Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0016oc4.1 | Bone and adrenal | ECE2008

Inactivation of the Carney complex (CNC) gene 1 (PKA regulatory subunit 1A, PRKAR1A) by interference RNA alters multiple signaling pathways and decreases apoptosis

Ragazzon Bruno , Cazabat Laure , Rizk-Rabin Marthe , Perlemoine Karine , Martinez Antoine , Bertherat Jerome

The cAMP signaling pathway plays an important role in cell proliferation and differentiation, and can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Inactivating mutations of PRKAR1A are observed in CNC (a dominant autosomal hereditary disease responsible for primary pigmented nodular adrenocortical disease, cardiac myxoma and lentiginosis). Most PRKAR1A mutations lead to mRNA unstability and protein degrad...

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...

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...

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 ...

ea0081p543 | Adrenal and Cardiovascular Endocrinology | ECE2022

Whole blood transcriptomic profile of Cushing’s syndrome

Armignacco Roberta , Daniel De Murat , Jouinot Anne , Bouys Lucas , Perlemoine Karine , Letourneur Franck , Adoux Lucie , Zennaro Maria-Christina , Bertherat Jerome , Assie Guillaume

Background: Cushing’s syndrome, caused by an excess of circulating glucocorticoids, is associated with high morbidity and presents high inter-individual variability. The earlier the diagnosis, the better the treatment effectiveness and the prognosis. Hormone assays, routinely used, contribute to identify Cushing’s syndrome. However, no biomarker is currently available to directly quantify the biological action of glucocorticoids. Blood samples represent an easily obt...

ea0063oc13.5 | Anterior and Posterior pituitary 2 | ECE2019

Pan-genomic classification of pituitary adenomas

Neou Mario , Villa Chiara , Armignacco Roberta , Jouinot Anne , Septier Amandine , Raffin-Sanson Marie-Laure , Perlemoine Karine , Bernier Michele , Baussart Bertrand , Bertherat Jerome , Gaillard Stephan , Assie Guillaume

Pituitary adenomas, now called pituitary neuroendocrine tumors (PitNETs), vary in histological type, secretion, invasion and growth speed. A World Health Organization (WHO) histo-prognostic classification was released in 2017. Pituitary tumorigenesis is largely unexplained. Rare germline mutations (MENIN, AIP), and common somatic mutations in somatotroph (GNAS) and corticotroph (USP8) are reported. Recently, genomic analyses have been report...

ea0063gp243 | Anterior and Posterior Pituitary | ECE2019

Histological classification of pituitary neuroendocrine tumors: genomic insights on cell lineage

Villa Chiara , Neou Mario , Armignacco Roberta , Jouinot Anne , Septier Amandine , Perlemoine Karine , Bernier Michele , Laure Raffin-Sanson Marie , Baussart Bertrand , Bertherat Jerome , Gaillard Stephan , Assie Guillaume

The 2017 World Health Organization (WHO) classification of pituitary adenomas is based on cell lineage and transcription factors (TFs). Pituitary progenitors expressing Pit-1 are driven towards the somato-lacto-thyrotroph differentiation, T-Pit towards corticotroph, and SF-1 towards gonadotroph. We recently generated a multi-genomic classification of pituitary neuroendocrine tumors (PitNETs) (abstract submitted to ECE2019 by Neou M.). Transcriptome classification identified si...

ea0063p452 | Adrenal and Neuroendocrine Tumours 2 | ECE2019

Identification of a molecular signature of hypercortisolism by whole blood methylome analysis

Armignacco Roberta , Septier Amandine , Gaspar Cassandra , Jouinot Anne , Neou Mario , Perlemoine Karine , Zennaro Maria Christina , Reincke Martin , Bertherat Jerome , Beuschlein Felix , Assie Guillaume

The prolonged exposure to an excess of circulating cortisol (Cushing’s syndrome) causes various complications. An accurate and early diagnosis is critical for effective surgical management and optimal prognosis. However, the current diagnostic approach based on hormonal assays can be complex and requires multiple tests. The identification of novel, specific and easily measurable biomarkers of hypercortisolism may help to improve the diagnosis and to evaluate the complicat...

ea0016p311 | Endocrine tumours | ECE2008

Parathyroid-hormone related- Peptide and PTHrP receptor type 1 are expressed in human adrenocortical carcinoma and regulate cell proliferation and apoptosis in H295R an adrenocortical-derived cell line

Rizk-Rabin Marthe , Assie Guillaume , Fernande Fernande , Perlemoine Karine , Hamzaoui Hinda , Tissier Frederique , Lieberherr Michele , Bertagna Xavier , Bertherat Jeroome , Bouizar Zhor

Adrenocortical tumor (ACT) is a rare, heterogeneous malignancy whose pathogenesis is unclear. The oncoprotein PTHrP, found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the receptor PTH-R1. Little is known about the role of PTHrP in ACT. We monitored the synthesis of PTHrP and PTH-R1 in a series of 25 ACT: 12 adrenocortical carcinoma (ACC), 13 adrenocortical adenoma (ACA), and investigated the effects of PTHrP (1–34) on H295R c...