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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.

The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring KCNJ5 mutations with or without subclinical hypercortisolism remain unclear. This prospective study is aimed at determining factors associated with subclinical hypercortisolism in patients with clinical aldosterone-producing adenomas. Totally, 82 patients were recruited from November 2016 to March 2018 and underwent unilateral laparoscopic adrenalectomy with at least a 12-month follow-up postoperatively. Standard subclinical hypercortisolism (defined as cortisol >1.8 μg/dL after 1 mg dexamethasone suppression test [DST]) was detected in 22 (26.8%) of the 82 patients. Intriguingly, a generalized additive model identified the clinical aldosterone-producing adenoma patients with 1 mg DST>1.5 μg/dL had significantly larger tumors ( P =0.02) than those with 1 mg DSTKCNJ5 mutations (odds ratio, 0.22, P =0.010) and body mass index (odds ratio, 0.87, P =0.046) were negatively associated with 1 mg DST>1.5 μg/dL, whereas tumor size was positively associated with it (odds ratio, 2.85, P =0.014). Immunohistochemistry revealed a higher degree of immunoreactivity for CYP11B1 in adenomas with wild-type KCNJ5 ( P =0.018), whereas CYP11B2 was more commonly detected in adenomas with KCNJ5 mutation ( P =0.007). Patients with wild-type KCNJ5 and 1 mg DST>1.5 μg/dL exhibited the lowest complete clinical success rate (36.8%) after adrenalectomy. In conclusion, subclinical hypercortisolism is common in clinical aldosterone-producing adenoma patients without KCNJ5 mutation or with a relatively larger adrenal tumor. The presence of serum cortisol levels >1.5 μg/dL after 1 mg DST may be linked to a lower clinical complete success rate.