Aldosterone-Producing Adenoma: Does a Larger Tumor Secrete More Apparent Cortisol?

Previous studies revealed that aldosterone-producing adenoma(APA) had a potential for excess co-secretion of cortisol. APA was considered to be composed of heterozygous cell types, including cortisol producing cells(expression of CYP11B1) and aldosterone-producing cells(expression of CYP11B2). The proportion of two cell types and the expression of two steroid synthases showed great heterogeneity in APAs, which may lead to differences in cortisol secretion. However, the hypothesis has not been tested. Therefore, we examined the correlation between tumor size and the ability to autonomously secrete cortisol of APA from the perspective of steroid hormones and immunohistochemistry. 165 patients with surgically proven APA were retrospectively studied. Patients with apparent excess cortisol co-secretion were excluded, which was confirmed by an overnight 1 mg dexamethasone suppression test(1mg-DST). Immunohistochemical staining was performed in 88 tumor specimens and CYP11B2-negative APAs were excluded. The expression of the steroidogenic enzymes was immunohistochemically analyzed, and semi-quantified according to the McCarty H-score system. All APA cases were classified into 2 groups according to the median(15mm) of maximum diameter detected by histological examination: the smaller(n=102) and larger group(n=63). 24am cortisol[78.7(47.7–121.5) VS. 54.6(33.6–81.4) nmol/l, p =0.002] and cortisol after 1mg-DST[28.8(19.1–40.9) VS. 24.1(16.8–30.7) nmol/l, p =0.024] were significantly higher in the larger APA group. The larger APA group had a higher H score of CYP11B1 (p=0.028) and a lower H score of CYP11B2 (p=0.036). Both 24pm cortisol (r =0.2424, p =0.0058)and cortisol after 1mg-DST(r =0.2476, p =0.042)were positively correlated with tumor diameter. The tumor diameter was positively correlated with the H score of CYP11B1 (p=0.0328) and inversely with the H score of CYP11B2(p=0.0285). We tentatively used a new ratio B1 index, calculated by H score of CYP11B1 divided by the sum of H score of CYP11B2 and CYP11B1, to represent the relative expression intensity of CYP11B1 in tumor specimens. B1 index had a stronger correlation with tumor diameter (r =0.3134,p=0.0041). Cortisol after 1mg-DST increased linearly with the tertiles of tumor diameter(p for trend<0.0001). These results suggested that APA without clinically overt cortisol secretion might have a higher proportion of cells expressing CYP11B1 to produce more cortisol with the increasing of tumor size, even developing to overt Cushing syndrome.