In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 66, No. 5 ( 2015-11), p. 1014-1022
Abstract:
Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5 , ATP1A1 , ATP2B3 , and CACNA1D are found in aldosterone-producing adenoma. In addition, adrenals with aldosterone-producing adenomas show cortical remodeling and frequently multiple secondary nodules. Our aim was to investigate whether different aldosterone-producing nodules from the same adrenal share the same mutational status. Aldosterone synthase expression was assessed in multinodular adrenals from 27 patients. DNA of 37 aldosterone-producing secondary nodules was extracted from formalin-fixed paraffin-embedded tissues and genotyped for KCNJ5 , ATP1A1 , ATP2B3 , and CACNA1D mutations. Among 17 adrenals with a somatic mutation in the principal nodule, 4 showed the same mutation in a secondary nodule, whereas 10 had no mutation in any of the known genes. In 1 adrenal harboring the KCNJ5 p.Gly151Arg mutation in the principal nodule, the same mutation was present in 2 secondary nodules, but no mutation was found in a third nodule. Finally, in 2 adrenals with a CACNA1D mutation in the principal nodule, a KCNJ5 mutation was identified in the secondary nodule. Among 10 adrenals without mutations in the principal nodule, 1 carried a KCNJ5 mutation in the secondary nodule. No mutations were detected in 7 aldosterone-producing cell clusters from 6 adrenals. No association was observed between the presence of mutations in secondary nodules and clinical parameters. In conclusion, different mutations are found in different aldosterone-producing nodules from the same adrenal, suggesting that somatic mutations are independent events triggered by mechanisms that remain to be identified.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/HYPERTENSIONAHA.115.05993
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
2094210-2
