Abstract：
:Hereditary adrenal pheochromocytoma is caused by germline mutations in RET, VHL, SDHB, SDHD, and NF1. As these genes differ in function, so may their pheochromocytoma phenotypes, suggesting gene-specific patterns of age-related progression to pheochromocytoma. This possibility was explored for gene carriers with a lifetime risk of pheochromocytoma in excess of 50%. Published age-standardized penetrance rates of VHL-, SDHB-, and SDHD-associated pheochromocytoma were gauged against age-standardized penetrance rates of MEN2-associated pheochromocytoma in 219 institutional carriers of RET mutations conferring highest (codon 918), high (codons 609, 611, 618, 620, 630, and 634) and least high risk (codons 768, 790, 791, 804, and 891). The highest-risk category included SDHB, SDHD, and the highest-risk RET genotype; the high-risk category VHL missense mutations and the high-risk RET genotypes; and the least-high risk category VHL truncating mutations and least-high risk RET genotypes. Detailed information on recurrence rates and intervals was available only for the RET carriers (19-31% and means of 4.3-5.5 years; all RET risk categories combined). Ipsilateral recurrences in adrenal remnants, and contralateral recurrences in virgin adrenals were comparable in incidence (27% and 39%, P=0.69; high-risk RET category) and time to recurrence (means of 4.3 vs. 5.4 year; P>0.99; high-risk RET category), discounting a major effect of tumor spillage at primary subtotal adrenalectomy on pheochromocytoma recurrence. The risk of malignancy usually is low, except for SDHB (38%). For most hereditary pheochromocytomas, endoscopic subtotal adrenalectomy is the procedure of choice. Grouping hereditary pheochromocytoma into preliminary risk categories may improve the management of gene carriers at risk of developing pheochromocytomas.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Machens A,Brauckhoff M,Gimm O,Dralle Hdoi
10.1196/annals.1353.045subject
Has Abstractpub_date
2006-08-01 00:00:00pages
417-28eissn
0077-8923issn
1749-6632pii
1073/1/417journal_volume
1073pub_type
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