Over the past 6 years, somatic and germline mutations that cause inappropriate aldosterone production have been identified in patients with PA. Most of the mutations cause increased intracellular calcium (Ca2+) levels, resulting in activated CYP11B2 transcription and elevation of aldosterone production. These somatic mutations have also been observed in APCC in normal adrenal glands. Recent histopathologic studies demonstrated that older age is associated with greater adrenal APCC content and a concomitant biochemical phenotype that supports progressive autonomous aldosteronism. These findings provide a possible link between age-related histological changes in adrenal CYP11B2 expression and age-related physiological changes in aldosterone secretion. In this review, we cover recent topics on physiology and dysregulation of aldosterone production and discuss potential age-related effects on the aldosterone and adrenal physiology.
