Age-Related Autonomous Aldosteronism

Circulation. 2017 Jul 25;136(4):347-355. doi: 10.1161/CIRCULATIONAHA.117.028201. Epub 2017 May 31.


Background: Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and physiology is not well understood.

Methods: The relationship between age and adrenal aldosterone synthase (CYP11B2) expression was evaluated in 127 normal adrenal glands from deceased kidney donors (age, 9 months to 68 years). Following immunohistochemistry, CYP11B2-expressing area and areas of abnormal foci of CYP11B2-expressing cells, called aldosterone-producing cell clusters, were analyzed. In a separate ancillary clinical study of 677 participants without primary aldosteronism, who were studied on both high and restricted sodium diets (age, 18-71 years), we used multivariable linear regression to assess the independent associations between age and renin-angiotensin-aldosterone system physiology.

Results: In adrenal tissue, the total CYP11B2-expressing area was negatively correlated with age (r=-0.431, P<0.0001), whereas the total aldosterone-producing cell cluster area was positively correlated with age (r=0.390, P<0.0001). The integrated ratio of aldosterone-producing cell cluster to CYP11B2-expressing area was most strongly and positively correlated with age (r=0.587, P<0.0001). When participants in the clinical study were maintained on a high sodium balance, renin activity progressively declined with older age, whereas serum and urinary aldosterone did not significantly decline. Correspondingly, the aldosterone-to-renin ratio was positively and independently associated with older age (adjusted β=+5.54 ng/dL per ng/mL per hour per 10 years, P<0.001). In contrast, when participants were assessed under sodium-restricted conditions, physiological stimulation of aldosterone was blunted with older age (β=-4.6 ng/dL per 10 years, P<0.0001).

Conclusions: Aging is associated with a pattern of decreased normal zona glomerulosa CYP11B2 expression and increased aldosterone-producing cell cluster expression. This histopathologic finding parallels an age-related autonomous aldosteronism and abnormal aldosterone physiology that provides 1 potential explanation for age-related cardiovascular risk.

Keywords: aging; aldosterone; aldosterone-producing cell cluster; cytochrome P-450 CYP11B2; primary aldosteronism; renin.

MeSH terms

  • Adolescent
  • Adrenal Glands / metabolism*
  • Adrenal Glands / pathology
  • Adult
  • Age Factors
  • Aged
  • Aging / metabolism*
  • Aging / pathology
  • Child
  • Child, Preschool
  • Cytochrome P-450 CYP11B2 / biosynthesis*
  • Female
  • Humans
  • Hyperaldosteronism / metabolism*
  • Hyperaldosteronism / pathology
  • Infant
  • Male
  • Middle Aged
  • Young Adult


  • Cytochrome P-450 CYP11B2