Searchable abstracts of presentations at key conferences in endocrinology

ea0063p429 | Adrenal and Neuroendocrine Tumours 2 | ECE2019

Urinary steroid profiling by gas chromatography-mass spectrometry (GC-MS) in Cushing’s syndrome

Bonnet-Serrano Fideline , Vaczlavik Anna , Assie Guillaume , Bertherat Jerome , Menet Marie-Claude

Introduction: Steroid profiling by mass spectrometry approaches consists in the simultaneous measurement of several steroid molecules in a biological sample, allowing an optimal characterization of steroidogenesis alterations, particularly in the context of adrenal tumors. Twenty-four hours urine samples have the advantage of being non-invasive and of giving an integrated view of steroidogenesis. Urinary steroid profiling has thus been shown to be particularly useful in the di...

ea0020s23.2 | Adrenocortical tumours – pathogenesis and management | ECE2009

Aberrant receptors (AR) in adrenal Cushing's syndrome

Libe Rossella , Groussin Lionel , Assie Guillaume , Bertagna Xavier , Chabre Olivier , Lefebvre Herve , Bertherat Jerome

Some elegant clinical observations of dysregulated cortisol-secretion in cases of ACTH-independent macronodular hyperplasia (AIMAH) and more rarely adrenocortical adenomas (ACA) have led to the concept of ‘aberrant’ or ‘illegitimate’ membrane receptors (AR) in adrenal Cushing syndrome. It this situation cortisol secretion is regulated by an extra-cellular ligand that usually does not stimulate cortisol secretion in normal adrenals. This abnormal response mi...

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...

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...

ea0022p47 | Adrenal | ECE2010

Genomic DNA alterations in adrenocortical tumors (ACTs): diagnostic and prognostic value

Assie Guillaume , Barreau Olivia , De Reynies Aurelien , Tissier Fredrique , Groussin Lionel , Bertagna Xavier , Bertherat Jerome , Clauser Eric

The outcome of ACTs can be determined by gene expression level at the RNA level. However RNA handling is challenging. In contrast tumor DNA is robust and therefore easier to use.Aim: To characterize the ACTs DNA alterations; to identify markers with diagnostic and prognostic value using tumor DNA.Methods: The mapping of chromosomal gains and losses of 60 ACTs (39 adenomas (ACAs), 21 carcinomas (ACCs)) was performed with CGH arrays ...

ea0081oc7.4 | Oral Communications 7: Pituitary and Neuroendocrinology 2 | ECE2022

HPLC-MSMS steroidogenic profiles in ACTH-dependent Cushing Syndrome patients treated by osilodrostat or metyrapone suggest differences in the spectrum of steroidogenic enzyme inhibition between the two CYP11B1 inhibitors in clinical care

Fideline Bonnet , Poirier Jonathan , Vaczlavik Anna , Laguillier-Morizot Christelle , Blanchet Benoit , Guignat Laurence , Bessiene Laura , Bricaire Leopoldine , Groussin Lionel , Assie Guillaume , Guibourdenche Jean , Bertherat Jerome

Introduction: Osilodrostat is a new 11 ß-hydroxylase inhibitor with a mode of action analogue to metyrapone. It has become increasingly used in recent years for treatment of Cushing’s Syndrome (CS). However, few in vivo studies are currently available to accurately compare both drugs characteristics. The objective of our study was to compare steroidogenic profiles in patients treated by either Osilodrostat or Metyrapone for ACTH-dependent CS.Me...

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...