CHANGES OF THE ZONA GLOMERULOSA IN HUMAN ADRENALS FROM BIRTH TO 40 YEARS OF AGE

Abstract

Objective: Antibodies to CYP11B2 (aldosterone synthase) allow imaging of the zona glomerulosa (zG) by immunohistochemistry. Studies demonstrate that the area and continuity of the zG decreases with aging and accumulations of aldosterone-producing cell clusters occur. Research on age-related changes in the zG in younger patients and comparison of both adrenals is limited. Therefore, the objective of this study was to elucidate age-related changes of the zG by quantifying CYP11B2 expression in adrenals of patients below the age of 40 years. Design and method: We collected human adrenals from autopsy cases, that were anonymized except for age, sex and medical history. We excluded adrenal glands of patients with premature birth, hypertension, cardiovascular disease, adrenal tumors, use of steroids. In case of two available adrenals in one patient, one was randomly selected of the two. We validated software for automated quantification by comparing manually outlined CYP11B2 expressing area with automated outlined area. We then used this automated method to quantify CYP11B2 expressing area, CYP11B2 continuity and mean and maximum CYP11B2 depth. If the zG was discontinuous, mean length of ‘gaps’ between ZG tissue was calculated. We also determined the structural similarity between both adrenals of the same case. The study was approved by the local Medical Ethics Committee. Results: There was a negative correlation between age and CYP11B2 expressing area (rs = -.63); negative correlation between age and CYP11B2 continuity (rs = -.80); positive correlation with age and mean gap length (rs = 0.71); positive correlation between age and maximum CYP11B2 depth (rs = .30, P = <0.001) and no correlation between age and mean CYP11B2 depth (rs = .01, p = <0.001). The intraclass correlation coefficient between both adrenals of one subject for CYP11B2 expressing area was 0.78 (95%CI = 0.56–0.89), for CYP11B2 continuity 0.94 (95%CI = 0.88–0.97) and for mean gap length 0.76 (95%CI = 0.32–0.81). Conclusions: We demonstrate a decrease in CYP11B2 area and continuity, whilst the mean gap length and maximum CYP11B2 depth increases, which we consider as involution and clustering of the zG. This is seen in both adrenals and therefore suggests a common process. The relation with the development of aldosterone-producing adenoma remains to be determined.