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Article Dans Une Revue The Lancet. Diabetes & Endocrinology Année : 2019

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study

Steven Waguespack
  • Fonction : Auteur
Andreas Machens
  • Fonction : Auteur
Shinya Uchino
  • Fonction : Auteur
Kornelia Lazaar
  • Fonction : Auteur
Gabriella Sanso
  • Fonction : Auteur
Tobias Else
  • Fonction : Auteur
Sarka Dvorakova
Xiao Qi
  • Fonction : Auteur
Rossella Elisei
John Glod
  • Fonction : Auteur
Delmar Muniz Lourenço
  • Fonction : Auteur
Nuria Valdes
  • Fonction : Auteur
Jes Mathiesen
  • Fonction : Auteur
Tushar Bandgar
  • Fonction : Auteur
Maralyn Druce
  • Fonction : Auteur
Caroline Brain
  • Fonction : Auteur
Tom Kurzawinski
  • Fonction : Auteur
Atila Patocs
  • Fonction : Auteur
Maria Bugalho
  • Fonction : Auteur
André Lacroix
  • Fonction : Auteur
Philippe Caron
Patricia Fainstein-Day
  • Fonction : Auteur
Marc Klein
  • Fonction : Auteur
Thera Links
  • Fonction : Auteur
Laura Fugazzola
  • Fonction : Auteur
Antoine Tabarin
  • Fonction : Auteur
Anita Spehar Uroic
  • Fonction : Auteur
Dominique Maiter
  • Fonction : Auteur
Sandrine Laboureau
  • Fonction : Auteur
  • PersonId : 1070111
Laurence Leclerc
  • Fonction : Auteur
Birke Bausch
  • Fonction : Auteur
Akihiro Sukurai
  • Fonction : Auteur
Petr Vlcek
  • Fonction : Auteur
Jolanta Krajewska
  • Fonction : Auteur
Carla Vaz Ferreira Vargas
  • Fonction : Auteur
Laura Valerio
  • Fonction : Auteur
Lucieli Ceolin
  • Fonction : Auteur
Srivandana Akshintala
  • Fonction : Auteur
Ana Hoff
  • Fonction : Auteur
Christian Godballe
  • Fonction : Auteur
Barbara Jarzab
  • Fonction : Auteur
Camilo Jimenez
  • Fonction : Auteur
Tsuneo Imai
  • Fonction : Auteur
Elizabeth Grubbs
  • Fonction : Auteur
Henning Dralle
  • Fonction : Auteur
Hartmut Neumann
  • Fonction : Auteur
Eric Baudin

Résumé

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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hal-02616929 , version 1 (20-12-2021)

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Frederic Castinetti, Steven Waguespack, Andreas Machens, Shinya Uchino, Kornelia Lazaar, et al.. Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study. The Lancet. Diabetes & Endocrinology , 2019, 7 (3), pp.213-220. ⟨10.1016/S2213-8587(18)30336-X⟩. ⟨hal-02616929⟩
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