Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D are found in aldosterone producing adenoma. Additionally, 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, four showed the same mutation in a secondary nodule, while ten had no mutation in any of the known genes. In one adrenal harboring the KCNJ5 p.Gly151Arg mutation in the principal nodule, the same mutation was present in two secondary nodules, but no mutation was found in a third nodule. Finally, in two adrenals with a CACNA1D mutation in the principal nodule, a KCNJ5 mutation was identified in the secondary nodule. Among ten adrenals without mutations in the principal nodule, one carried a KCNJ5 mutation in the secondary nodule. No mutations were detected in seven aldosterone producing cell clusters from six 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.