Background and study aims: Increased aldosterone production in the adrenal gland plays a role in many hypertensive patients. Structural changes of the zona glomerulosa with age in normotensive patients have been described in literature but the influence of aging on aldosterone secretion and physiology is unclear. The aim of this study is to investigate changes in the ZG in order to gain insight in the origin, development and definition of aldosterone producing cell clusters (APCCs) in the normal aging adrenal in patients aged 0 to 40 years old.
Material and methods: We studied one or both adrenal glands collected at autopsies of normotensive patients aged 0 to 40 years who died of non-adrenal disease. We divided patients in age groups 05 years, 610 years, 1118 years, 1930 years and 3140 years. We related aldosterone synthase (CYP11B2) expression, assessed by immunohistochemistry, with age.
Results: Eighty seven adrenal glands from 58 normotensive patients were collected and classified according to age group. All adrenal glands of patients aged 0 to 10 years show a continuous pattern of aldosterone producing cells without clustering in the outer layer of the adrenal cortex (zona glomerulosa), see Figure 1. In adolescence a discontinuous pattern arises and aldosterone-producing cells start to form clusters (APCCs). With increasing age the number of APCCs then increases. In cases where both adrenal glands of an individual were available (n=29) the CYP11B2 expression was symmetric.
Conclusion and discussion: The pattern of CYP11B2 expression in the adrenal cortex evolves over time, and this change can be described as an increase in APCC number with disruption of the continuity of the zona glomerulosa. However, we encountered the problem that a clear definition of APCCs is lacking, rendering quantification of volume and number of APCCs difficult. We nevertheless hypothesize that changes in aldosterone production patterns, exemplified by emergence of APCCs and rarefaction of the zona glomerulosa, may play a causative role in the development of both resistant hypertension and primary aldosteronism.
Figure 1 Relationship between CYP11B2 expression patterns and age in normal adrenals. Findings of CYP11B2 immunohistochemistry. CYP11B2-expression is brown. Scale bars in A + C are 2000 μm and scale bars in B + D are 200 μm. A adrenal gland of a 6-year-old boy showing continous CYP11B2 expression with no clustering. B magnification of the boxed area in A. C. adrenal gland of a 39-year-old women showing a discontinuous CYP11B2 expression with a lot of cell clusters. D magnification of the boxed area in C.
18 May 2019 - 21 May 2019