Endocrine Connections (Jun 2020)
Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study
- 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
Affiliations
- Louise Vølund Larsen
- Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark
- Delphine Mirebeau-Prunier
- Laboratoire de Biochimie et Biologie Moléculaire, CHU Angers, Université d’Angers, UMR CNRS 6015, INSERM U1083, MITOVASC, Angers, France
- Tsuneo Imai
- Department of Breast & Endocrine Surgery, National Hospital Organization, Higashinagoya National Hospital, Nagoya, Japan
- Cristina Alvarez-Escola
- Endocrinology and Nutrition Department, University Hospital ‘La Paz’, Madrid, Spain
- Kornelia Hasse-Lazar
- Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
- Simona Censi
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Luciana A Castroneves
- Department of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Akihiro Sakurai
- Department of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, Sapporo, Japan
- Minoru Kihara
- Department of Surgery, Kuma Hospital, Kobe, Hyogo, Japan
- Kiyomi Horiuchi
- Department of Breast and Endocrine Surgery, Tokyo Women’s Medical University, Tokyo, Japan
- Véronique Dorine Barbu
- AP-HP, Sorbonne Université, Laboratoire Commun de Biologie et Génétique Moléculaires, Hôpital St Antoine & INSERM CRSA, Paris, France; Réseau TenGen, Marseille, France
- Francoise Borson-Chazot
- Réseau TenGen, Marseille, France; Fédération d’Endocrinologie, Hospices Civils de Lyon, Université Lyon 1, France
- Anne-Paule Gimenez-Roqueplo
- Réseau TenGen, Marseille, France; Service de Génétique, AP-HP, Hôpital européen Georges Pompidou, Paris, France; Université de Paris, PARCC, INSERM, Paris, France
- Pascal Pigny
- Réseau TenGen, Marseille, France; Laboratoire de Biochimie et Oncologie Moléculaire, CHU Lille, Lille, France
- Stephane Pinson
- Réseau TenGen, Marseille, France; Laboratoire de Génétique Moléculaire, CHU Lyon, Lyon, France
- Nelson Wohllk
- Endocrine Section, Hospital del Salvador, Santiago de Chile, Department of Medicine, University of Chile, Santiago, Chile
- Charis Eng
- Genomic Medicine Institute, Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
- Berna Imge Aydogan
- Department of Endocrinology And Metabolic Diseases, Ankara University School of Medicine, Ankara, Turkey
- Dhananjaya Saranath
- Department of Research Studies & Additional Projects, Cancer Patients Aid Association, Dr. Vithaldas Parmar Research & Medical Centre, Worli, Mumbai, India
- Sarka Dvorakova
- Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic
- Frederic Castinetti
- Aix-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, France
- Attila Patocs
- HAS-SE Momentum Hereditary Endocrine Tumors Research Group, Semmelweis University, Budapest, Hungary
- Damijan Bergant
- Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia
- Thera P Links
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Mariola Peczkowska
- Department of Hypertension, Institute of Cardiology, Warsaw, Poland
- Ana O Hoff
- Department of Endocrinology, Endocrine Oncology Unit, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Caterina Mian
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
- Trisha Dwight
- Cancer Genetics, Kolling Institute, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia
- Barbara Jarzab
- Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
- Hartmut P H Neumann
- Section for Preventive Medicine, Medical Center-University of Freiburg, Faculty of Medicine, Albert Ludwigs-University of Freiburg, Freiburg, Germany
- Mercedes Robledo
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
- Shinya Uchino
- Department of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita, Japan
- Anne Barlier
- Réseau TenGen, Marseille, France; Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology, Hospital La Conception, Marseille, France
- Christian Godballe
- Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark
- Jes Sloth Mathiesen
- Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- DOI
- https://doi.org/10.1530/EC-20-0163
- Journal volume & issue
-
Vol. 9,
no. 6
pp. 489 – 497
Abstract
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.
Keywords
- primary hyperparathyroidism
- multiple endocrine neoplasia type 2a
- ret
- medullary thyroid carcinoma
- pheochromocytoma
