Multiple Endocrine Neoplasia Type 2

Mark J.C. van Treijen; Lisa H. de Vries; Doenja Hertog; Menno R. Vriens; Annemarie A. Verrijn Stuart; Bernadette P.M. van Nesselrooij; Gerlof D. Valk

Multiple Endocrine Neoplasia Type 2

Review

In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

2022 Jan 2.

Authors

Mark J.C. van Treijen¹, Lisa H. de Vries², Doenja Hertog³, Menno R. Vriens⁴, Annemarie A. Verrijn Stuart⁵, Bernadette P.M. van Nesselrooij⁶, Gerlof D. Valk⁷

Book Editors

Kenneth R Feingold¹, Bradley Anawalt², Marc R Blackman³, Alison Boyce⁴, George Chrousos⁵, Emiliano Corpas⁶, Wouter W de Herder⁷, Ketan Dhatariya⁸, Kathleen Dungan⁹, Johannes Hofland¹⁰, Sanjay Kalra¹¹, Gregory Kaltsas¹², Nitin Kapoor¹³, Christian Koch¹⁴, Peter Kopp¹⁵, Márta Korbonits¹⁶, Christopher S Kovacs¹⁷, Wendy Kuohung¹⁸, Blandine Laferrère¹⁹, Miles Levy²⁰, Elizabeth A McGee²¹, Robert McLachlan²², Maria New²³, Jonathan Purnell²⁴, Rakesh Sahay²⁵, Amy S Shah²⁶, Frederick Singer²⁷, Mark A Sperling²⁸, Constantine A Stratakis²⁹, Dace L Trence³⁰, Don P Wilson³¹

Affiliations

¹ Endocrinologist, Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
² Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
³ Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁴ Professor of Endocrine Surgical oncology, Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁵ Pediatric endocrinologist, Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
⁶ Clinical geneticist, Department of Medical Genetics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
⁷ Professor in Endocrine Oncology, Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, the Netherlands

Book Affiliations

¹ Professor of Medicine Emeritus, University of California, San Francisco, CA
² Chief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
³ Sr. Physician Scientist, Washington DC VA Medical Center; Professor of Medicine & Rehabilitation Medicine, Georgetown University; Clinical Professor of Medicine, Biochemistry and Molecular Medicine, George Washington University; and Professor of Medicine (Part-time), Johns Hopkins University
⁴ Pediatric Endocrinologist and Associate Research Physician in the Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health
⁵ Professor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece
⁶ M.D. Ph.D in Gerontology. Honorary Professor of Medicine, Universidad de Alcalá, Madrid. Consultant in Endocrinology, Hospital HLA Guadalajara (Spain).
⁷ Professor of Endocrine Oncology, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
⁸ Consultant in Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK.
⁹ Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
¹⁰ Consultant Endocrinologist, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
¹¹ Consultant Endocrinologist, Department of Endocrinology, Bharti Hospital, Karnal, India
¹² Professor of General Medicine-Endocrinology, 1st Department of Propaedeutic Medicine, National and Kapodistrian University of Athens, Athens, Greece
¹³ Professor of Endocrinology, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
¹⁴ Professor, The University of Tennessee Health Science Center, Memphis, Tennessee
¹⁵ Professor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
¹⁶ Professor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, England
¹⁷ University Research Professor and Professor of Medicine (Endocrinology and Metabolism), Obstetrics & Gynecology, and BioMedical Sciences, at Memorial University of Newfoundland in St. John’s, Newfoundland, Canada.
¹⁸ Director of the Division of Reproductive Endocrinology at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at the Boston University School of Medicine
¹⁹ Professor of Medicine, New York Nutrition Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
²⁰ Consultant endocrinologist at University Hospitals of Leicester and Honorary Associate Professor at Leicester University
²¹ Professor of Obstetrics and Gynecology at the University of Vermont and Director of the Division of Reproductive Endocrinology and Infertility. Burlington, Vermont
²² Director of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
²³ Professor of Pediatrics, Professor of Genetics and Genomic Sciences, and Chief of the Adrenal Steroid Disorders Program, Icahn School of Medicine, Mount Sinai School of Medicine, New York, NY
²⁴ Professor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, OR
²⁵ Professor and Head of Department of Endocrinology, Osmania Medical College and Osmania General Hospital, Hyderabad, India.
²⁶ Professor of Pediatrics, The University of Cincinnati, Department of Pediatrics and Cincinnati Children’s Hospital Medical Center, Division of Endocrinology, Cincinnati, OH, USA
²⁷ Director of the Endocrine/Bone Disease Program, Saint Johns Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, CA
²⁸ Professorial Lecturer, Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY. Emeritus Professor and Chair, Department of Pediatrics, University of Pittsburgh.
²⁹ CSO, ELPEN, Inc. & Director, Research Institute, Athens, Greece & Senior Investigator, Human Genetics & Precision Medicine, FORTH (ITE), Heraklion, Greece. Emeritus Scientific Director & Senior Investigator, NICHD, NIH, Bethesda, MD, USA
³⁰ Professor of Medicine, Emeritus, University of Washington, Seattle, WA
³¹ Endowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

PMID: 29465928
Bookshelf ID: NBK481898

Excerpt

Multiple Endocrine Neoplasia (MEN) type 2 A and B are rare autosomal dominant inherited cancer syndromes characterized by tumors of the C cells of the thyroid, of the adrenal medulla, and parathyroid glands. MEN2 is caused by a genetic defect in the REarranged during Transfection (RET) proto-oncogene on chromosome 10 (10q11-2), leading to a ligand-independent activation of the transmembrane RET receptor tyrosine kinase and consequently its intra-cellular pathways. Different mutations lead to different levels of activation and MEN2 is therefore characterized by a strong genotype-phenotype correlation. Nearly all patients with MEN2A have either C-cell hyperplasia (CCH) or medullary thyroid cancer (MTC), 50% have pheochromocytoma (PHEO), and 20-30% hyperparathyroidism (pHPT) but incidence of these manifestations is depending on the underlying RET mutation. Patients with MEN2B have a 100% incidence of CCH or MTC, PHEO in 30-50%, mucosal neuromas, and rarely pHPT. Endocrine tumors in MEN2 are often multifocal and bilateral. Nowadays, the diagnosis of MEN2 is made by genetic testing. After diagnosis, annual screening for associated manifestations and prophylactic thyroidectomy for preventing metastasized MTC are advised. Optimal age for preventive surgery or when to start screening for each manifestation is based upon the underlying RET mutation. In patients with MTC present at diagnosis, adequate staging is needed before surgical resection, since surgery is the only curative treatment. The most important biomarker for MTC is calcitonin. Fractionated metanephrines are used for early diagnosing PHEO and calcium and PTH for hyperparathyroidism. For PHEO, a minimal invasive surgical resection is recommended. In pHPT the surgical approach should be tailored to the amount and location of the enlarged glands visualized with imaging. Recurrent MTC requires physical examination, neck ultrasound, and measurement of serum calcitonin and carcinoembryonic antigen (CEA) levels every 6 months. For metastasized MTC, treatment can be successful with multikinase inhibitors (vandetanib, cabozantinib) and selective RET inhibitors (pralsetinib, selpercatinib). For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

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