Searchable abstracts of presentations at key conferences in endocrinology

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 ...

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 ...

ea0073pep8.5 | Presented ePosters 8: Pituitary and Neuroendocrinology | ECE2021

Osilodrostat provides sustained control of urinary free cortisol in patients with Cushing’s disease: final results from a prospective, open-label study (LINC 2)

Fleseriu Maria , Biller Beverly , Bertherat Jerome , Young Jacques , Arnaldi Giorgio , O’Connell Paul , Izquierdo Miguel , Pedroncelli Alberto , Pivonello Rosario

IntroductionThe oral 11β-hydroxylase inhibitor, osilodrostat, normalized mean urinary free cortisol (mUFC) in 79% (15/19) of patients with Cushing’s disease at the end of the 22-week core LINC 2 study. Long-term efficacy and safety data following an optional extension phase are reported here.MethodsPatients with clinical benefit at week 22 could continue receiving osilodrostat during the extension; ...

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...

ea0090oc3.5 | Oral Communications 3: Pituitary and Neuroendocrinology 1 | ECE2023

Interest of serum and salivary cortisol diurnal cycle in the positive diagnostic of Cushing syndrome and in the differential diagnosis of pseudo-Cushing syndrome

Fideline Bonnet , Poirier Jonathan , El Khoury Ralph , Laguillier-Morizot Christelle , Leguy Marie-Clemence , Thomeret Louis , Bouys Lucas , Guignat Laurence , Assie Guillaume , Groussin Lionel , Guibourdenche Jean , Bertherat Jerome

Introduction: Biological diagnosis of Cushing syndrome relies on three parameters: 24 hours-free urinary cortisol; serum cortisol after 1 mg dexamethasone suppression test; late-night serum or salivary cortisol. These tests allow the diagnosis of cortisol excess but do not help in etiological diagnosis, particularly in the distinction between pseudo-Cushing and ACTH-dependent Cushing syndrome, which is often challenging. The aim of this study was to evaluate the performances o...

ea0090oc11.4 | Oral Communications 11: Late Breaking | ECE2023

Persistence of mild hypercortisolism in patients with Cushing’s disease treated with cortisol-lowering drugs : the Haircush study

Manon Fafin , Mohammedi Kamel , Bertherat Jerome , Raverot Gerald , DRUI Delphine , Yves Reznik , Castinetti Frederic , Chanson Philippe , Corentin Rouvray , Amandine Galioot , Brossaud Julie , Tabarin Antoine

Background: Medical treatment with cortisol-lowering drugs is commonly used following pituitary surgical failure or recurrence of hypercortisolism in patients with Cushing’s disease (CD). Studies using late-night salivary cortisol (LNSF) measurement have shown persistent disruption of the circadian secretion of cortisol despite normalization of UFC in a subset of medically treated CD patients. Study aim Our objective was to assess the long-term cortisol exposure in CD pat...

ea0090p673 | Pituitary and Neuroendocrinology | ECE2023

Pooled analysis of osilodrostat dosing across LINC 2, LINC 3 and LINC 4 in Cushing’s disease

Fleseriu Maria , Pivonello Rosario , Lacroix Andre , Biller Beverly M.K. , Feelders Richard , Gadelha Monica , Bertherat Jerome , Belaya Zhanna , Piacentini Andrea , Pedroncelli Alberto , Newell-Price John

Introduction: Phase II (LINC2, NCT01331239) and Phase III (LINC3, NCT02180217; LINC4, NCT02697734) studies showed that osilodrostat, a potent oral 11β-hydroxylase inhibitor, was an effective long-term treatment for Cushing’s disease patients. In this LINC programme pooled analysis, we examined how dose uptitration and adjustments during long-term maintenance can provide rapid, sustained mean urinary free cortisol (mUFC) control, and minimise AEs.<p class="abstext...