title: When is prophylactic thyroidectomy indicated for patients with the RET codon 609 mutation?
abstract: BACKGROUND
  Mutations in the RET proto-oncogene cause multiple endocrine neoplasia type 2A (MEN2A), and prophylactic thyroidectomy has generally been recommended before the age of 5 years. Patients with codon 609 mutations develop MTC at a later age and therefore the timing of prophylactic thyroidectomy is less clear. We report a three-generation family with C609Y RET mutation where members having prophylactic or therapeutic thyroidectomy call the current recommendations for age at thyroidectomy into question.
  
  
  METHODS
  Sixteen family members underwent thyroidectomy, for which clinical, laboratory, and pathological data were analyzed. A literature review of RET codon 609 mutations was carried out.
  
  
  RESULTS
  Data were collected from 16 patients from this 38-member kindred. None of these affected members had pheochromocytoma, and one had a parathyroid adenoma. Nine of 16 patients had MTC (mean age 44.7 years, range 29-59 years) and elevated basal calcitonin levels; 6 of these 9 had lymph node metastases. Two patients had C-cell hyperplasia (CCH) at ages 18 and 37 years, and five patients had normal thyroid pathology (mean age 16 years, range 5-37 years). In the literature, a family with C609Y mutation was reported, with 15 members having MTC (mean age 42 years, range 21-59 years), and 6 with CCH (mean age 24 years, range 15-37 years).
  
  
  CONCLUSIONS
  The youngest patient with C609Y RET mutation and MTC was 21 years old, and the youngest patient with CCH was 15 years old at diagnosis. These data suggest that patients with RET C609Y mutations can delay thyroidectomy until 10-15 years of age, with annual calcitonin screening prior to thyroidectomy.
authors.affiliation: Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa College of Medicine, Iowa City, IA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Calva
authors.forename: Thomas M
authors.initials: TM
authors.lastname: O'Dorisio
authors.forename: M
authors.initials: M
authors.lastname: Sue O'Dorisio
authors.forename: Geeta
authors.initials: G
authors.lastname: Lal
authors.forename: Sonia
authors.initials: S
authors.lastname: Sugg
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Weigel
authors.forename: James R
authors.initials: JR
authors.lastname: Howe
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000601:surgery; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000235:genetics / Q000601:surgery; D002291:Carcinoma, Papillary / Q000235:genetics / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000601:surgery; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics / Q000601:surgery; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D015415:Biomarkers; D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human