When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations?
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.
Niccoli-Sire
Patricia
P
Department of Endocrinology and Endocrine Surgery, CHU Timone, 254 rue St Pierre, F 13385 Marseille cedex 05, France.
Murat
Arnaud
A
Rohmer
Vincent
V
Gibelin
Hélène
H
Chabrier
Gerard
G
Conte-Devolx
Bernard
B
Visset
Jacques
J
Ronceray
Jean
J
Jaeck
Daniel
D
Henry
Jean François
JF
Proye
Charles
C
Carnaille
Bruno
B
Kraimps
Jean Louis
JL
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
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