title: When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations?
abstract: BACKGROUND
  Once familial medullary thyroid carcinoma gene carrier status is established, thyroidectomy must be performed in infancy for mutations in exon 10, but in familial medullary thyroid carcinoma with non-cysteine RET mutations, which is characterized by a late onset of C-cell disease, the appropriate timing of thyroidectomy is unclear.
  
  
  METHODS
  We analyzed the cases of 76 patients who underwent thyroidectomy (mean age, 35.2 years); 66 patients underwent concomitant lymphadenectomy.
  
  
  RESULTS
  Before the operation, 35 patients had abnormal basal calcitonin levels. Nine and 30 patients had negative or positive pentagastrin test results, respectively. We found normal thyroid in 4% of the patients, C-cell hyperplasia in 29% of the patients, medullary thyroid carcinoma in 67% of the patients (microscopic in 82.4%), and nodal metastases in 19.6% of the patients. The aggressiveness of the disease varied significantly between those patients with preoperative positive pentagastrin test results and those patients with high basal calcitonin levels, with a surgical cure rate of 60% and 34.3%, respectively. All patient who did not achieve cure had high basal preoperative calcitonin levels, which were related to macroscopic medullary thyroid carcinoma and nodal metastases in 5 of 9 patients.
  
  
  CONCLUSIONS
  Thyroidectomy should not be delayed until basal calcitonin level becomes abnormal, at which time advanced disease may be present. As soon as the pentagastrin stimulation test becomes abnormal, operation should be undertaken on early staged disease to achieve cure for the patient. When performed while pentagastrin stimulation test is still negative, thyroidectomy may be truly prophylactic and should be recommended at 5 to 6 years.
authors.affiliation: Department of Endocrinology and Endocrine Surgery, CHU Timone, 254 rue St Pierre, F 13385 Marseille cedex 05, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Niccoli-Sire
authors.forename: Arnaud
authors.initials: A
authors.lastname: Murat
authors.forename: Vincent
authors.initials: V
authors.lastname: Rohmer
authors.forename: Hélène
authors.initials: H
authors.lastname: Gibelin
authors.forename: Gerard
authors.initials: G
authors.lastname: Chabrier
authors.forename: Bernard
authors.initials: B
authors.lastname: Conte-Devolx
authors.forename: Jacques
authors.initials: J
authors.lastname: Visset
authors.forename: Jean
authors.initials: J
authors.lastname: Ronceray
authors.forename: Daniel
authors.initials: D
authors.lastname: Jaeck
authors.forename: Jean François
authors.initials: JF
authors.lastname: Henry
authors.forename: Charles
authors.initials: C
authors.lastname: Proye
authors.forename: Bruno
authors.initials: B
authors.lastname: Carnaille
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Kraimps
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000601:surgery*; D002648:Child; D003545:Cysteine / Q000235:genetics; D005768:Gastrointestinal Hormones; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D010418:Pentagastrin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery*; D013965:Thyroidectomy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D005768:Gastrointestinal Hormones; D015513:Oncogene Proteins; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; D010418:Pentagastrin; D003545:Cysteine