Different Somatic Mutations in Multinodular Adrenals With Aldosterone-Producing Adenoma

作者：Fernandes Rosa Fabio Luiz; Giscos Douriez Isabelle; Amar Laurence; Gomez Sanchez Celso E; Meatchi Tchao; Boulkroun Sheerazed; Zennaro Maria Christina^*

来源：Hypertension, 2015, 66(5): 1014-1022.

DOI：10.1161/HYPERTENSIONAHA.115.05993

• adrenal cortex
• aldosterone
• hyperaldosteronism
• mineralocorticoids
• mutation
• potassium channels

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.

• 出版日期2015-11