Virilizing adrenocortical adenoma: in vitro steroidogenesis, immunohistochemical studies of steroidogenic enzymes, and gene expression of corticotropin receptor.

Background: No reports have yet precisely determined corticotropin (ACTH) responsiveness in virilizing adrenocortical adenoma.
Methods: Five women with an androgen-secreting adrenal adenoma were reviewed. Three of them were examined by in vitro steroidogenesis. Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis.
Results: In preoperative hormonal determinations plasma and urine androgens had increased. Dexamethasone did not suppress plasma and urinary androgens, nor did ACTH increase them. In vitro steroidogenesis revealed that the adenoma cells produced mainly dehydroepiandrosterone and a small amount of testosterone. ACTH did not increase the in vitro production of androgens. In immunohistochemical staining 5 enzymes involved in adrenal steroidogenesis were all expressed, especially 17 alpha-hydroxylase, which was strongly expressed in tumor cells. ACTH receptor messenger RNA was not detected in virilizing tumor tissues, whereas it was expressed in attached adrenal tissues.
Conclusions: The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells. Androgens were autonomously produced in adrenal adenoma cells without ACTH regulation.