New era: prophylactic surgery for patients with multiple endocrine neoplasia-2a.
BACKGROUND
The surgical management of patients with multiple endocrine neoplasia-2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations allowing for a more tailored approach. In this study, we report the surgical management of one of the largest MEN-2A families with a rearranged during transfection (RET) codon 804 mutation.


METHODS
This is a cohort study comprising all at-risk kindred within a single known MEN-2A family. Prophylactic total thyroidectomy with lymph node dissection was recommended to all mutation carriers aged 5 years and older.


RESULTS
There were a total of 48 at-risk individuals in the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate preoperative evaluation. A total of 9 patients had medullary thyroid cancer including 5 with a normal preoperative calcitonin level. A total of 11 patients had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease. Only the index case had a phaeochromocytoma.


CONCLUSIONS
Genetic testing for germline mutations in the RET proto-oncogene has allowed precise identification of affected RET carriers and provided the opportunity for prophylactic or 'preclinical' surgery to treat and in fact to prevent medullary thyroid cancer. This concept of prophylactic surgery based on a genetic test is likely to be applied more widely as the tools of molecular biology advance.
Gosnell
Jessica E
JE
University of Sydney Endocrine Surgery Unit, Sydney, New South Wales, Australia.
Sywak
Mark S
MS
Sidhu
Stan B
SB
Gough
Ian R
IR
Learoyd
Diana L
DL
Robinson
Bruce G
BG
Delbridge
Leigh W
LW
D000293:Adolescent; D000328:Adult; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D011446:Prospective Studies; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D013965:Thyroidectomy / Q000379:methods*; D016896:Treatment Outcome
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human