Searchable abstracts of presentations at key conferences in endocrinology

ea0029p1410 | Pituitary Clinical | ICEECE2012

Long-term pasireotide use leads to improvements in the biochemical parameters of Cushing’s disease: 24-month results from a randomized phase III study

Schopohl J , Bertherat J , Ludlam W , Maldonado M , Trovato A , Hughes G , Gu F , Salgado L , Pivonello R

Introduction: The large, randomized, phase III study of pasireotide in Cushing’s disease found that pasireotide treatment resulted in rapid and sustained decreases in UFC levels and in significant improvements in signs and symptoms over 12 months of treatment. A 12-month extension of this trial has recently completed, and the results are reported here.Methods: Patients with persistent/recurrent or de novo (if not surgical candidates) Cushing&...

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...

ea0014s8.2 | Advances in adrenal hypersecretory disorders | ECE2007

Carney complex and primary pigmented nodular adrenocortical diasease

Bertherat Jérôme

The Carney complex (CNC) is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. The most common endocrine gland manifestations are acromegaly, thyroid tumors, testicular tumors, and ACTH-independent Cushing’s syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD, a rare cause of Cushing’s syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients ...

ea0029p1 | Adrenal cortex | ICEECE2012

Targeting mutated β-catenin in vitro and in vivo inhibits cell proliferation and stimulates apoptosis: a promising therapeutic target in adrenocortical carcinoma

Ragazzon B. , Gaujoux S. , Hantel C. , Tissier F. , Rizk-Rabin M. , Beuschlein F. , Bertherat J.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic option. Activating β-catenin somatic mutations are observed in ACC and associated with a poor outcome. Activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might be a promising therapeutic target. The H295 cell line derived from an ACC harbors an activating β-catenin mutation. We herein assess the in vi...

ea0029p48 | Adrenal cortex | ICEECE2012

MicroRNA profiling of benign and malignant adrenocortical tumors reveals potential biomarkers of recurrence

Chabre O. , Assie G. , Libe R. , Bertherat J. , Feige J. , Cherradi N.

Objective: To identify miRNAs predictors of poor prognosis in adrenocortical cancer.Methods: Using microarrays, we evaluated the expression of 728 human miRNAs in six adenomas (ACAs) and twelve carcinomas (ACCs). The ACC group was composed of two subgroups A and B consisting of six recurrent (subgroup A) and six non-recurrent tumors (subgroup B). These two distinct subgroups have been characterized recently (de Reynies et al, 2009) on the basis of distin...

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)...

ea0029oc7.2 | Adrenal Clinical | ICEECE2012

Activation of the PKA pathway triggers formation of an illicit serotonergic regulatory loop in primary pigmented nodular adrenal disease (PPNAD) tissues associated with Cushing’s syndrome

Bram Z. , Renouf S. , Duparc C. , Ragazzon B. , Libe R. , Martinez A. , Stratakis C. , Bertherat J. , Louiset E. , Lefebvre H.

In the normal adrenal gland, serotonin (5-HT) stimulates cortisol secretion through activation of 5-HT4 receptors whereas, in some macronodular adrenal hyperplasia tissues, the corticotropic effect of 5-HT is mediated by ectopic 5-HT7 receptors. The aim of the present study was to investigate the role of 5-HT in the control of cortisol secretion in PPNAD tissues from 12 patients by using molecular, immunohistochemical and pharmacological approaches. RT-PCR studies revealed ove...

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...

ea0029p1405 | Pituitary Clinical | ICEECE2012

Long-term use of pasireotide in Cushing’s disease: 24-month safety results from a randomized phase III study

Bertherat J , Ludlam W , Pivonello R , Maldonado M , Trovato A , Hughes G , Gu F , Schopohl J , Salgado L

Introduction: Rapid and sustained decreases in UFC and significant improvements in signs and symptoms were seen in a large, randomized, 12-month phase III study of pasireotide in Cushing’s disease. The safety profile of pasireotide was found to be similar to that of other somatostatin analogues, with the exception of hyperglycemia-related AEs (reported in 72.8% of patients). This abstract reports safety data from a 12-month extension to this phase III trial.<p class="...