Evaluation of the Eflficiency of 11β-Hydroxylation of 11-Deoxycortisol in Human Subjects1

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Abstract
The efficiency of the hydroxylation of 11-deoxycortisol to cortisol in the human adrenal cortex was evaluated indirectly in vivo by measuring 11-deoxycortisol and cortisol secretion rates, using as a parameter the ratio 100 F/F +S, F+S being the cortisol and 11-deoxycortisol secretion rates. Under basal conditions hydroxylation is very efficient, 11-deoxycortisol secretion representing only ±4% of total cortisol and 11-deoxycortisol secretion; whereas ACTH stimulation does not significantly decrease this efficiency, the former decreases rapidly with increasing doses of Metopiron, 11-deoxycortisol secretion rates increasing enormously even with doses as low as 1 g of Metopiron/day. Although at identical doses of Metopiron 11-heoxycortisol secretion is very variable, the decrease of efficiency (or inhibition) of the 11β-hydroxylase is relatively constant. In patients treated with estrogens and in the patient treated with 6α-methyl-17-acetoxyprogesterone, however, Metopiron produces a much smaller decrease in the efficiency of the 11-hydroxylase. Taking into account the degree of inhibition obtained, the increase in 11-deoxycortisol secretion in these patients, however, is normal, reflecting a normal pituitary reactivity. It is concluded that, whenever a more exact evaluation of the pituitary reactivity is desired, it is necessary to evaluate the intensity of the stimulus applied, i.e., the degree of inhibition of 11β-hydroxylation, by measuring simultaneously cortisol and 11-deoxycortisol secretion.