Codon-specific development of pheochromocytoma in multiple endocrine neoplasia type 2.
BACKGROUND
Recent data suggest a codon-specific, age-related development of multiple endocrine neoplasia type 2.


OBJECTIVE
The objective of this study was to delineate the codon-specific, age-related development of multiple endocrine neoplasia type 2-associated pheochromocytoma.


METHODS
We describe a cohort study with a mean observation period of 26.9 yr.


METHODS
The study took place in a tertiary referral center at a university hospital.


METHODS
Included in this study were 206 consecutive carriers (74 index, 132 nonindex) operated on at this institution who harbored point mutations in the RET (rearranged during transfection) protooncogene.


METHODS
The intervention was adrenalectomy for clinically confirmed pheochromocytoma.


METHODS
The main outcome measure was time to histopathological diagnosis of pheochromocytoma.


RESULTS
Pheochromocytomas developed in 28% (five of 18) of carriers with mutations in codon 918, 29% (20 of 68) of carriers with mutations in codon 634, 14% (three of 21) of carriers with mutations in codon 618, 13% (two of 16) of carriers with mutations in codon 620, and 13% (two of 16) of carriers with mutations in codon 791. Earliest age of manifestation for each genotype was 22, 18, 29, 22, and 39 yr. Contralateral pheochromocytomas developed after 4 yr (one carrier each had a mutation in codon 618 or 620) and 5.2 yr (six carriers had mutations in codon 634). No pheochromocytomas were identified in carriers of mutations in codons 609 (n = 2), 611 (n = 8), 630 (n = 2), 768 (n = 8), 790 (n = 22), 804 (n = 18), and 891 (n = 7).


CONCLUSIONS
Based on these and published preliminary data, annual screening for pheochromocytoma may be warranted from age 10 yr in carriers of RET mutations in codons 918, 634, and 630, and from age 20 yr in the remainder.
Machens
Andreas
A
Department of General, Visceral, and Vascular Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06097 Halle (Saale), Germany. gensurg@medizin.uni-halle.de
Brauckhoff
Michael
M
Holzhausen
Hans-Jürgen
HJ
Thanh
Phuong Nguyen
PN
Lehnert
Hendrik
H
Dralle
Henning
H
D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000315:Adrenalectomy; D000328:Adult; D003062:Codon; D015331:Cohort Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012306:Risk
D003062:Codon; D015513:Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases