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...

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...

ea0063gp13 | Adrenal and Neuroendocrine - Tumour | ECE2019

KCTD20, a new gene in cortisol-secreting adrenocortical tumors related to inactivating mutations of the Carney Complex gene (PRKAR1A)

Briere Mathilde , Ragazzon Bruno , Yu Bo , Bouchekioua Abdelghani , Bertherat Jerome , Rizk-Rabin Marthe

Introduction: Adrenal Cushing due to bilateral multiple adrenal tumors known as Primary Pigmented Nodular Adrenocortical Disease (PPNAD) can be observed in the multiple neoplasia syndrome Carney Complex or as an isolated disease. In both situations germline inactivating mutations of PRKAR1A (regulatory subunit R1A of PKA) can be observed. The loss of PKA R1A results in an increased PKA activity. Comparison of the transcriptome of PPNAD and stably transfected H295R adr...

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...

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...