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Dive into the research topics where Antoine Tabarin is active.

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Featured researches published by Antoine Tabarin.


The New England Journal of Medicine | 2012

Combination chemotherapy in advanced adrenocortical carcinoma

Martin Fassnacht; Massimo Terzolo; Bruno Allolio; Eric Baudin; Harm R. Haak; Alfredo Berruti; Staffan Welin; Carmen Schade-Brittinger; André Lacroix; Barbara Jarzab; Halfdan Sorbye; David J. Torpy; Vinzenz Stepan; David E. Schteingart; Wiebke Arlt; Matthias Kroiss; Sophie Leboulleux; Paola Sperone; Anders Sundin; Ilse Hermsen; Stefanie Hahner; Holger S. Willenberg; Antoine Tabarin; Marcus Quinkler; Martin Schlumberger; Franco Mantero; Dirk Weismann; Felix Beuschlein; Hans Gelderblom; Hanneke Wilmink

BACKGROUND Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.).


The Journal of Clinical Endocrinology and Metabolism | 2009

Treatment of Pituitary-Dependent Cushing’s Disease with the Multireceptor Ligand Somatostatin Analog Pasireotide (SOM230): A Multicenter, Phase II Trial

Marco Boscaro; W. H. Ludlam; B. Atkinson; J. E. Glusman; Stephan Petersenn; Martin Reincke; Peter J. Snyder; Antoine Tabarin; Beverly M. K. Biller; James W. Findling; Shlomo Melmed; C. H. Darby; K. Hu; Yibin Wang; Pamela U. Freda; Ashley B. Grossman; Lawrence A. Frohman; Jérôme Bertherat

CONTEXT There is currently no medical therapy for Cushings disease that targets the pituitary adenoma. Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder. OBJECTIVE Our objective was to evaluate the short-term efficacy of the novel multireceptor ligand somatostatin analog pasireotide in patients with de novo, persistent, or recurrent Cushings disease. DESIGN We conducted a phase II, proof-of-concept, open-label, single-arm, 15-d multicenter study. PATIENTS Thirty-nine patients with either de novo Cushings disease who were candidates for pituitary surgery or with persistent or recurrent Cushings disease after surgery without having received prior pituitary irradiation. INTERVENTION Patients self-administered sc pasireotide 600 microg twice daily for 15 d. MAIN OUTCOME MEASURE Normalization of urinary free cortisol (UFC) levels after 15 d treatment was the main outcome measure. RESULTS Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom five (17%) had normal UFC levels (responders), after 15 d of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment. Responders appeared to have higher pasireotide exposure than nonresponders. CONCLUSIONS Pasireotide produced a decrease in UFC levels in 76% of patients with Cushings disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.


European Journal of Endocrinology | 2011

AME Position Statement on Adrenal Incidentaloma.

Massimo Terzolo; Antonio Stigliano; Iacopo Chiodini; Paola Loli; Lino Furlani; Giorgio Arnaldi; Giuseppe Reimondo; Anna Pia; Vincenzo Toscano; Michele Zini; Giorgio Borretta; Enrico Papini; Piernicola Garofalo; Bruno Allolio; Benoit Dupas; Franco Mantero; Antoine Tabarin

OBJECTIVE To assess currently available evidence on adrenal incidentaloma and provide recommendations for clinical practice. DESIGN A panel of experts (appointed by the Italian Association of Clinical Endocrinologists (AME)) appraised the methodological quality of the relevant studies, summarized their results, and discussed the evidence reports to find consensus. RADIOLOGICAL ASSESSMENT Unenhanced computed tomography (CT) is recommended as the initial test with the use of an attenuation value of ≤10 Hounsfield units (HU) to differentiate between adenomas and non-adenomas. For tumors with a higher baseline attenuation value, we suggest considering delayed contrast-enhanced CT studies. Positron emission tomography (PET) or PET/CT should be considered when CT is inconclusive, whereas fine needle aspiration biopsy may be used only in selected cases suspicious of metastases (after biochemical exclusion of pheochromocytoma). HORMONAL ASSESSMENT: Pheochromocytoma and excessive overt cortisol should be ruled out in all patients, whereas primary aldosteronism has to be considered in hypertensive and/or hypokalemic patients. The 1 mg overnight dexamethasone suppression test is the test recommended for screening of subclinical Cushings syndrome (SCS) with a threshold at 138 nmol/l for considering this condition. A value of 50 nmol/l virtually excludes SCS with an area of uncertainty between 50 and 138 nmol/l. MANAGEMENT Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess. Data are insufficient to make firm recommendations for or against surgery in patients with SCS. However, adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.


The Journal of Clinical Endocrinology and Metabolism | 2015

Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline.

Lynnette K. Nieman; Beverly M. K. Biller; James W. Findling; M. Hassan Murad; John Newell-Price; Martin O. Savage; Antoine Tabarin

OBJECTIVE The objective is to formulate clinical practice guidelines for treating Cushings syndrome. PARTICIPANTS Participants include an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. The European Society for Endocrinology co-sponsored the guideline. EVIDENCE The Task Force used the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS The Task Force achieved consensus through one group meeting, several conference calls, and numerous e-mail communications. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS Treatment of Cushings syndrome is essential to reduce mortality and associated comorbidities. Effective treatment includes the normalization of cortisol levels or action. It also includes the normalization of comorbidities via directly treating the cause of Cushings syndrome and by adjunctive treatments (eg, antihypertensives). Surgical resection of the causal lesion(s) is generally the first-line approach. The choice of second-line treatments, including medication, bilateral adrenalectomy, and radiation therapy (for corticotrope tumors), must be individualized to each patient.


Nature Genetics | 2014

Integrated genomic characterization of adrenocortical carcinoma

Guillaume Assié; Eric Letouzé; Martin Fassnacht; Anne Jouinot; Windy Luscap; Olivia Barreau; Hanin Omeiri; S. Rodriguez; Karine Perlemoine; F. René-Corail; Nabila Elarouci; Silviu Sbiera; Matthias Kroiss; Bruno Allolio; Jens Waldmann; Marcus Quinkler; Massimo Mannelli; Franco Mantero; Thomas G. Papathomas; Ronald R. de Krijger; Antoine Tabarin; V. Kerlan; Eric Baudin; Frédérique Tissier; Bertrand Dousset; Lionel Groussin; Laurence Amar; Eric Clauser; Xavier Bertagna; Bruno Ragazzon

Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the β-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.


The Journal of Clinical Endocrinology and Metabolism | 2010

Clinical characteristics and therapeutic responses in patients with Germ-line AIP mutations and pituitary adenomas : An international collaborative study

Adrian Daly; Maria A. Tichomirowa; Patrick Petrossians; Elina Heliövaara; Marie Lise Jaffrain-Rea; Anne Barlier; Luciana A. Naves; Tapani Ebeling; Auli Karhu; Antti Raappana; Laure Cazabat; Ernesto De Menis; Carmen Fajardo Montañana; Gérald Raverot; Robert J. Weil; Timo Sane; Dominique Maiter; Sebastian Neggers; Maria Yaneva; Antoine Tabarin; Elisa Verrua; Eija Eloranta; Arnaud Murat; Outi Vierimaa; Pasi I. Salmela; Philippe Emy; Rodrigo A. Toledo; María Isabel Sabaté; Chiara Villa; Marc Popelier

CONTEXT AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN This study was an international, multicenter, retrospective case collection/database analysis. SETTING The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.


Journal of Clinical Investigation | 2000

A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism

Antoine Tabarin; John C. Achermann; Dominique Recan; Véronique Bex; Xavier Bertagna; Sophie Christin-Maitre; Masafumi Ito; J. Larry Jameson; Philippe Bouchard

Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). In affected boys, primary adrenal insufficiency occurs soon after birth or during early childhood; HHG is recognized at the expected time of puberty. In this report, we describe the novel phenotype of a man who presented with apparently isolated adrenal insufficiency at 28 years of age. Examination revealed partial pubertal development and undiagnosed incomplete HHG. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. Genomic analysis revealed a novel missense mutation, I439S, in DAX1. The mutant DAX-1 protein was studied for its ability to function as a transcriptional repressor of target genes. Consistent with the patients mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX-1 when compared with mutations associated with classic AHC. This unique case extends the clinical spectrum of AHC to include delayed-onset primary adrenal insufficiency in adulthood and milder forms of HHG. Furthermore, in accordance with findings in Ahch (Dax1) knockout mice, the clinical features in this patient suggest that DAX-1 function is required for spermatogenesis in humans, independent of its known effects on gonadotropin production.


European Journal of Endocrinology | 2011

The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics

Elena Valassi; Alicia Santos; Maria Yaneva; Miklós Tóth; Christian J. Strasburger; Philippe Chanson; John Wass; Olivier Chabre; Marija Pfeifer; Richard A. Feelders; S. Tsagarakis; Peter J Trainer; Holger Franz; Kathrin Zopf; Sabina Zacharieva; Steven W. J. Lamberts; Antoine Tabarin; Susan M. Webb

OBJECTIVE The European Registry on Cushings syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushings syndrome (CS). DESIGN AND METHODS Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%). RESULTS Proportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups. CONCLUSIONS The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.


European Journal of Endocrinology | 2008

Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire

Susan M. Webb; Xavier Badia; María José Barahona; Annamaria Colao; Christian J. Strasburger; Antoine Tabarin; M. O. van Aken; Rosario Pivonello; G. K. Stalla; S. W. J. Lamberts; Joan Glusman

UNLABELLED Chronic exposure to hypercortisolism has significant impact on patients health and health-related quality of life (HRQoL), as demonstrated with generic questionnaires. We have developed a disease-generated questionnaire to evaluate HRQoL in patients with Cushings syndrome (CS; CushingQoL). OBJECTIVE Validate the CushingQoL questionnaire in patients with CS in clinical practice conditions. DESIGN Observational, international, cross-sectional study. METHODS A total of 125 patients were recruited by 14 investigators from Spain, France, Germany, The Netherlands, and Italy over a 2-month period. Clinical and hormonal data were collected and correlated with results of the generic short form 36 (SF-36) questionnaire, a question on self-perceived general health status and the CushingQoL score. RESULTS A total of 107 patients were pituitary-dependent and 18 adrenal-dependent CS; 104 (83%) were females, mean age 45 years (range 20-73 years); 39 (31%) were currently hypercortisolemic; and 47 (38%) adrenal insufficient. In clinical practice, CushingQoL was feasible (117; 94% of patients fully responded to the questionnaire in a mean time of 4 min), reliable (Crohnbachs alpha=0.87), and valid (factorial analysis demonstrated unidimensionality and Rasch analysis lead to a final version with 12 items). A significant (P<0.001) correlation was observed between CushingQoL score and patients self-perceived general health status and dimensions of SF-36 (Pearsons correlation coefficient > or =0.597). Patients with current hypercortisolism scored worse (lower) than those without (44+/-22 vs 56+/-21, P=0.004). Linear regression analysis identified female gender and hypercortisolism as significant predictors for worse QoL. CONCLUSION CushingQoL is useful to evaluate HRQoL in patients with CS and correlates with clinical parameters.


European Journal of Endocrinology | 2011

High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas

Maria A. Tichomirowa; Anne Barlier; Adrian Daly; Marie Lise Jaffrain-Rea; Cristina Ronchi; Maria Yaneva; Jonathan D. Urban; Patrick Petrossians; Atanaska Elenkova; Antoine Tabarin; R. Desailloud; Dominique Maiter; T. H. Schurmeyer; Renato Cozzi; Marily Theodoropoulou; Caroline Sievers; Ignacio Bernabeu; Luciana A. Naves; Olivier Chabre; Carmen Fajardo Montañana; Vaclav Hana; Georges Halaby; B. Delemer; José Ignacio Labarta Aizpún; E. Sonnet; Ángel Ferrández Longás; Marie Thérèse Hagelstein; Philippe Caron; Günter K. Stalla; Vincent Bours

BACKGROUND Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

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Olivier Chabre

Centre Hospitalier Universitaire de Grenoble

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Philippe Caron

Paul Sabatier University

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Eric Baudin

Institut Gustave Roussy

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