Urinary 18-hydroxycortisol and its relationship to the excretion of other adrenal steroids

Abstract

The urinary excretion of 18-hydroxycortisol was recently reported to be increased in patients with primary aldosteronism who have an adrenal adenoma and in those with glucocorticoid-suppressible aldosteronism. A direct RIA for 18-hydroxycortisol in urine and plasma has been described, and we here report our experience using a similar direct RIA and a more elaborate RIA which includes a preliminary high pressure liquid chromatography (HPLC) purification step. The urinary excretion of 18-hydroxycortisol was compared with that of other adrencorticoids. The urinary excretion of 18-hydroxycortisol in 37 normal subjects using the direct RIA was 112 +/- 49 (+/- SD) microgram/24 h, and that with the HPLC-RIA method was 63 +/- 36 micrograms/24 h. The accuracy and specificity of the HPLC-RIA assay method were confirmed by measuring the steroid after the HPLC step as the glycolic acid ester derivative. The urinary excretion of 18-hydroxycortisol correlated with that of cortisol (r = 0.36; P less than 0.01), 18-oxocortisol (r = 0.42; P less than 0.01), and 19-nordeoxycortisosterone (r = 0.71; P less than 0.001), but did not correlate with the excretion of aldosterone 18-oxoglucuronide (r = 0.25; P = 0.15942). Dexamethasone administration to five normal subjects significantly decreased 18-hydroxycortisol excretion from 81 +/- 47 to 23 +/- 8 micrograms/24 h. ACTH infusion in these subjects receiving dexamethasone significantly raised 18-hydroxycortisol excretion to 147 +/- 37 micrograms/24 h. Five days of a sodium-restricted diet (10 mmoles/day) resulted in a significant (P less than 0.02) increase in 18-hydroxycortisol excretion, but two of eight subjects had decreased excretion, although urinary aldosterone excretion increased, as expected. These studies demonstrate that the direct RIA significantly overestimates urinary 18-hydroxycortisol excretion. These studies also demonstrate that the major factor resulting 18-hydroxycortisol excretion is ACTH. However, since 18-hydroxycortisol excretion may increase during sodium depletion, angiotensin or other factors may also regulate its secretion.