Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study
Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to esti...
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Bioscientifica
2020-06-01
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Series: | Endocrine Connections |
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Online Access: | https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0163.xml |
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doaj-fce9b24b992c46119c9143129797252c |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Louise Vølund Larsen Delphine Mirebeau-Prunier Tsuneo Imai Cristina Alvarez-Escola Kornelia Hasse-Lazar Simona Censi Luciana A Castroneves Akihiro Sakurai Minoru Kihara Kiyomi Horiuchi Véronique Dorine Barbu Francoise Borson-Chazot Anne-Paule Gimenez-Roqueplo Pascal Pigny Stephane Pinson Nelson Wohllk Charis Eng Berna Imge Aydogan Dhananjaya Saranath Sarka Dvorakova Frederic Castinetti Attila Patocs Damijan Bergant Thera P Links Mariola Peczkowska Ana O Hoff Caterina Mian Trisha Dwight Barbara Jarzab Hartmut P H Neumann Mercedes Robledo Shinya Uchino Anne Barlier Christian Godballe Jes Sloth Mathiesen |
spellingShingle |
Louise Vølund Larsen Delphine Mirebeau-Prunier Tsuneo Imai Cristina Alvarez-Escola Kornelia Hasse-Lazar Simona Censi Luciana A Castroneves Akihiro Sakurai Minoru Kihara Kiyomi Horiuchi Véronique Dorine Barbu Francoise Borson-Chazot Anne-Paule Gimenez-Roqueplo Pascal Pigny Stephane Pinson Nelson Wohllk Charis Eng Berna Imge Aydogan Dhananjaya Saranath Sarka Dvorakova Frederic Castinetti Attila Patocs Damijan Bergant Thera P Links Mariola Peczkowska Ana O Hoff Caterina Mian Trisha Dwight Barbara Jarzab Hartmut P H Neumann Mercedes Robledo Shinya Uchino Anne Barlier Christian Godballe Jes Sloth Mathiesen Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study Endocrine Connections primary hyperparathyroidism multiple endocrine neoplasia type 2a ret medullary thyroid carcinoma pheochromocytoma |
author_facet |
Louise Vølund Larsen Delphine Mirebeau-Prunier Tsuneo Imai Cristina Alvarez-Escola Kornelia Hasse-Lazar Simona Censi Luciana A Castroneves Akihiro Sakurai Minoru Kihara Kiyomi Horiuchi Véronique Dorine Barbu Francoise Borson-Chazot Anne-Paule Gimenez-Roqueplo Pascal Pigny Stephane Pinson Nelson Wohllk Charis Eng Berna Imge Aydogan Dhananjaya Saranath Sarka Dvorakova Frederic Castinetti Attila Patocs Damijan Bergant Thera P Links Mariola Peczkowska Ana O Hoff Caterina Mian Trisha Dwight Barbara Jarzab Hartmut P H Neumann Mercedes Robledo Shinya Uchino Anne Barlier Christian Godballe Jes Sloth Mathiesen |
author_sort |
Louise Vølund Larsen |
title |
Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study |
title_short |
Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study |
title_full |
Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study |
title_fullStr |
Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study |
title_full_unstemmed |
Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study |
title_sort |
primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2a: an international multicenter study |
publisher |
Bioscientifica |
series |
Endocrine Connections |
issn |
2049-3614 2049-3614 |
publishDate |
2020-06-01 |
description |
Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A i ndex cases and to characterize the former cases.
Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registr y data of index cases followed from 1974 to 2017.
Results: Ten cases presented with PHPT as their first manifestation of M EN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.
Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of i ndex cases presenting with PHPT as first manifestation have synchronous MTC and are often n ode-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resecti on of PHPT.
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topic |
primary hyperparathyroidism multiple endocrine neoplasia type 2a ret medullary thyroid carcinoma pheochromocytoma |
url |
https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0163.xml |
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doaj-fce9b24b992c46119c9143129797252c2020-11-25T03:25:33ZengBioscientificaEndocrine Connections2049-36142049-36142020-06-0196489497https://doi.org/10.1530/EC-20-0163Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter studyLouise Vølund Larsen0Delphine Mirebeau-Prunier1Tsuneo Imai2Cristina Alvarez-Escola3Kornelia Hasse-Lazar4Simona Censi5Luciana A Castroneves6Akihiro Sakurai7Minoru Kihara8Kiyomi Horiuchi9Véronique Dorine Barbu10Francoise Borson-Chazot11Anne-Paule Gimenez-Roqueplo12Pascal Pigny13Stephane Pinson14Nelson Wohllk15Charis Eng16Berna Imge Aydogan17Dhananjaya Saranath18Sarka Dvorakova19Frederic Castinetti20Attila Patocs21Damijan Bergant22Thera P Links23Mariola Peczkowska24Ana O Hoff25Caterina Mian26Trisha Dwight27Barbara Jarzab28Hartmut P H Neumann29Mercedes Robledo30Shinya Uchino31Anne Barlier32Christian Godballe33Jes Sloth Mathiesen34Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, DenmarkLaboratoire de Biochimie et Biologie Moléculaire, CHU Angers, Université d’Angers, UMR CNRS 6015, INSERM U1083, MITOVASC, Angers, FranceDepartment of Breast & Endocrine Surgery, National Hospital Organization, Higashinagoya National Hospital, Nagoya, JapanEndocrinology and Nutrition Department, University Hospital ‘La Paz’, Madrid, SpainDepartment of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, PolandEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyDepartment of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilDepartment of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, Sapporo, JapanDepartment of Surgery, Kuma Hospital, Kobe, Hyogo, JapanDepartment of Breast and Endocrine Surgery, Tokyo Women’s Medical University, Tokyo, JapanAP-HP, Sorbonne Université, Laboratoire Commun de Biologie et Génétique Moléculaires, Hôpital St Antoine & INSERM CRSA, Paris, France; Réseau TenGen, Marseille, France Réseau TenGen, Marseille, France; Fédération d’Endocrinologie, Hospices Civils de Lyon, Université Lyon 1, FranceRéseau TenGen, Marseille, France; Service de Génétique, AP-HP, Hôpital européen Georges Pompidou, Paris, France; Université de Paris, PARCC, INSERM, Paris, FranceRéseau TenGen, Marseille, France; Laboratoire de Biochimie et Oncologie Moléculaire, CHU Lille, Lille, FranceRéseau TenGen, Marseille, France; Laboratoire de Génétique Moléculaire, CHU Lyon, Lyon, FranceEndocrine Section, Hospital del Salvador, Santiago de Chile, Department of Medicine, University of Chile, Santiago, ChileGenomic Medicine Institute, Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USADepartment of Endocrinology And Metabolic Diseases, Ankara University School of Medicine, Ankara, TurkeyDepartment of Research Studies & Additional Projects, Cancer Patients Aid Association, Dr. Vithaldas Parmar Research & Medical Centre, Worli, Mumbai, IndiaDepartment of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech RepublicAix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France; Department of Endocrinology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, FranceHAS-SE Momentum Hereditary Endocrine Tumors Research Group, Semmelweis University, Budapest, HungaryDepartment of Surgical Oncology, Institute of Oncology, Ljubljana, SloveniaDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Hypertension, Institute of Cardiology, Warsaw, PolandDepartment of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilEndocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, ItalyCancer Genetics, Kolling Institute, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, AustraliaDepartment of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, PolandSection for Preventive Medicine, Medical Center-University of Freiburg, Faculty of Medicine, Albert Ludwigs-University of Freiburg, Freiburg, GermanyHereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, SpainDepartment of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita, JapanRéseau TenGen, Marseille, France; Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology, Hospital La Conception, Marseille, FranceDepartment of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, DenmarkDepartment of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, DenmarkObjective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A i ndex cases and to characterize the former cases. Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registr y data of index cases followed from 1974 to 2017. Results: Ten cases presented with PHPT as their first manifestation of M EN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of i ndex cases presenting with PHPT as first manifestation have synchronous MTC and are often n ode-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resecti on of PHPT. https://ec.bioscientifica.com/view/journals/ec/9/6/EC-20-0163.xmlprimary hyperparathyroidismmultiple endocrine neoplasia type 2aretmedullary thyroid carcinomapheochromocytoma |