Effects of Triparanol on the Secretion and Metabolism of Adrenal Corticosteroids

Abstract

Although triparanol has been shown previously to cause a decrease in urinary 17-hydroxycorticosteroids (17-OHCS) in normal subjects and in patients with Cushing's syndrome, the underlying mechanism has not been established. The present study indicates that triparanol decreases the urinary 17-OHCS by modifying the extra-adrenal metabolism of cortisol. The fall in the urinary 17-OHCS produced by triparanol is not accompanied by a decrease in the plasma 17-OHCS nor by a decrease in the cortisol secretion rate. In addisonian patients maintained on constant doses of exogenous cortisol, triparanol reduces the urinary 17-OHCS to approximately the same degree as in subjects with intact adrenal function. Triparanol does not significantly increase the degree of binding of cortisol by plasma proteins, but it does cause a slight prolongation of the rate of disappearance of tracer doses of 4-C¹⁴-cortisol from the plasma of normal subjects. Triparanol has no effect upon the rate of aldosterone secretion nor upon the rate of sodium excretion by subjects maintained on constant sodium intake. In dogs with chronic adrenal vein cannulae, the drug does not decrease the adrenal venous 17-OHCS. In rats, triparanol does not impair the adrenal secretion of corticosterone in response to ACTH.