Searchable abstracts of presentations at key conferences in endocrinology

ea0029p1785 | Thyroid cancer | ICEECE2012

Dual specificity phosphatase 5 (DUSP5), a specific negative feedback regulator of ERK signaling, is controlled by serum response factor (SRF) and Elk-1 transcription factors

Buffet C. , Garcia C. , Catelli M. , Hecale-Perlemoine K. , Bertagna X. , Bertherat J. , Groussin L.

Mitogen-activated protein kinase (MAPK) pathway abnormalities, specifically rearrangements (RET/PTC) or activating mutations (RAS or BRAF), are highly prevalent in papillary thyroid carcinomas (PTCs). Constitutive activation of this signaling cascade causes sustained phosphorylation of extracellular signal-regulated kinase (ERK). DUSP5, which is positively regulated by ERK signaling, acts as a negative regulator of its activity. We have previously shown that DUSP5 is overexpre...

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...

ea0016p60 | Adrenal | ECE2008

Intraadrenal production of ACTH in macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: its role in the physiopathology of hypercortisolism

Louiset Estelle , Duparc Celine , Groussin Lionel , Bertherat Jerome , Bertagna Xavier , Kuhn Jean-Marc , Lefebvre Herve

Illicit expression of membrane receptors for circulating regulatory factors, such as GIP and LH receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of serotonin, arginine vasopressin and ACTH in a subpopulation of steroidogenic cells in two AIMAH tissues. The aim of the present study was: (i) to investigate the presence of ACTH by immunohistochem...

ea0011oc45 | Endocrine genetics | ECE2006

Genotype/phenotype correlation of PRKAR1A mutations in patients with Carney complex (CNC) and/or sporadic primary pigmented nodular adrenocortical disease (PPNAD) from the CNC network

Groussin L , Rene-Corail F , Cazabat L , Jullian E , Clauser E , Bertagna X , Bertherat J

CNC is an autosomal dominant multiple neoplasia syndrome, responsible mainly for cardiac myxomas, pigmented skin lesions and endocrine tumors (acromegaly, thyroid and testicular neoplasms and primary pigmented nodular adrenocortical disease: PPNAD). The PRKAR1A gene was previously found to be mutated in about 41% of CNC kindreds. Most mutations lead to nonsens mediated mRNA decay and preclude expression of the mutant protein. 102 patients (64 with PPNAD and 38 with CNC)...

ea0041gp202 | Thyroid - Translational & Clinical | ECE2016

Does mitotane influence free thyroid hormones levels? A possible explanation in vivo and in vitro

Blanchet Benoit , Clemence Leguy Marie , Le Monnier Aude , Habbas Halim , Claude Menet Marie , Groussin Lionel , Guibourdenche Jean

Mitotane (o.p’DDD, Lysodren) is used to treat adrenortical carcinoma and Cushing syndromes. It is catabolised into o.p’DDA and o.p’DDE. It is lowly protein-bound but its tropism for lipids is high. It has multiple side effects on the digestive gut increasing alkaline phosphatases and cholesterol. Patients treated with mitotane have been described as having decreased FT4 levels without any signs of hypothyroidism. We wanted to know whether this is due to an analy...

ea0029p29 | Adrenal cortex | ICEECE2012

The ACTH-independent macronodular adrenal hyperplasia gene hunt: from candidate genes to a pangenomic strategy

Assie G. , Libe R. , Guimier A. , Espiard S. , Rene-Corail F. , Perlemoine K. , Letourneur F. , Bertagna X. , Groussin L. , Bertherat J.

ACTH-independent macronodular hyperplasia (AIMAH) affects both adrenals, and familial forms are reported, suggesting a genetic origin. Rare mutations have been reported in several genes, including Gs alpha (GNAS), Phosphodiesterase 11A (PDE11A), Fumarate Hydratase (FH), and the Glucocorticoids receptor (GR).Objective: To assess the prevalence known genes mutations, and identify new candidate genes in AIMAH.Design and methods: Germl...

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...

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...

ea0022h1.3 | Oral Communications Highlights 1 | ECE2010

ESE Young Investigator Award

Libe Rossella , Horvath Anelia , Fratticci Amato , Vezzosi Delphine , Coste Joel , Guillaud-Bataille Marine , Groussin Lionel , Clauser Eric , Sanson Marie Laure Raffin , Bertagna Xavier , Stratakis Constantine , Bertherat Jerome

Background: Cushing syndrome due to PPNAD is the main endocrine disorder of CNC, an autosomal dominant multiple neoplasia caused by germline inactivating mutations of the subunit type 1A (PRKAR1A) of the protein kinase A (PKA). In addition, germline inactivating mutations in the gene encoding phosphodiesterase 11A (PDE11A) have been identified in patients with PPNAD.Aim of the study: To investigate the role of PDE11A genetic alterati...