Expression of Steroidogenic Enzyme Messenger Ribonucleic Acids and Corticosteroid Production in Aldosterone-producing and "nonfunctioning" Adrenal Adenomas

"Nonfunctioning" adrenal adenomas are often diagnosed in patients without recognizable clinical symptoms of adrenocortical hyperfunction. The objective of this study was to determine directly the steroidogenic activity of such adenomas (n = 12) and compare them histologically and functionally to normal human adrenals (n = 6) and aldosterone-producing adenomas (n = 15). The histological appearances of nonfunctioning and aldosterone-producing adenomas were surprisingly similar. Nonfunctioning adrenal adenomas expressed all mRNAs of P450scc, P450c17, P450c21, adrenodoxin, and adrenodoxin reductase with relative levels comparable to those found in normal adrenals. Consistent with their hormone-producing nature, these adenomas had cortisol and aldosterone contents as high as those in normal adrenal tissues, a significantly (P < 0.05) increased 17-hydroxyprogesterone content, and a disproportionally low expression of P450c21 mRNA compared to aldosterone-producing adenomas. Cells isolated from both aldosterone-producing and nonfunctioning adrenal adenomas exhibited highly ACTH-sensitive cortisol and aldosterone production, suggesting again the presence of both zona glomerulosa-like and zona fasciculata-like steroidogenesis in these adenoma tissues. These results indicate that so-called nonfunctioning adrenal adenomas are not without steroidogenic activity. Therefore, the assumption that adrenal adenomas are entirely nonfunctioning in the absence of recognizable hormonal hyperfunction may not be correct.