In:
European Journal of Endocrinology, Oxford University Press (OUP), Vol. 172, No. 6 ( 2015-06), p. 677-685
Abstract:
Cortisol excess due to adrenal adenomas or hyperplasia causes Cushing's syndrome. Recent genetic studies have identified a somatic PRKACA L206R mutation as a cause of cortisol-producing adenomas. We aimed to compare the clinical features of PRKACA -mutant lesions with those of CTNNB1 mutations, and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone. Design, patients, and methods In this study, 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. A total of 36 patients had overt Cushing's syndrome, the remainder were subclinical: 59 cases were adenomas (three bilateral) and one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone. Results Among cortisol-secreting unilateral lesions without evidence of co-secretion ( n =52), we identified somatic mutations in PRKACA (L206R) in 23.1%, CTNNB1 (S45P, S45F) in 23.1%, GNAS (R201C) in 5.8%, and CTNNB1 + GNAS (S45P, R201H) in 1.9%. PRKACA and GNAS mutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations in KCNJ5 (G151R and L168R). The hyperplastic gland showed a PRKACA L206R mutation, while patients with bilateral adenomas did not have known somatic mutations. PRKACA -mutant lesions were associated with younger age, overt Cushing's syndrome, and higher cortisol levels vs non- PRKACA -mutant or CTNNB1 -mutant lesions. CTNNB1 mutations were more significantly associated with right than left lesions. Conclusions PRKACA L206R is present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.
Type of Medium:
Online Resource
ISSN:
0804-4643
,
1479-683X
Language:
Unknown
Publisher:
Oxford University Press (OUP)
Publication Date:
2015
detail.hit.zdb_id:
1485160-X
