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...

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)...

ea0029oc1.2 | Pituitary Clinical I | ICEECE2012

Patients with Cushing’s disease achieve normal urinary cortisol with LCI699, a potent 11β-hydroxylase inhibitor: preliminary results from a multicenter, proof-of-concept study

Bertagna X. , Pivonello R. , Fleseriu M. , Zhang Y. , Robinson P. , Taylor A. , Watson C. , Maldonado M. , Hamrahian A. , Boscaro M. , Biller B.

Introduction: The clinical features and complications of Cushing’s syndrome result from chronic excess of circulating cortisol, typically quantified by 24-h urinary free cortisol (UFC). LCI699 is a potent inhibitor of 11β-hydroxylase. Since 11β-hydroxylase catalyzes the final step of cortisol synthesis, LCI699 is a potential new treatment for all forms of Cushing’s syndrome.Methods: Adult patients with mild-to-severe Cushing’s di...

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...

ea0026oc1.4 | Thyroid/Adrenal | ECE2011

Results of 1,Ortho-1,para′-dichloro-diphenyl-dichloroethane (O,p′DDD) treatment in 76 patients with Cushing's disease

Baudry C , Coste J , Khalil R Bou , Guignat L , Abbas H , Guibourdenche J , Silvera S , Bertagna X , Bertherat J

Introduction: Alternative to transsphenoidal pituitary surgery (TSS) may be required in Cushing’s disease (CD), as first or second line treatment. 1,ortho-1,para′-dichloro-diphenyl-dichloroethane (o,p′DDD) has a potent anticortisolic action. Its place in CD treatment is not well defined. The aim of this study was to further evaluate the efficacy and tolerance of o,p′DDD in CD.Patients and m...

ea0011p489 | Endocrine tumours and neoplasia | ECE2006

Evaluation of a standardized protocol for the collection and storage of adrenal tumor samples – preparation for an European adrenal tumor bank (ENS@T)

Johnsen I , Hahner S , Fassnacht M , Bertherat J , Bertagna X , Plouin PF , Reincke M , Allolio B , Beuschlein F

Tissue samples from adrenal tumors provide the basis for standard diagnostic procedures such as pathological examination. In addition, these tumor samples have been an invaluable source for the discovery of novel molecular pathways involved in adrenal tumorigenesis. Information on the molecular phenotype are based on DNA mutation analysis and epigenetic changes, RNA and protein expression pattern and sub-cellular localization as well as post transcriptional protein modificatio...

ea0029oc13.4 | Adrenal Basic | ICEECE2012

A genome-wide methylation study of adrenocortical tumors shows specific alterations linked to gene expression, revealing new aspects of the molecular classification of adrenal carcinomas

Assie G. , Barreau O. , Wilmot-Roussel H. , Ragazzon B. , Baudry C. , Perlemoine K. , Rene-Corail F. , Dousset B. , Bertagna X. , Tissier F. , De Reynies A. , Bertherat J.

Introduction: DNA methylation is a mechanism for gene expression dysregulation in cancer. Little is known about methylation in adrenocortical tumors (ACT). Previous transcriptome studies proposed an original classification of ACT, first discriminating carcinomas from adenomas, then separating the carcinomas in two groups with different prognosis (C1A and C1B), the poor outcome group (C1A) being divided in three subgroups: p53 inactivation sub-group (C1Ap53), β-catenin act...

ea0019oc14 | Neuroendocrine and Steroids | SFEBES2009

Urinary steroid profiling as a biomarker tool for the detection of adrenal malignancy: results of the EURINE ACC Study

Arlt W , Hahner S , Libe R , Hughes BA , Biehl M , Stiekema H , Schneider P , Smith DJ , Shackleton CHL , Opocher G , Bertherat J , Allolio B , Mannelli M , Mantero F , Fassnacht M , Bertagna X , Stewart PM

Adrenal tumours have an incidence of 2–3% in the general population. Adrenocortical carcinoma (ACC), a highly malignant tumor with a poor prognosis, has an annual incidence of two per million but representation in pre-selected patient cohorts with adrenal masses undergoing surgery is up to 12%. Differentiating adrenocortical adenomas (ACA) from ACC represents a continuous challenge, with unfavourable sensitivities and specificities provided by tumour size, imaging criteri...

ea0029oc7.1 | Adrenal Clinical | ICEECE2012

Progression-free survival without treatment of malignant pheochromocytoma and paraganglioma at one year

Hescot S. , Leboulleux S. , Amar L. , Borget I. , Vezzosi D. , Libe R. , Niccoli P. , Borson-Chazot F. , Do Cao C. , Tabarin A. , de la Fouchardiere C. , Raingeard I. , Chougnet C. , Gimenez-Roqueplo A. , Young J. , Bertherat J. , Wemeau J. , Bertagna X. , Schlumberger M. , Plouin P. , Baudin E.

Pheochromocytoma and paraganglioma are defined as malignant by the occurence of metastasis in extra paraganglionic sites. The natural evolution of these tumors remains unknown.The aim of our retrospective study was to define the progression-free survival (PFS) of untreated Malignant Pheochromocytoma and Paraganglioma (MPP) at 12 months (12 m-PFS) and to look for prognostic markers of 12 m-PFS. We analyzed clinical parameters of patients followed within 8...

ea0029p782 | Endocrine tumours and neoplasia | ICEECE2012

Urinary steroid profiling demonstrates induction of CYP3A4 and inhibition of 5alpha-reductase by mitotane treatment for adrenocortical carcinoma

Taylor A. , Chortis V. , Schneider P. , Tomlinson J. , Hughes B. , Smith D. , Libe R. , Allolio B. , Bertagna X. , Bertherat J. , Beuschlein F. , Fassnacht M. , Mannelli M. , Mantero F. , Opocher G. , Porfiri E. , Quinkler M. , Terzolo M. , Shackelton C. , Stewart P. , Hanher S. , Arlt W.

Mitotane (o,p’DDD) is commonly used for the treatment of adrenocortical carcinoma (ACC), both for advanced disease and in the adjuvant setting. Mitotane induces adrenal insufficiency but specific effects on steroidogenic enzymes are unknown.We investigated 24-h urinary steroid metabolite excretion in ACC patients on adjuvant mitotane (AD) or mitotane for metastatic disease (MET). We compared samples collected before mitotane treatment (BEFORE; MET <...