Targeting cholesterol-dependent adrenal steroidogenesis for management of primary aldosteronism

Primary aldosteronism (PA) is a common, salt-sensitive form of endocrine hypertension. Compared with essential hypertension (EH), PA is more susceptible to cardiorenal complications and metabolic risks. However, PA has a low screening rate and a poor response to mineralocorticoid receptor antagonists (MRAs). In addition to somatic ion channel mutations and epigenetic alterations, which contribute to excessive production of aldosterone, cholesterol, as a crucial precursor for aldosterone biosynthesis, may be involved in PA pathogenesis. Abnormal adrenal cholesterol uptake and steroidogenesis have been found in patients with PA. Therefore, we propose that a statin-based therapeutic strategy may be pivotal for antagonizing PA-related comorbidities by targeting cholesterol-dependent adrenal steroidogenesis.