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Laura Fugazzola Department of Clinical Sciences and Community Health, University of Milan and Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy

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Calcitonin, the Marker of Medullary Thyroid Cancer Medullary thyroid cancer (MTC) can be a very aggressive tumor. Significant differences in survival have been reported according to the stage of the tumor at the time of diagnosis, the survival

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Fabio Maino Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Cristina Dalmiglio Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Nicoletta Benenati Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Michele Campanile Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Tania Pilli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Raffaella Forleo Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Lucia Brilli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Cristina Ciuoli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Silvia Cantara Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Marco Capezzone Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Alessandra Cartocci Department of Medical Biotechnologies, University of Siena, Siena, Italy

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Furio Pacini Humanitas Clinical Institute, Humanitas University, Rozzano, Italy

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Maria Grazia Castagna Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Introduction Calcitonin (CT), a 32-amino acid calcium-lowering peptide secreted by the C-cells (parafollicular cells) of the thyroid, is used as a marker for the diagnosis and the follow-up of medullary thyroid cancer (MTC) [ 1 ]. In patients

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Else Marie Opsahl Section of Breast- and Endocrine Surgery, Department of Oncology, Oslo University Hospital, Oslo, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway

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Lars Andreas Akslen Section for Pathology, Department of Clinical Medicine, Centre for Cancer Biomarkers CCBIO, University of Bergen, Bergen, Norway
Department of Pathology, Haukeland University Hospital Bergen, Bergen, Norway

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Ellen Schlichting Section of Breast- and Endocrine Surgery, Department of Oncology, Oslo University Hospital, Oslo, Norway

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Turid Aas Department of Breast- and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway

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Katrin Brauckhoff Department of Breast- and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway

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Anne Irene Hagen Department of Breast- and Endocrine Surgery, St. Olavs University Hospital, Trondheim, Norway

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Alf Frimann Rosenlund Section of Breast- and Endocrine Surgery, Department of Surgery, University Hospital of North Norway, Tromsø, Norway

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Eva Sigstad Department of Pathology, Oslo University Hospital, Oslo, Norway

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Krystyna K. Grøholt Department of Pathology, Oslo University Hospital, Oslo, Norway

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Lars H. Jørgensen Department of Thoracic Surgery, Oslo University Hospital, Oslo, Norway

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Trine Bjøro Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

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disease in the lateral neck [ 3 , 14 ]. High-resolution ultrasound is important in disease staging, enabling the detection of even very small metastatic lymph nodes but not micrometastases. Calcitonin is a good tumor marker in MTC. As a rule, it is

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Cléber P. Camacho Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo

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Susan C. Lindsey Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo

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Teresa S. Kasamatsu Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo

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Alberto L. Machado Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo
Fleury Medicine and Health, São Paulo, Brazil

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João Roberto M. Martins Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo

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Rosa Paula M. Biscolla Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo
Fleury Medicine and Health, São Paulo, Brazil

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Magnus R. Dias da Silva Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo

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José Gilberto H. Vieira Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo
Fleury Medicine and Health, São Paulo, Brazil

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Rui M.B. Maciel Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo
Fleury Medicine and Health, São Paulo, Brazil

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Introduction Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC) and is employed for its diagnosis and follow-up monitoring [ 1 ]. In addition, some guidelines advocate sCT measurements for the differential

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Renata Alencar Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil
Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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Daniel Barretto Kendler Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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Fernanda Andrade Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Carla Nava Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Daniel Bulzico Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Cencita Cordeiro de Noronha Pessoa Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Rossana Corbo Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil
Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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Fernanda Vaisman Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil
Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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monitored after for serum levels of calcitonin and carcinoembryonic antigen (CEA) usually twice or three times a year. After 2015, CA19-9 serum levels were also routinely measured in these patients and were collected usually at each semester. Imaging tests

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Isabelle Clinckspoor Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Anne-Catherine Gérard Pôle de Morphologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain

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Jacqueline Van Sande IRIBHM, Université Libre de Bruxelles, Brussels

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Marie-Christine Many Pôle de Morphologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain

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Lieve Verlinden Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Roger Bouillon Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Geert Carmeliet Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Chantal Mathieu Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

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Annemieke Verstuyf Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven

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Brigitte Decallonne Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven
Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

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antithyroid antibodies and abnormal thyroid function in humans [ 19 , 20 ], and to modulate autoimmune hyperthyroidism in mice [ 21 ]. Apart from inhibiting osteoclast-mediated bone resorption and increasing renal calcium and phosphate excretion, calcitonin

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Simona Censi Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Elisabetta Cavedon Familial Tumor Unit, Veneto Institute of Oncology, (IOV)-IRCCS, Padua, Italy

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Sara Watutantrige-Fernando Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Susi Barollo Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Loris Bertazza Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Jacopo Manso Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Maurizio Iacobone Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy

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Davide Nacamulli Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Francesca Galuppini Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Gianmaria Pennelli Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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Caterina Mian Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

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What Is Known about This Topic? The most important clinical prognostic factors for medullary thyroid carcinoma are basal serum calcitonin (Ctn) at diagnosis and pathological stage. When the diameter of the primary cancer exceeds 2

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R. Elisei Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

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M. Alevizaki Endocrine Unit, Department of Medical Therapeutics, Athens University School of Medicine, Athens, Greece

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B. Conte-Devolx Department of Endocrinology, La Timone Hospital, Aix Marseille University, Marseille, France

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K. Frank-Raue Endocrine Practice, Molecular Laboratory, Heidelberg, Germany

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V. Leite Department of Endocrinology, Portuguese Institute of Oncology and CEDOC, Faculty of Medical Sciences, Lisbon, Portugal

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G.R. Williams Molecular Endocrinology Group, Department of Medicine, Hammersmith Hospital, Imperial College London, London, UK

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were identified by searching PubMed MEDLINE at PubMed (NLM) using the following search terms: medullary thyroid cancer, RET oncogene, calcitonin, calcium, RET gene carriers, MEN 2, pheochromocytoma, hyperparathyroidism, RET genetic counseling, and

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Catarina Silvestre Department of Endocrinology, Diabetes and Metabolism, Santa Maria Hospital, Lisbon, Portugal

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Joaquim Sampaio Matias Department of Laboratorial Medicine, Santa Maria Hospital, Lisbon, Portugal

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Helena Proença Department of Laboratorial Medicine, Santa Maria Hospital, Lisbon, Portugal

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Maria João Bugalho Department of Endocrinology, Diabetes and Metabolism, Santa Maria Hospital, Lisbon, Portugal

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Introduction Calcitonin (Ctn) is a 32-amino acid polypeptide secreted by the parafollicular cells of the thyroid, called “C” cells. With a known important role in regulating blood calcium in fish and rodents, the role of Ctn in human calcium

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Abbas Al-Kurd Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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David J. Gross Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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David Zangen Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Karine Atlan Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Haggi Mazeh Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Simona Grozinsky-Glasberg Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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should be revised to recommend calcitonin screening and prophylactic thyroidectomy at an earlier age in such patients. Due to the rarity of these patients, cumulative literature on the topic is essential, and, therefore, reports such as the present one

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