Secretion of 6β-hydroxycortisol by normal human adrenals and adrenocortical adenomas

Abstract

Although 6β-hydroxycortisol (6βOHF) is usually considered a cortisol metabolite produced by the liver, a few reports suggest that it may also originate from extrahepatic sources. To examine whether human adrenal cells are capable of 6β-hydroxylating cortisol, we measured 6βOHF secretion with a radioimmunoassay method in isolated human adrenal cell systems obtained from three normal adrenals, four nonhyperfunctioning adrenocortical adenomas, two adrenal adenomas causing Cushing’s syndrome, and five aldosterone (Aldo)-producing adenomas. Cells were examined both under basal conditions and after stimulation with adrenocorticotrophic hormone (ACTH). In addition, 6βOHF concentrations were determined in inferior vena cava and suprarenal vein plasma samples obtained from the side of nonhyperfunctioning adrenal adenomas (five patients) and aldosterone-producing adenomas (five patients). Under basal incubation conditions, 6βOHF secretion, expressed as a percent of cortisol secretion, was between 0.5 and 2.0% in normal adrenal cells, between 1.0 and 7% in cells from nonhyperfunctioning adenomas, 12 and 15% in cells from Cushing’s syndrome patients, and between 2.6 and 3.9% in cells from aldosterone-producing adenomas. In these cells, increasing doses of ACTH produced a dose-dependent stimulation of both 6βOHF and cortisol secretion. The 6βOHF concentration in suprarenal vein samples obtained from the side of adenomas was markedly increased; the suprarenal vein/inferior vena cava 6βOHF ratios were 13.1±2.1 (mean±S.E.) in the case of nonhyperfunctioning adenomas and 17.8±4.5 in the case of aldosterone-producing adenomas. These results firmly suggest that 6βOHF is not only a hepatic metabolite, but also a secretory product of human adrenals and that similarly to cortisol, its secretion may be controlled by ACTH.