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Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study
F. Castinetti, SG. Waguespack, A. Machens, S. Uchino, K. Hasse-Lazar, G. Sanso, T. Else, S. Dvorakova, XP. Qi, R. Elisei, AL. Maia, J. Glod, DM. Lourenço, N. Valdes, J. Mathiesen, N. Wohllk, TR. Bandgar, D. Drui, M. Korbonits, MR. Druce, C....
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, multicentrická studie, práce podpořená grantem
Grantová podpora
NV16-32665A
MZ0
CEP - Centrální evidence projektů
- MeSH
- dítě MeSH
- dospělí MeSH
- feochromocytom mortalita patologie chirurgie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezinárodní agentury MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mnohočetná endokrinní neoplazie typ 2B mortalita patologie chirurgie MeSH
- nádory nadledvin mortalita patologie chirurgie MeSH
- nádory štítné žlázy mortalita patologie chirurgie MeSH
- následné studie MeSH
- neuroendokrinní karcinom mortalita patologie chirurgie MeSH
- předškolní dítě MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- tyreoidektomie mortalita MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.
Centro Académico de Medicina de Lisboa Universidade Lisboa Lisboa Portugal
Département de Biochimie et Génétique Centre Hospitalier Universitaire d'Angers Angers France
Department of Clinical Research University of Southern Denmark Odense Denmark
Department of Endocrine Surgery La Conception Hospital Marseille France
Department of Endocrinology and Nutrition Hospital Universitario Central de Asturias Oviedo Spain
Department of Endocrinology St Bartholomew's Hospital London UK
Department of Endocrinology University Hospital Nancy France
Department of Endocrinology University Hospital Pisa Italy
Department of Hypertension Institute of Cardiology Warsaw Poland
Department of Internal Medicine and Medical Specialties Sapienza University of Rome Rome Italy
Department of Molecular Endocrinology Institute of Endocrinology Prague Czech Republic
Department of Pathophysiology and Transplantation University of Milan Milan Italy
Department of Pediatrics New York University Langone Medical Center New York NY USA
Department of Pediatrics University Hospital Centre Zagreb Zagreb Croatia
Department of Surgical Oncology University of Texas MD Anderson Cancer Center Houston TX USA
Endocrine and Nuclear Medicine Unit Hospital Italiano de Buenos Aires Buenos Aires Argentina
Endocrine Oncology Institut Gustave Roussy Ecole Doctorale de Cancerologie Villejuif France
Endocrine Section Universidad de Chile Hospital del Salvador Santiago de Chile Santiago Chile
Endocrinologie et Métabolismes Centre Hospitalier de Saint Denis Saint Denis France
Hospices Civils de Lyon Fédération d'Endocrinologie Université Claude Bernard Lyon 1 Lyon France
London School of Medicine and Dentistry Queen Mary University of London London UK
Motol University Hospital Prague Czech Republic
Noguchi Thyroid Clinic and Hospital Foundation Beppu Japan
Operative Unit of the Endocrinology Department of Medicine University of Padua Padua Italy
Pediatric Oncology Branch National Cancer Institute National Institutes of Health Bethesda MD USA
Section for Preventive Medicine Department of Nephrology and General Medicine Freiburg Germany
Citace poskytuje Crossref.org
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- $a Castinetti, Frederic $u Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Marseille Medical Genetics, Marseille, France; Assistance Publique-Hôpitaux de Marseille, Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l'hypophyse, Marseille, France. Electronic address: frederic.castinetti@ap-hm.fr.
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- $a Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study / $c F. Castinetti, SG. Waguespack, A. Machens, S. Uchino, K. Hasse-Lazar, G. Sanso, T. Else, S. Dvorakova, XP. Qi, R. Elisei, AL. Maia, J. Glod, DM. Lourenço, N. Valdes, J. Mathiesen, N. Wohllk, TR. Bandgar, D. Drui, M. Korbonits, MR. Druce, C. Brain, T. Kurzawinski, A. Patocs, MJ. Bugalho, A. Lacroix, P. Caron, P. Fainstein-Day, F. Borson Chazot, M. Klein, TP. Links, C. Letizia, L. Fugazzola, O. Chabre, L. Canu, R. Cohen, A. Tabarin, A. Spehar Uroic, D. Maiter, S. Laboureau, C. Mian, M. Peczkowska, F. Sebag, T. Brue, D. Mirebeau-Prunier, L. Leclerc, B. Bausch, A. Berdelou, A. Sukurai, P. Vlcek, J. Krajewska, M. Barontini, C. Vaz Ferreira Vargas, L. Valerio, L. Ceolin, S. Akshintala, A. Hoff, C. Godballe, B. Jarzab, C. Jimenez, C. Eng, T. Imai, M. Schlumberger, E. Grubbs, H. Dralle, HP. Neumann, E. Baudin,
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- $a BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.
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- 700 1_
- $a Waguespack, Steven G $u Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 700 1_
- $a Machens, Andreas $u Department of General, Visceral and Vascular Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
- 700 1_
- $a Uchino, Shinya $u Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Japan.
- 700 1_
- $a Hasse-Lazar, Kornelia $u Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Gliwice, Poland.
- 700 1_
- $a Sanso, Gabriella $u Centro de Investigaciones Endocrinológicas, "Dr César Bergadá", Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
- 700 1_
- $a Else, Tobias $u Division of Metabolism, Endocrinology, & Diabetes, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
- 700 1_
- $a Dvorakova, Sarka $u Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
- 700 1_
- $a Qi, Xiao Ping $u Departments of Oncologic and Urologic Surgery, The 117th People's Liberation Army Hospital, People's Liberation Army Hangzhou Clinical College, Anhui Medical University, Hangzhou, China.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Valdes, Nuria $u Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias, Oviedo, Spain; Unit of Endocrinology, Nutrition, Diabetes and Obesity, Institute of Sanitary Research of Asturias, Oviedo, Spain.
- 700 1_
- $a Mathiesen, Jes $u Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
- 700 1_
- $a Wohllk, Nelson $u Endocrine Section, Universidad de Chile, Hospital del Salvador, Santiago de Chile, Santiago, Chile.
- 700 1_
- $a Bandgar, Tushar R $u Department of Endocrinology, Seth G S Medical College, King Edward Memorial Hospital, Parel, Mumbai, India.
- 700 1_
- $a Drui, Delphine $u L'Institut du thorax, Department of Endocrinology, Centre Hospitalier Universitaire Nantes, Nantes, France.
- 700 1_
- $a Korbonits, Marta $u Department of Endocrinology, St Bartholomew's Hospital, London, UK; London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- 700 1_
- $a Druce, Maralyn R $u Department of Endocrinology, St Bartholomew's Hospital, London, UK; London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- 700 1_
- $a Brain, Caroline $u Division of Endocrine Surgery, University College Hospital and Great Ormond Street Hospital, London, United Kingdom.
- 700 1_
- $a Kurzawinski, Tom $u Division of Endocrine Surgery, University College Hospital and Great Ormond Street Hospital, London, United Kingdom.
- 700 1_
- $a Patocs, Atila $u Hungarian Academy of Sciences and Semmelweis University, HSA-SE "Lendület" Hereditary Endocrine Tumour Research Group, Budapest, Hungary.
- 700 1_
- $a Bugalho, Maria Joao $u Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar Universitário Lisboa Norte-Hospital Santa Maria, Lisboa, Portugal; Centro Académico de Medicina de Lisboa, Universidade Lisboa, Lisboa, Portugal.
- 700 1_
- $a Lacroix, Andre $u Endocrine Division, Department of Medicine, Centre Hospitalier de l'Universite í de Montréal, Montreal, QC, Canada.
- 700 1_
- $a Caron, Philippe $u Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey, Service d'Endocrinologie, Maladies métaboliques, Nutrition, Toulouse, France.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Letizia, Claudio $u Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
- 700 1_
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- 700 1_
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- 700 1_
- $a Canu, Letizia $u Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Bausch, Birke $u Section for Preventive Medicine, Department of Nephrology and General Medicine, Freiburg, Germany.
- 700 1_
- $a Berdelou, Amandine $u Endocrine Oncology, Institut Gustave Roussy Ecole Doctorale de Cancerologie, Villejuif, France.
- 700 1_
- $a Sukurai, Akihiro $u Department of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Hokkaido, Japan.
- 700 1_
- $a Vlcek, Petr $u Department of Nuclear Medicine and Endocrinology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Motol University Hospital, Prague, Czech Republic.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Grubbs, Elizabeth $u Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 700 1_
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- 700 1_
- $a Neumann, Hartmut P $u Section for Preventive Medicine, Department of Nephrology and General Medicine, Freiburg, Germany.
- 700 1_
- $a Baudin, Eric $u Endocrine Oncology, Institut Gustave Roussy Ecole Doctorale de Cancerologie, Villejuif, France.
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