMC5 modifies cell redox state to regulate steroidogenesis and lipid metabolism in the adrenal cortex

Isadora Pontes Cavalcante , Rizk-Rabin Marthe , Perlemoine Karine , Ribes Christopher , Jerome Bertherat , Ragazzon Bruno

BackgroundARMC5 is a putative tumor suppressor gene that is frequently mutated in primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing’s syndrome. The function of ARMC5 is poorly known, aside the fact that it regulates cell apoptosis and adrenal steroidogenesis in by mechanisms still unknown. Tumor suppressor genes play an important role in oxidative stress.MethodsIn this s...

ea0081p13 | Adrenal and Cardiovascular Endocrinology | ECE2022

ARMC5 as a possible regulator of acetylation in the adrenal cortex in partnership with SIRT1

Berthon Annabel , Faucz Fabio , Feldman Benjamin , Drougat Ludivine , espiard Stephanie , Pontes Cavalcante Isadora , Ragazzon Bruno , Bertherat Jerome , Stratakis Constantine

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARM...

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...

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...

ea0049gp28 | Adrenal 3 | ECE2017

A PRKACB somatic mutation in a cortisol producing adenoma: a new example of protein kinase A activation leading to adrenal Cushing syndrome

Espiard Stephanie , Knape Matthias , Bathon Kerstin , Assie Guillaume , Abid Daniel , Faillot Simon , Calebiro Davide , Herberg Friedrich , Stratakis Constantine , Bertherat Jerome

Introduction: Alterations of the cAMP signaling pathway are described in adrenal tumors causing Cushing syndrome, specifically mutations in the gene coding for the protein kinase A (PKA) catalytic subunit alpha (PRAKCA) in cortisol producing adenomas (CPA) with overt Cushing syndrome.Materiel and Methods: Eight CPAs without PRKACA mutations were analyzed by whole exome sequencing. Direct sequencing of PRAKCB encoding for the catalytic subunit beta (C&#94...