10 results on '"Hélène Du Boullay"'
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2. Efficacy and safety of osilodrostat in paraneoplastic Cushing's syndrome: a real-world multicenter study in France
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Alexandre Dormoy, Magalie Haissaguerre, Géraldine Vitellius, Christine Do Cao, Aurore Geslot, Delphine Drui, Hélène Lasolle, Oceana Vieira-Pinto, Sylvie Salenave, Maud François, Marie Puerto, Hélène Du Boullay, Anne Mayer, Anne Rod, Claire Laurent, Philippe Chanson, Yves Reznik, Frédéric Castinetti, Olivier Chabre, Eric Baudin, Gérald Raverot, Antoine Tabarin, and Jacques Young
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Biochemistry - Abstract
Context Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS). Objective This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS. Methods A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11). Results In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P < .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P < .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P < .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients. Conclusion Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.
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- 2022
3. Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study
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Catherine Cardot-Bauters, François Pattou, Patricia Niccoli, Sophie Deguelte, Philippe Ruszniewski, Maëlle Le Bras, Jean-Christophe Lifante, Fabrice Menegaux, Eric Mirallié, Frederic Sebag, Françoise Borson-Chazot, Gilles Poncet, Philippe Chaffanjon, Eric Baudin, Guillaume Cadiot, Samira M. Sadowski, Frédéric Triponez, Hélène Du Boullay, Pierre Goudet, and Olivier Chabre
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congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,medicine.medical_specialty ,ddc:617 ,endocrine system diseases ,Long term follow up ,business.industry ,030209 endocrinology & metabolism ,Neuroendocrine tumors ,medicine.disease ,3. Good health ,Surgery ,Conservative treatment ,Natural history ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,MEN1 ,Multiple endocrine neoplasia ,business ,Prospective cohort study ,Cause of death - Abstract
Objective:To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET).Background:Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinic
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- 2018
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4. Subclinical Hypothyroidism: is it Really Subclinical with Aging?
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Pierre-Yves Brard, Anne-Sophie Gauchez, Thomas Gilbert, Anne Charrié, Claire Falandry, Charles Thivolet, A. Mayer, Robin Gourmelon, Catherine Ronin, Karim Chikh, Raphaëlle Andréani, Antoine Vignoles, Sandrine Donadio-Andréi, Marc Bonnefoy, Anne François-Joubert, Domitille Guédel, Christine Waterlot, Jean-Cyril Bourre, Emmanuel Disse, Muriel Rabilloud, Elisabetta Kuczewski, Hélène Du Boullay, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Département de médecine nucléaire, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Départment de Biochimie, Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Michallon, Laboratoire Sols et Environnement (LSE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Hôpital de Chambery, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiopharmaceutiques biocliniques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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0301 basic medicine ,medicine.medical_specialty ,endocrine system diseases ,[SDV]Life Sciences [q-bio] ,Population ,Reference range ,Gastroenterology ,Orginal Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Older patients ,Internal medicine ,medicine ,In patient ,Euthyroid ,education ,Subclinical infection ,education.field_of_study ,business.industry ,Tsh ,aging ,Cell Biology ,thyroid deficiency ,Aged patients ,030104 developmental biology ,Multicenter study ,symptoms ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - Abstract
No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged \textless60 years (\textless60y) and 531 subjects \textgreater/=60 years (\textgreater/=60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH vs euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 vs 1.6, p\textless0.01) than in the SCH population (2.3 vs 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the \textless60y group (p\textless0.01). The percentage of subjects with at least 3 signs increased with SCH in the \textless60y group (42.6% vs 25.0%, p\textless0.01) but not \textgreater/=60y (34.4% vs 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 vs 0.27, p\textless0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients \textless60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction.
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- 2019
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5. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study
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Bruno Vergès, Albert Beckers, Brigitte Delemer, Vincent Rohmer, Arnaud Murat, Jean-Marc Kuhn, Philippe Ruszniewski, Christine Binquet, Julien Thevenon, Philippe Caron, Georges Weryha, Michel Rodier, Sophie Giraud, F. Archambeaud, I. Guilhem, Morgane Le Bras, Philippe Chanson, Béatrice Parfait, Jean-Louis Sadoul, Lionel Groussin, Patricia Niccoli, Catherine Cardot-Bauters, Philippe Bouchard, Eric Baudin, Françoise Duron, Michel Renard, Hélène Bihan, Véronique Kerlan, P. Lecomte, Catherine Lombard-Bohas, Abderrahmane Bourredjem, Anne Barlier, Emilie Castermans, Françoise Borson-Chazot, Bernard Goichot, Olivier Chabre, Antoine Tabarin, Alain Calender, Laurence Faivre, Hélène Du Boullay, Pierre Goudet, Eric Clauser, Alfred Penfornis, Marie-Françoise Odou, Université Joseph Fourier - Grenoble 1 ( UJF ), Immunovirologie et polymorphisme génétique, Université de Nantes ( UN ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Centre de recherche en neurobiologie - neurophysiologie de Marseille ( CRN2M ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Service d'Endocrinologie ( BORDEAUX - Endocrino ), CHU Bordeaux [Bordeaux], Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Biologie du Cancer et de l'Infection ( BCI - UMR S1036 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), Service d'Endocrinologie ( LIEGE - Endocrino ), Université de Liège, Department of Gastroenterology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Pathologie et virologie moléculaire ( PVM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne ( URCA ) -Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire [Rennes], Service d'Endocrinologie ( ANGERS - Endocrino ), CHU Angers, Département de Médecine Interne et Nutrition, CHU Strasbourg, Service d'Endocrinologie ( TOULOUSE - Endocrino ), CHU Toulouse [Toulouse], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Endocrinologie ( TOURS - Endocrino ), CHRU Tours, Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Conservatoire National des Arts et Métiers - Paris ( CNAM Paris ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Médecine interne B, Endocrinologie, Diabète, Maladies métaboliques [CHU Limoges], CHU Limoges, Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Service d'Endocrinologie ( CHRU - Endocrino ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service de Diabétologie, Service des maladies métaboliques et endocriniennes, Hôpital Universitaire Carémeau [Nîmes], Service d'Endocrinologie ( NICE - Endocrino ), CHU Nice, Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) ( PCVP / CARDIO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), Université Joseph Fourier - Grenoble 1 (UJF), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service d'Endocrinologie (BORDEAUX - Endocrino), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie (LIEGE - Endocrino), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologie et virologie moléculaire (PVM (UMR_7151)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Endocrinologie (ANGERS - Endocrino), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Endocrinologie (TOULOUSE - Endocrino), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service d'Endocrinologie (CHRU - Endocrino), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), Université de Nantes (UN), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Brest (UBO), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Fédération d'endocrinologie, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)
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Oncology ,Male ,endocrine system diseases ,Proto-Oncogene Proteins c-jun ,[SDV]Life Sciences [q-bio] ,Disease ,medicine.disease_cause ,MESH: Protein Structure, Tertiary ,0302 clinical medicine ,Risk Factors ,MESH: Risk Factors ,MESH : Female ,Genetics (clinical) ,Mutation ,General Medicine ,MESH: Follow-Up Studies ,MESH : Risk Factors ,3. Good health ,030220 oncology & carcinogenesis ,Cohort ,MESH : Proto-Oncogene Proteins ,Female ,MESH : Mutation ,MESH : Protein Structure, Tertiary ,MESH : Proto-Oncogene Proteins c-jun ,MESH : Multiple Endocrine Neoplasia Type 1 ,Cohort study ,medicine.medical_specialty ,endocrine system ,MESH: Mutation ,Genetic counseling ,MESH : Male ,MESH: Multiple Endocrine Neoplasia Type 1 ,030209 endocrinology & metabolism ,Biology ,03 medical and health sciences ,Internal medicine ,Proto-Oncogene Proteins ,Genetics ,medicine ,Multiple Endocrine Neoplasia Type 1 ,Humans ,MEN1 ,Family ,Molecular Biology ,MESH: Family ,MESH: Humans ,MESH: Proto-Oncogene Proteins c-jun ,[ SDV ] Life Sciences [q-bio] ,Proportional hazards model ,MESH : Humans ,Cancer ,MESH : Follow-Up Studies ,medicine.disease ,MESH: Male ,Protein Structure, Tertiary ,MESH: Proto-Oncogene Proteins ,Cancer research ,MESH : Family ,MESH: Female ,Follow-Up Studies - Abstract
International audience; Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.
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- 2013
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6. Clinical characteristics and outcome of acromegaly induced by ectopic secretion of growth hormone-releasing hormone (GHRH): a French nationwide series of 21 cases
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Françoise Borson-Chazot, Antoine Tabarin, Olivier Chabre, Ihab Nakib, Fabrice Bonnet, Laetitia Garby, Gwenaëlle Arnault, Francine Claustrat, Hélène du-Boullay, Gérald Raverot, Arnaud Murat, Philippe Caron, Bruno Claustrat, Philippe Chanson, Geneviève Sassolas, Sophie Christin-Maitre, Vincent Rohmer, Jean-Louis Sadoul, Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Service d'Endocrinologie (TOULOUSE - Endocrino), CHU Toulouse [Toulouse], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service d'Endocrinologie (BORDEAUX - Endocrino), CHU Bordeaux [Bordeaux], Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des maladies génétiques d'expression pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), registre rhone-alpin du cancer de la thyroide, Eq 4, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est-Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Scanella, Marie-Pierre
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Endoscopic ultrasound ,Male ,MESH: Registries ,MESH: Carcinoid Tumor ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Neuroendocrine tumors ,Growth Hormone-Releasing Hormone ,Biochemistry ,0302 clinical medicine ,Endocrinology ,MESH: Growth Hormone-Releasing Hormone ,Medicine ,Registries ,MESH: Bronchial Neoplasms ,MESH: Treatment Outcome ,MESH: Aged ,Sermorelin ,MESH: Middle Aged ,medicine.diagnostic_test ,Bronchial Neoplasms ,MESH: Follow-Up Studies ,Middle Aged ,Growth hormone–releasing hormone ,Prognosis ,3. Good health ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Somatostatin ,Treatment Outcome ,MESH: Growth Hormone-Secreting Pituitary Adenoma ,030220 oncology & carcinogenesis ,Female ,France ,MESH: Pancreatic Neoplasms ,Pancreas ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Adult ,medicine.medical_specialty ,endocrine system ,Adolescent ,MESH: Neuroendocrine Tumors ,MESH: Multiple Endocrine Neoplasia Type 1 ,030209 endocrinology & metabolism ,Context (language use) ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Carcinoid Tumor ,MESH: Prognosis ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Acromegaly ,Multiple Endocrine Neoplasia Type 1 ,Humans ,Pituitary Neoplasms ,MESH: Pituitary Neoplasms ,Aged ,MESH: Adolescent ,MESH: Humans ,business.industry ,Biochemistry (medical) ,MESH: Adult ,medicine.disease ,MESH: Male ,Pancreatic Neoplasms ,MESH: France ,Growth Hormone-Secreting Pituitary Adenoma ,business ,MESH: Acromegaly ,MESH: Female ,Follow-Up Studies - Abstract
International audience; CONTEXT: Ectopic GHRH secretion is a rare cause of acromegaly, and case reports are mainly isolated. SETTING: From the registry of the sole laboratory performing plasma GHRH assays in France, we identified cases of ectopic GHRH secretion presenting with acromegaly between 1983 and 2008. PATIENTS: Twenty-one patients aged 14-77 yr were identified from 12 French hospitals. Median GHRH was 548 (270-9779) ng/liter. MAIN OUTCOME MEASURES: Outcome measures included description of tumor features and outcome and the relation between plasma GHRH values and tumor site, size, and spread. RESULTS: The primary neuroendocrine tumor was identified for 20 of 21 patients (12 pancreatic, seven bronchial, one appendicular). Tumors were large (10-80 mm), identified on computed tomography scan in 18 cases and by endoscopic ultrasound and somatostatin receptor scintigraphy in two. Somatostatin receptor scintigraphy had a similar sensitivity to computed tomography scan (81 vs. 86%). Tumors were all well differentiated; 47.6% had metastasized at the time of diagnosis of acromegaly. After a median follow-up of 5 yr, 85% of patients were alive. Ninety-one percent of patients whose tumor was completely removed were considered in remission, and most had normalized plasma GHRH. The remaining patients were treated with somatostatin analogs: IGF-I normalized except for one patient who required pegvisomant, but GHRH levels remained elevated. No correlations were found between GHRH levels and tumor site or size or the existence of metastases. Identification of increased plasma GHRH during follow-up was an accurate indicator of recurrence. CONCLUSIONS: The prognosis of endocrine tumors responsible for GHRH secretion appears relatively good. Plasma GHRH assay is an accurate tool for diagnosis and follow-up.
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- 2012
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7. A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes
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Slawomir Wolczynski, Thierry Brue, Claire Bouvattier, Philippe Rondard, Isabelle Arnulf, Anne Guiochon-Mantel, F. Despert, Sylvie Cabrol, Paolo Tonella, Philippe Bouchard, Maria Ramos-Arroyo, Jean-Pierre Hardelin, Sylvie Brailly-Tabard, Michèle Mathieu, Jacques Young, Catherine Dodé, Gérard Reach, Graeme Morgan, Nathalie Chabbert-Buffet, Alfons Garcia-Piñero, James Lespinasse, Nicole De Talence, Arnaud Murat, Sébastien Jacquemont, Julie Sarfati, Bruno Delobel, Catherine Bremont, Anne Lienhardt-Roussie, Zinet Turki, Maud Bidet, Michel Pugeat, Hélène Du Boullay, Bernard Conrad, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Head of the Department of Medical Genetics, Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-GHICL, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie et Maladies de la reproduction, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)
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Male ,Hydrocortisone ,Kallmann syndrome ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,MESH: Receptors, G-Protein-Coupled ,medicine.disease_cause ,MESH: Neuropeptides ,Biochemistry ,Body Mass Index ,Receptors, G-Protein-Coupled ,Basal (phylogenetics) ,0302 clinical medicine ,Endocrinology ,Cryptorchidism ,Testis ,Testosterone ,MESH: Gastrointestinal Hormones ,10. No inequality ,2. Zero hunger ,0303 health sciences ,Mutation ,030219 obstetrics & reproductive medicine ,MESH: Testis ,Phenotype ,MESH: Hydrocortisone ,Circadian Rhythm ,Microphallus ,MESH: Kallmann Syndrome ,Female ,medicine.medical_specialty ,MESH: Mutation ,Receptors, Peptide ,MESH: Testosterone ,Context (language use) ,Biology ,MESH: Phenotype ,MESH: Body Mass Index ,Gastrointestinal Hormones ,03 medical and health sciences ,MESH: Cryptorchidism ,Internal medicine ,medicine ,Humans ,MESH: Circadian Rhythm ,Allele ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Alleles ,030304 developmental biology ,MESH: Receptors, Peptide ,MESH: Humans ,MESH: Alleles ,Biochemistry (medical) ,Neuropeptides ,Prokineticin receptor 2 ,Kallmann Syndrome ,medicine.disease ,biology.organism_classification ,MESH: Male ,MESH: Female - Abstract
International audience; Context: Both biallelic and monoallelic mutations in PROK2 or PROKR2 have been found in Kallmann syndrome (KS). Objective: The objective of the study was to compare the phenotypes of KS patients harboring monoallelic and biallelic mutations in these genes. Design and Patients: We studied clinical and endocrine features that reflect the functioning of the pituitary-gonadal axis, and the nonreproductive phenotype, in 55 adult KS patients (42 men and 13 women), of whom 41 had monoallelic mutations and 14 biallelic mutations in PROK2 or PROKR2. Results: Biallelic mutations were associated with more frequent cryptorchidism (70% vs. 34%, P < 0.05) and microphallus (90% vs. 28%, P < 0.001) and lower mean testicular volume (1.2 +/- 0.4 vs. 4.5 +/- 6.0 ml; P < 0.01) in male patients. Likewise, the testosterone level as well as the basal FSH level and peak LH level under GnRH-stimulation were lower in males with biallelic mutations (0.2 +/- 0.1 vs. 0.7 +/- 0.8 ng/ml; P = 0.05, 0.3 +/- 0.1 vs. 1.8 +/- 3.0 IU/liter; P < 0.05, and 0.8 +/- 0.8 vs. 5.2 +/- 5.5 IU/liter; P < 0.05, respectively). Nonreproductive, nonolfactory anomalies were rare in both sexes and were never found in patients with biallelic mutations. The mean body mass index of the patients (23.9 +/- 4.2 kg/m(2) in males and 26.3 +/- 6.6 kg/m(2) in females) did not differ significantly from that of gender-, age-, and treatment-matched KS individuals who did not carry a mutation in PROK2 or PROKR2. Finally, circadian cortisol levels evaluated in five patients, including one with biallelic PROKR2 mutations, were normal in all cases. Conclusion: Male patients carrying biallelic mutations in PROK2 or PROKR2 have a less variable and on average a more severe reproductive phenotype than patients carrying monoallelic mutations in these genes. Nonreproductive, nonolfactory clinical anomalies associated with KS seem to be restricted to patients with monoallelic mutations.
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- 2009
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8. Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome
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Chrystel Leroy, Jean-Pierre Hardelin, James Lespinasse, Sébastien Jacquemont, Hélène Du Boullay, Catherine Dodé, Marc Delpech, Sandrine Leclercq, Jean-Michel Dupont, and Corinne Fouveaut
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Kallmann syndrome ,DNA Mutational Analysis ,Biology ,medicine.disease_cause ,Compound heterozygosity ,Frameshift mutation ,Gastrointestinal Hormones ,Mice ,Gene interaction ,Hypogonadotropic hypogonadism ,Internal medicine ,Genetics ,medicine ,Missense mutation ,Animals ,Humans ,Genetics (clinical) ,Alleles ,Mutation ,Fibroblast growth factor receptor 1 ,Neuropeptides ,Kallmann Syndrome ,medicine.disease ,Pedigree ,Endocrinology ,Female - Abstract
Kallmann syndrome is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Putative loss-of-function mutations in PROKR2 or PROK2, encoding prokineticin receptor-2 (a G protein-coupled receptor), and one of its ligands, prokineticin-2, respectively, have recently been reported in approximately 10% of Kallmann syndrome affected individuals. Notably, given PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state in patients, thus raising the question of a possible digenic inheritance of the disease in heterozygous patients. Indeed, one of these patients was also carrying a missense mutation in KAL1, the gene responsible for the X chromosome-linked form of Kallmann syndrome. Mutations in PROK2, however, have so far been found only in the heterozygous state. Here, we report on the identification of PROK2 biallelic mutations, that is, a missense mutation, p.R73C, and a frameshift mutation, c.163delA, in two out of 273 patients presenting as sporadic cases. We conclude that PROK2 mutations in the homozygous state account for a few cases of Kallmann syndrome. Moreover, since the same R73C mutation was previously reported in the heterozygous state, and because Prok2 knockout mice exhibit an abnormal phenotype only in the homozygous condition, we predict that patients carrying monoallelic mutations in PROK2 have another disease-causing mutation, presumably in still undiscovered Kallmann syndrome genes.
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- 2008
9. Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1
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Arnaud Murat, Eric Baudin, Catherine Cardot-Bauters, Olivier Chabre, Laurence Thomas-Marques, Brigitte Delemer, Groupe français des tumeurs endocrines, Patricia Niccoli-Sire, Nicolas Jovenin, Damien Levoir, Hélène du Boullay Choplin, Alfred Penfornis, and Guillaume Cadiot
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Pancreatic Polypeptide ,Severity of Illness Index ,Endosonography ,Diagnosis, Differential ,Duodenal Neoplasms ,Gastrins ,medicine ,Biomarkers, Tumor ,Multiple Endocrine Neoplasia Type 1 ,Endocrine system ,Humans ,In patient ,Prospective Studies ,Multiple endocrine neoplasia ,Prospective cohort study ,Aged ,Hepatology ,medicine.diagnostic_test ,business.industry ,Incidence ,Disease progression ,Gastroenterology ,Follow up studies ,Middle Aged ,medicine.disease ,Glucagon ,Surgery ,Endoscopy ,Pancreatic Neoplasms ,Multicenter study ,Disease Progression ,Female ,Radiology ,business ,Peptides ,Follow-Up Studies ,Vasoactive Intestinal Peptide - Abstract
The frequency of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1 (MEN1) remains unknown.To evaluate prospectively with endoscopic ultrasonography (EUS) the frequency of nonfunctioning (asymptomatic) pancreaticoduodenal tumors.MEN1 patients without functioning pancreatic involvement underwent systematic pancreaticoduodenal EUS in nine GTE (Groupe des Tumeurs Endocrines) centers. Demographic and clinical factors predictive of pancreatic involvement were sought, and standardized biochemical measurements obtained.Between November 1997 and July 2004, 51 patients (median age: 39 [range: 16-71] yr) were studied. MEN1 had been diagnosed 3 [0-20] yr earlier, notably by genetic screening for 26 (51%) with asymptomatic disease. Twenty-five patients had minor biochemical anomalies (2 x normal (N)) and serum somatostatin was 10.8 N in 1; EUS detected pancreatic lesions in 28 patients (54.9%; 95% CI: 41.3-68.7%). A median of three [1-9] tumors with a median diameter of 6 [2-60] mm was found per patient; for 19 (37.3%) patients a tumor measuredor =10 mm andor = 20 mm in 7 (13.7%) patients. Only one duodenal lesion was found and three patients had peripancreatic adenopathies. Pancreatic tumors were not associated with any of the studied parameters, notably age, family history, biochemical anomalies. Sixteen of twenty-six patients underwent EUS monitoring over 50 [12-70] months; six (37.5%) had more and/or larger pancreatic lesions.The frequency of nonfunctioning pancreatic endocrine tumors is higher (54.9%) than previously thought. The size and number of these tumors can increase over time. Pancreatic EUS should be performed once MEN1 is diagnosed to monitor disease progression.
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- 2006
10. Prospective Endoscopic Ultrasonographic Evaluation of the Frequency of Nonfunctioning Pancreaticoduodenal Endocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1.
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Thomas-Marques, Laurence, Murat, Arnaud, Delemer, Brigitte, Penfornis, Alfred, Cardot-Bauters, Catherine, Baudin, Eric, Niccoli-Sire, Patricia, Levoir, Damien, Choplin, Hélène du Boullay, Chabre, Olivier, Jovenin, Nicolas, and Cadiot, Guillaume
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PANCREATIC tumors ,PANCREAS ,ENDOSCOPIC ultrasonography ,DIAGNOSTIC ultrasonic imaging ,SOMATOSTATIN ,PEPTIDE hormones - Abstract
BACKGROUND: The frequency of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1 (MEN1) remains unknown. AIM: To evaluate prospectively with endoscopic ultrasonography (EUS) the frequency of nonfunctioning (asymptomatic) pancreaticoduodenal tumors. PATIENTS AND METHODS: MEN1 patients without functioning pancreatic involvement underwent systematic pancreaticoduodenal EUS in nine GTE (Groupe des Tumeurs Endocrines) centers. Demographic and clinical factors predictive of pancreatic involvement were sought, and standardized biochemical measurements obtained. RESULTS: Between November 1997 and July 2004, 51 patients (median age: 39 [range: 16–71] yr) were studied. MEN1 had been diagnosed 3 [0–20] yr earlier, notably by genetic screening for 26 (51%) with asymptomatic disease. Twenty-five patients had minor biochemical anomalies (<2 × normal (N)) and serum somatostatin was 10.8 N in 1; EUS detected pancreatic lesions in 28 patients (54.9%; 95% CI: 41.3–68.7%). A median of three [1–9] tumors with a median diameter of 6 [2–60] mm was found per patient; for 19 (37.3%) patients a tumor measured ≥10 mm and ≥ 20 mm in 7 (13.7%) patients. Only one duodenal lesion was found and three patients had peripancreatic adenopathies. Pancreatic tumors were not associated with any of the studied parameters, notably age, family history, biochemical anomalies. Sixteen of twenty-six patients underwent EUS monitoring over 50 [12–70] months; six (37.5%) had more and/or larger pancreatic lesions. CONCLUSION: The frequency of nonfunctioning pancreatic endocrine tumors is higher (54.9%) than previously thought. The size and number of these tumors can increase over time. Pancreatic EUS should be performed once MEN1 is diagnosed to monitor disease progression. [ABSTRACT FROM AUTHOR]
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- 2006
- Full Text
- View/download PDF
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