EFFECT OF 9α-FLUOROHYDROCORTISONE ON THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS

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Abstract
9α-Fluorohydrocortisone (9α-FHC) is used in hypotensive circulatory disorders because of its mineralocorticoid action. In order to determine the influence of this drug on the feedback mechanism of the hypothalamopituitary-adrenal axis, 10 healthy subjects were submitted twice to a shortened metyrapone test before and after the administration of 9α-FHC. The concentrations of 11-oxy- and 11-deoxycorticoids in plasma were measured by a competitive protein binding technique. Following the administration of 9α-FHC the plasma concentrations of 11-deoxycorticoids during the metyrapone tests were lowered considerably (about 52 %; t: 6.08, P < 0.001) compared to the tests under normal conditions. Even pathological test results (total suppression of the hypothalamus by 9α-FHC) were found, demonstrating that 9α-FHC strongly competes with cortisol in the feedback mechanism of the hypothalamopituitary-adrenal axis. In both test series the disappearance half time of 11-oxycorticoid concentrations in the plasma was 28 min, indicating that neither an insufficient nor a delayed decrease in 11-oxycorticoid concentrations is the reason for the low 11-deoxycorticoid plasma concentrations after 9α-FHC. The side effects of metyrapone such as dizziness, confusion and a decrease in blood pressure are not affected by the glucocorticoid dexamethasone or the mineralocorticoid, 9α-FHC.

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