title: Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update.
abstract: BACKGROUND
  Over the last decade, our knowledge of the multiple endocrine neoplasia (MEN) type 2 syndromes MEN2A and MEN2B and familial medullary thyroid carcinoma (FMTC) has expanded greatly. In this manuscript, we summarize how recent discoveries have enhanced our understanding of the molecular basis of these diseases and led to improvements in the diagnosis and management of affected patients.
  
  
  METHODS
  We reviewed the English literature through PubMed from 2000 to the present, using the search terms medullary thyroid carcinoma, multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma, RET proto-oncogene, and calcitonin.
  
  
  RESULTS
  Over 70 RET mutations are known to cause MEN2A, MEN2B, or FMTC, and recent findings from studies of large kindreds with these syndromes have clouded the relationship between genotype and phenotype, primarily because of the varied clinical presentation of different families with the same RET mutation. This clinical variability has also confounded decisions about the timing of prophylactic thyroidectomy for MTC, the dominant endocrinopathy associated with these syndromes. A distinct advance has been the demonstration through phase II and phase III clinical trials that molecular targeted therapeutics are effective in the treatment of patients with locally advanced or metastatic MTC.
  
  
  CONCLUSIONS
  The effective management of patients with MEN2A, MEN2A, and FMTC depends on an understanding of the variable behavior of disease expression in patients with a specific RET mutation. Information gained from molecular testing, biochemical analysis, and clinical evaluation is important in providing effective management of patients with either early or advanced-stage MTC.
authors.affiliation: Cancer Genetics Branch, National Cancer Institute, National Institutes of Health, Building 37, Room 10106A, 37 Convent Drive, Bethesda, Maryland 20814, USA. wellss@mail.nih.gov
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wells
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
mesh_terms: D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000150:complications / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D005838:Genotype; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D013965:Thyroidectomy
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human