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

Published on Mar 1, 2019in The Lancet Diabetes & Endocrinology 19.31
· DOI :10.1016/S2213-8587(18)30336-X
Frederic Castinetti1
Estimated H-index: 1
(French Institute of Health and Medical Research),
Steven G Waguespack37
Estimated H-index: 37
(University of Texas MD Anderson Cancer Center)
+ 63 AuthorsEric Baudin68
Estimated H-index: 68
(Institut Gustave Roussy)
Abstract
Summary 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 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.
  • References (20)
  • Citations (0)
Cite
References20
Published on Mar 26, 2015in Thyroid 7.56
Samuel A. Wells15
Estimated H-index: 15
(National Institutes of Health),
Sylvia L. Asa74
Estimated H-index: 74
(University of Toronto)
+ 15 AuthorsFurio Pacini74
Estimated H-index: 74
(University of Siena)
Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healt...
454 Citations Source Cite
Sonali Thosani5
Estimated H-index: 5
(University of Texas MD Anderson Cancer Center),
Montserrat Ayala-Ramirez11
Estimated H-index: 11
(University of Texas MD Anderson Cancer Center)
+ 7 AuthorsCamilo Jimenez31
Estimated H-index: 31
Context: Pheochromocytoma (PHEO) occurs in 50% of patients with multiple endocrine neoplasia type 2 (MEN2). It is unknown if the presence of PHEO is associated with more aggressive medullary thyroid cancer (MTC). Objective: To present our experience with MEN2 PHEO and evaluate whether PHEO impacts MTC overall survival in patients with RET codon 634 mutations. Design: We performed a retrospective chart review of MEN2 patients at MD Anderson Cancer Center from 1960 through 2012. Patients: The stud...
37 Citations Source Cite
Published on Oct 1, 2011in Nature Reviews Endocrinology 20.27
Steven G Waguespack37
Estimated H-index: 37
,
Thereasa A. Rich19
Estimated H-index: 19
(University of Texas MD Anderson Cancer Center)
+ 2 AuthorsGilbert J. Cote38
Estimated H-index: 38
Medullary thyroid carcinoma is a rare endocrine malignancy that, when diagnosed during childhood, is almost always associated with multiple endocrine neoplasia type 2 and a germline mutation in the RET proto-oncogene. This Review discusses a contemporary approach to the diagnosis and treatment of medullary thyroid carcinoma and multiple endocrine neoplasia type 2 syndromes in the pediatric population.
50 Citations Source Cite
Katrin M. Carlson12
Estimated H-index: 12
(University of Washington),
Shenshen Dou4
Estimated H-index: 4
(University of Washington)
+ 6 AuthorsHelen Donis-Keller32
Estimated H-index: 32
(University of Washington)
Abstract Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals. This sequence differ...
480 Citations Source Cite
Published on Jan 1, 1994in Human Molecular Genetics 4.90
Charis Eng115
Estimated H-index: 115
(Harvard University),
Darrin P. Smith24
Estimated H-index: 24
+ 8 AuthorsAlan Tunnacllffe1
Estimated H-index: 1
The susceptibility loci for the three multiple endocrine neoplasia (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosine kinase. The majority of MEN 2A and familial medullary thyroid carcinoma results from missense mutations within one of five cysteine codons in the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonine for a methio...
416 Citations Source Cite
Published on Dec 1, 2008in Surgery 3.57
Michael Brauckhoff30
Estimated H-index: 30
(University of Bergen),
Andreas Machens36
Estimated H-index: 36
(Martin Luther University of Halle-Wittenberg)
+ 5 AuthorsHenning Dralle68
Estimated H-index: 68
(Martin Luther University of Halle-Wittenberg)
Background. More than 90% of M918T carriers with multiple endocrine neoplasia type 2B (MEN 2B) harbor de novo mutations in the REarranged during Transfection (RET) protooncogene. DNA-based screening for RET germline mutations is rarely useful for early diagnosis, which thus is contingent on the clinical ascertainment of MEN 2B-specifitc symptoms as soon as they emerge. Little information exists about the presence of these symptoms in infancy.Methods. Detailed information was gathered regarding t...
60 Citations Source Cite
Published on Dec 1, 1995in Surgery 3.57
Diarmuid S. O'Riordain5
Estimated H-index: 5
(Mayo Clinic),
O'BrienTimothy61
Estimated H-index: 61
(Mayo Clinic)
+ 3 AuthorsJon A. van Heerden73
Estimated H-index: 73
(Mayo Clinic)
Background. Multiple endocrine neoplasia type 2B (MEN 2B) is a rare disorder differentiated from MEN 2A primarily by its extraendocrine features. This report describes the clinical spectrum and outcome of MEN 2B. Methods. Twenty-one patients underwent operation for manifestations of MEN 2B between 1970 and 1993. Median follow-up was 16.9 years. Diagnosis was made through family screening in nine, the development of medullary thyroid carcinoma (MTC) in seven, phenotypic features in four, and cons...
84 Citations Source Cite
Published on Jan 1, 2002in Cancer 6.54
Sophie Leboulleux50
Estimated H-index: 50
(Institut Gustave Roussy),
Jean-Paul Travagli33
Estimated H-index: 33
(Institut Gustave Roussy)
+ 4 AuthorsEric Baudin68
Estimated H-index: 68
(Institut Gustave Roussy)
BACKGROUND Multiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill-defined. PATIENTS All the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single-center retrospective study. RESULTS There were 9 men and 9 women with a mean age of 13 years (range, 2–27 years) at diagnosis. The diagnosis of MTC was based on the...
79 Citations Source Cite
Published on Nov 20, 1996in JAMA 47.66
Charis Eng115
Estimated H-index: 115
(University of Cambridge),
David F. Clayton58
Estimated H-index: 58
(University of Cambridge)
+ 27 AuthorsShin Ichiro Takai2
Estimated H-index: 2
(Osaka University)
Objective. —Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could h...
904 Citations Source Cite
Published on May 1, 2014in Lancet Oncology 36.42
Frederic Castinetti24
Estimated H-index: 24
(Aix-Marseille University),
Xiao Ping Qi1
Estimated H-index: 1
(Anhui Medical University)
+ 56 AuthorsRodrigo A. Toledo21
Estimated H-index: 21
(University of São Paulo)
Summary Background The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of ph...
46 Citations Source Cite
Cited By0