Emerging methods for subtype differentiation in primary aldosteronism

Primary aldosteronism (PA) is a common cause of hypertension. Compared to patients with essential hypertension, untreated PA is associated with a two- to fourfold greater risk of cardiovascular disease, renal failure, and death. PA is caused by increased secretion of aldosterone from one adrenal gland in 30% of the patients and both adrenal glands in 70%. Patients with unilateral PA can be cured by adrenalectomy, whereas patients with bilateral PA should be treated with mineralocorticoid receptor antagonists. With these disease-specific treatments, the long-term prognosis is generally favorable. A major challenge in the management of patients with PA is, however, subtype differentiation, that is, to determine whether the disease is unilateral or bilateral. Adrenal imaging using CT or MRI misclassifies more than one third of patients, and clinical variables-including blood pressure, aldosterone, and renin concentrations-provide limited guidance, underscoring the need for more accurate diagnostic approaches. Adrenal vein sampling is currently considered the gold standard for this purpose, but it is a technically challenging procedure performed only in specialized centers. After adrenalectomy for unilateral PA, histopathological assessment and subtyping are crucial for determining postoperative prognosis. This process is complex and relies on detailed functional analyses that are not always straightforward to interpret. Therefore, new approaches for subtyping PA are required. In this review, we summarize recent advances in the management of patients with PA, with particular focus on the limitations of current approaches to subtype differentiation and the emerging roles of novel techniques, including positron emission tomography, steroidomics, proteomics, and transcriptomics.