Most
adrenocortical carcinomas (ACCs) produce excessive amounts of
steroid hormones including
aldosterone,
cortisol, and
steroid precursors. However,
aldosterone- and
cortisol-producing cells in ACCs have not yet been immunohistochemically described. We present a case of ACC causing mild primary
aldosteronism and subclinical
Cushing's syndrome. Removal of the
tumor cured both conditions. In order to examine the expression patterns of the steroidogenic
enzymes responsible for adrenocortical
hormone production, 10
tumor portions were immunohistochemically analyzed for
aldosterone synthase (
CYP11B2), 11β-hydroxylase (
CYP11B1,
cortisol-synthesizing
enzyme), 3β-hydroxysteroid
dehydrogenase (3βHSD, upstream
enzyme for both
CYP11B2 and
CYP11B1), and 17α-
hydroxylase/C17-20
lyase (
CYP17, upstream
enzyme for
CYP11B1, but not for
CYP11B1).
CYP11B2,
CYP11B1, and 3βHSD were expressed sporadically, and their expression patterns varied significantly among the different
tumor portions examined. The expression of these
enzymes was random and not associated with each other.
CYP17 was expressed throughout the
tumor, even in CYP11B2-positive cells. Small
tumor cell populations were
aldosterone- or
cortisol-producing cells, as judged by 3βHSD coinciding with either
CYP11B2 or
CYP11B1, respectively. These results suggest that the
tumor produced limited amounts of
aldosterone and
cortisol due to the lack of the coordinated expression of steroidogenic
enzymes, which led to mild clinical expression in this case. We delineated the expression patterns of steroidogenic
enzymes in ACC. The coordinated expression of steroidogenic
enzymes in normal and
adenoma cells was disturbed in ACC cells, resulting in the inefficient production of
steroid hormones in relation to the large
tumor volume.