Searchable abstracts of presentations at key conferences in endocrinology

ea0065pl8 | Clinical Endocrinology Trust Visiting Professor Lecture | SFEBES2019

Cushing’s syndrome as a model of endocrine tumorigenesis

Bertherat Jerome

Cushing’s syndrome is a fascinating clinical challenge, both for diagnosis and management. Despite being a rare disease, it has many causes consisting of a broad variety of tumors. These tumors can arise from different tissues (i.e. pituitary, adrenal, lung…) varying from small benign and even non detectable tumors, to large aggressive cancers. The secretory spectrum of these tumors is broad qualitatively and quantitatively. It results from the molecular alterations...

ea0040l11 | New insights on adrenocortical tumors OMICs | ESEBEC2016

New insights on adrenocortical tumors OMICs

Bertherat Jerome

There is a variety of adrenocortical tumors that can be responsible for different cortisol excess levels. Genomics allowed recently many progress in this field. Exome sequencing allowed to identify somatic activating mutations of the catalytic subunit of PKA (PRKACA) in cortisol secreting adenomas responsible for overt-Cushing. Combining pangenomic snp analysis and whole genome sequencing led to the identification of inactivating germline mutations of a new tumor supp...

ea0032s17.2 | Medical treatment of endocrine malignancies - an update | ECE2013

Medical treatment of adrenocortical cancer

Bertherat Jerome

Adrenocortical cancer (ACC) is a rare tumor with an overall poor prognosis. However outcome is heterogeneous and the indication and type of medical therapy should be personalized on the basis of tumor stage and prognostication. The initial diagnostic and extension work-up of an ACC is an important step. Most patients with ENSAT stage 1–3 ACC and some stage 4 ACC will be operated and pathological analysis is important for management. The goals of medical treatment are to c...

ea0049gp13 | Adrenal 2 | ECE2017

PRKARIA (Carney complex gene) is a major regulator of the tight link between cell cycle phases and steroidogenesis in the adrenocortical tumor cells H295R

Rizk-Rabin Marthe , Ragazzon Bruno , Bertherat Jerome

The cyclic AMP/PKA signalling cascade is involved in the pathogenesis of cortisol-secreting adrenocortical tumors (ACT). Defects in cell cycle checkpoints play a major role in oncogenesis. The PKA regulatory subunits PRKARIA and PRKARIIb are involved in cell survival and steroidogenesis in the adrenocortical carcinoma H295R cell line. We have previously shown that their inactivation enhances the accumulation of cells in the G2 phase and act...

ea0041oc2.4 | Receptors & Signalling | ECE2016

Link between cell cycle, steroidogenesis and PKA in adrenocortical tumors cells

Rizk-Rabin Marthe , Ragazzon Bruno , Bertherat Jerome

The cyclic AMP/PKA signalling cascade and PKA subunits are involved in the pathogenesis of a subset of cortisol-secreting adrenocortical tumors (ACT). In addition, steroid excess causes morbidity of all types of ACT.The PKA regulatory subunits PRKARIA, PRKARIIb control proliferation/apoptosis in the H295R adrenocortical cell line. Their inactivation enhances the accumulation of cells in the G2 phase, increases steroidogenesis and activa...

ea0022p37 | Adrenal | ECE2010

Inactivation of PRKARIA or PRKAR2B increases cell proliferation and decreases apoptosis, delineating distinct molecular mechanisms in adrenocortical human H295R cell line

Ragazzon Bruno , Bertherat Jerome , Rizk-Rabin Marthe

The cAMP signaling cascade is one of the main pathways involved in the pathogenesis of adrenocortical tumors (ACT). Protein kinase A (PKA) is a key element of this pathway. The R1A and R2B proteins are the most abundant regulatory subunits in endocrine tissues. Inactivating mutations of PRKAR1A are observed in Carney complex and a subset of ACT. We have recently reported that inactivation of PRKAR1A dysregulates cAMP pathway and reduces TGFβ-induced apoptosi...

ea0090p13 | Adrenal and Cardiovascular Endocrinology | ECE2023

Prolonged Adrenocortical Blockade Following Interruption of Osilodrostat in ACTH-dependent Cushing’s syndrome

Poirier Jonathan , Bonnet-Serrano Fideline , Thomeret Louis , Bouys Lucas , Bertherat Jerome

Introduction: Osilodrostat is the newest approved steroidogenic inhibitor drug for the treatment of Cushing’s syndrome (CS). In this presentation, we describe 3 patients who experienced an unexpectedly prolonged adrenal insufficiency following interruption of this treatment.Methods: A monocentric retrospective analysis (October 2019 to January 2023) of ACTH-dependent CS patients controlled with Osilodrostat was performed to identify patients with pr...

ea0090p291 | Adrenal and Cardiovascular Endocrinology | ECE2023

ARMC5 regulates SIRT1 expression in adrenocortical cells

Berthon Annabel , Fabio Faucz , Benjamin Feldman , Ludivine Drougat , Stephanie Espiard , Bertherat Jerome , Stratakis Constantine

Pathogenic ARMC5 variants are the main genetic cause of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) explaining roughly 20% of index cases. These variants found both at germline and somatic level are mostly frameshift and nonsense leading to a loss of its function. ARMC5 acts then, as a tumor suppressor gene but little was initially known on its function. Using an RNAseq analysis on transient zebrafish models of Armc5 up- and d...

ea0090ep69 | Adrenal and Cardiovascular Endocrinology | ECE2023

Effects of Osilodrostat and Metyrapone on steroidogenesis in adrenocortical H295R tumor cells in vitro

Thomeret Louis , Berthon Annabel , Perlemoine Karine , Poirier Jonathan , Blanchet Benoit , Puszkiel Alicja , Bertherat Jerome , Fideline Bonnet

Introduction: Osilodrostat and Metyrapone are two CYP11B1 inhibitors used for the treatment of patients with Cushing syndrome. Despite their common suspected mechanism of action, the comparison of serum steroid profiles determined in HPLC-MS/MS in patients treated by either Osilodrostat or Metyrapone for an ACTH-dependent Cushing syndrome identified higher levels of 11-deoxycortisol and androgens in patients treated by Metyrapone than in those treated by Osilodrostat (F. B...

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...