Immunohistochemical analysis of steroidogenic
enzymes (P-450 side-chain cleavage,
3 beta-hydroxysteroid dehydrogenase, P-450
C21-
hydroxylase, P-450
17 alpha-hydroxylase and P-450
11 beta-hydroxylase) was performed on fifteen cases of small
adrenocortical adenomas, which were detected incidentally in hormonally asymptomatic patients (non-functioning adrenocortical
tumor), in order to study steroidogenesis in these
tumors. Immunolocalization revealed that all cases examined expressed all the
enzymes in the adrenocortical steroidogenic pathway to various degrees, and in twelve cases abnormalities of precursor
hormones and
steroid metabolites were clinically observed. Attached non-neoplastic adrenals were present in twelve cases. Among these twelve cases, eight showed cortical
atrophy, especially in the zona fasciculata. These atrophied adrenals expressed little immunoreactivity of the
enzymes examined. These results strongly indicate that most of small non-functioning adrenocortical
tumors have the capacity to produce biologically active
steroids including
cortisol, although not necessarily associated with
hypercorticism. Especially in the cases with cortical
atrophy in attached non-neoplastic adrenals, it is considered that autonomous neoplastic production and secretion of
cortisol may be insufficient to cause clinical and routine laboratory abnormalities but sufficient to subtly alter the hypothalamic-pituitary-adrenal axis by suppressing
ACTH and/or CRF secretion and to result in adrenocortical
atrophy. It should be recognized that corticosteroidogenesis does take place in the majority of clinically small non-functioning adrenocortical
tumors incidentally detected in hormonally asymptomatic patients when managing these patients.