Subtypes of Histopathologically Classical Aldosterone-Producing Adenomas Yield Various Transcriptomic Signaling and Outcomes

There have been no reports of outcome differences between distinctive subgroups in patients with unilateral primary aldosteronism with histopathologically classical adenomas. The characteristics and incidence of complete clinical success in the patients with unilateral primary aldosteronism could be associated with the concomitant existence of multiple aldosterone-producing micronodules/nodules. Altogether, 74 classical adenomas (mean, 52.9 years and 40 men [54.1%]) were identified among 98 operated patients with unilateral primary aldosteronism. Among them accompanying multiple aldosterone-producing micronodules/nodules (group A) were identified in 38 (51.3%) of the adrenal glands; these patients showed lower likelihood (42.1%) to achieve complete clinical success than that (80.6%) of those with aldosterone-producing adenoma/nodules alone (group B, P =0.001). Additionally, group A adenomas were associated with less complete clinical success (odds ratio, 5.53, P =0.005) in the multivariable regression analysis. Group A patients also had higher baseline aldosterone production (absolute aldosterone ratio) from the contralateral adrenal gland ( P =0.039). Based on the patterns of genes with highly differential expressions as uncovered by RNA-seq analysis, Group A adenomas showed distinct transcriptomic profiles in comparison to the gene expressions from Group B adenomas. Pathway enrichment analysis revealed that HTR2B-mediated calcium pathway, in terms of HTR2B , and PLCE1 was prominently downregulated in Group A adenomas. There was 51.3% of the patients with unilateral primary aldosteronism with classical group A adenomas. These patients were more likely to have hypertension-persistence after adrenalectomy. The functional signatures of Group A adenomas showed attenuated HTR2B-mediated PLC/IP3/Ca2 + pathway; this may provide some mechanistic explanation to various clinical outcomes.