Kinetics of plasma corticosteroids during metyrapone infusion in man

The effect of metyrapone on plasma kinetics of cortisol (F), 11-deoxycortisol (S), corticosterone (B), 11-deoxycorticosterone (DOC), aldosterone (Aldo) and 17 hydroxyprogesterone (17 OHP) was studied in ten normal prepubertal children intravenously infused with the drug (1 gm/1.73 m2 body surface area in 4 h). Similar falls in F, B and Aldo were observed during the first hour expressing similar sensitivity of the 11 hydroxylases to the drug. The effect of the compensatory increase of endogenous ACTH could be detected after 1 hour by the rise in 17 OHP. However the concentrations of the 11-hydroxy compounds, F, B and Aldo, remained low throughout the infusion period. From the second hour onwards, facilitation of the synthesis of DOC was noticed. After the end of infusion, the levels of the precursors decreased and F and B were restored to initial values. Aldo remained low probably due to the inhibitory effect of the elevated DOC on the renin-angiotensin system.