Searchable abstracts of presentations at key conferences in endocrinology

ea0067o20 | Oral Presentations | EYES2019

Phenotype of patients carrying the c.709(-7-2)del PRKAR1A mutation in a large cohort of 40 patients

Abderrahmane Fatimetou , Raverot Gerald , Lefebvre Herve , Cardot-Bauters Catherine , Vantyghem Marie-Christine , Bertherat Jerome , Espiard Stephanie

Objective: To describe the Carney Complex (CNC) manifestations presented by patients harboring the PRKAR1A mutation c.709(-7-2)del (one of the three hotspots) in a large cohort of patients.Methods: Multicenter retrospective study. Age at the diagnosis or at the screening of the different CNC manifestations is described by mean ± standard deviation.Results: Forty patients [12 index cases, 27 females, 46±15 years o...

ea0063oc6.4 | Obesity | ECE2019

Fat mass impact of sirolimus after clinical islet transplantation, a case control study

Jannin Arnaud , Espiard Stephanie , Hoth-Guechot Helene , Kerr-Conte Julie , Pattou Francois , Vantyghem Marie-Christine

Introduction: Sirolimus, a mTOR (mechanistic Target of Rapamycin) inhibitor, is well known for its impact on glucides and lipids metabolism. These effects vary according to factors such as dose and treatment duration, species, cell types and environmental factors. In vitro and in vivo, sirolimus inhibits adipogenesis by decreasing adipocytes number and size, as well as pre-adipocytes differentiation, leading to subcutaneous and visceral fat mass decrease in m...

ea0037ep1216 | Clinical Cases–Pituitary/Adrenal | ECE2015

ARMC5 mutation in a family with Cushing syndrome due to bilateral macronodular adrenal hyperplasia

Rego Teresa , Fonseca Fernando , Agapito Ana , Espiard Stephanie , Perlemoine Karine , Bertherat Jerome

Introduction: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare aetiology of Cushing syndrome. Familial clustering suggests a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat containing 5 (ARMC5) gene.Clinical case: A 70 years old female admitted due to femoral neck fracture in May 2014, presented central obesity, rubeosis and hypertension. Laboratory work up reveale...

ea0056oc6.3 | Genetic and environmental determinants of obesity and insulin resistance | ECE2018

Visceral fat assessment in lamin A/C mutation carriers: phenotype –genotype correlation

Kwapich Maxime , Espiard Stephanie , Le Mapihan Kristell , Vigouroux Corinne , Vantyghem Marie-Christine

Background: Lamin A/C mutations show heterogeneous phenotypes expanding from cardiopathies to lipodystrophies. R482-LMNA gene mutation is the hot-spot for familial partial lipodystrophic syndromes (FPLD2) and is characterized by an increase of intra-abdominal (visceral) fat. In contrast, the visceral fat phenotype of non-R482-LMNA mutated patients has not been well studied.Objectives: To compare the fat amount and visceral repartition o...

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...

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...

ea0049ep1439 | Thyroid (non-cancer) | ECE2017

A higher frequency of papillary thyroid carcinoma in myotonic dystrophy

Ben Hamou Adrien , Dhaenens Claire Marie , Espiard Stephanie , Benomar Kanza , Tiffreau Vincent , Caiazzo Robert , Aubert Sebastien , Vantyghem Marie Christine

Background and purpose: Type 1 myotonic dystrophy (MD), associates neuromuscular, cardiac, respiratory and endocrine disorders. The aim of this study was to determine the prevalence of thyroid disorders and of any causal factors.Methods: A retrospective single centre study was conducted, between 2000 and 2016, in 127 MD patients, diagnosed by familial genetic screening after informed consent. Clinical examination, TSH assay, 120-min glucose and insulin l...

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 ...

ea0063p808 | Thyroid 2 | ECE2019

Clinical presentation of hypothyroidism caused by TSH-receptor antibody

Jannin Arnaud , Peltier Lucas , D'Herbomez Michele , Defrance Frederique , Marcelli Sophie , Ben Hamou Adrien , Humbert Linda , Wemeau Jean-Louis , Vantyghem Marie-christine , Espiard Stephanie

Introduction: Anti-thyrotropin receptor antibodies (TSHR-Abs) stimulating the thyroid (TSAb) are responsible for Graves’ disease. In some patients, the TSHR-Abs can block thyrotropin action (TBAb) and cause hypothyroidism, the switch between stimulating and blocking activity in Graves’ disease being well. This reports aims to describe clinical presentation of patients affected directly by hypothyroidism.Material and methods: Retrospective clini...