The Influences of ACTH, Dietary Sodium, Upright Posture and Angiotensin II on Plasma 18-Hydroxy-11-Deoxycorticosterone Levels in Normal Subjects

Abstract

18-Hydroxy-11-deoxycorticosterone (18-OH-DOC), a normal secretory product of the human adrenal cortex, has been found to be elevated in certain forms of experimental and human hypertension. However, normal plasma levels and the acute regulatory factors for 18-OH-DOC secretion in man have not been well documented. To measure 18-OH-DOC levels in man, a specific and sensitive radio-immunoassay procedure was developed. ACTH infusion (Cortrosyn® 0.25 mg × 4 h) produced an 18–20-fold increase in mean 18-OH-DOC levels (5.8 ± 0.8 to 112 ± 12 ng %). After dexamethasone (2 mg p.o. × 2 days) mean levels fell to 0.6 ± 0.1 ng %. Diurnal variation studies under normal activity showed that 0800 h 18-OH-DOC levels (9.9 ± 1.5 ng %) fell by 60% (4.0 ± 0.8 ng %) at 1100 h and by 83% (2.7 ± 0.2 ng %) at 2300 h. To compare the relative responsiveness of 18-OH-DOC to plasma cortisol (F) and aldosterone (aldo), graded low dose infusions of ACTH (12.5-200 mIU/30 min) were performed in 6 subjects. At all infusion rates of ACTH, 18-OH-DOC demonstrated a relatively greater response than plasma F or aldo. The role of volume and sodium in 18-OH-DOC regulation was also examined. Angiotensin II infusion in 6 subjects resulted in a significantly greater (P < 0.05) 18-OH-DOC level (13.7 ± 2.2 ng %) at 120 min compared to baseline (6.0 ± 2.2 ng %) or 30 min postinfusion (7.2 ± 2.4 ng %). After 5 days of low sodium diet (10 mEq), the 1100 h upright 18-OH-DOC value (9.4 ± 1.5 ng %) was significantly higher than the 1100 h level (4.2 ± 0.8 ng %) on high sodium intake. Also, the 0800 h upright value (9.2 ± 1.5 ng %) was higher than 0800 h supine levels (5.6 ± 0.8 ng %). There were no significant changes in 18-OH-DOC after saline infusion or 9α-fluorohydrocortisone administration. We conclude that 18-OH-DOC exhibits marked sensitivity to small changes in ACTH indicating this is the predominant control factor. However, dietary sodium restriction and upright posture also increase 18-OH-DOC levels. The increments in 18-OH-DOC during angiotensin II infusion suggest that changes in the renin-angiotensin system may mediate the response of 18-OH-DOC to sodium and posture changes.