The inhibiting effect of trilostane on adrenal steroid synthesis: hormonal and morphological alterations induced by subchronic trilostane treatment in normal rats

In adult male rats the effect of a subchronic treatment with trilostane, a new, orally active, competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, on adrenal steroid production and morphology was studied. Rats were treated with 150 mg or 300 mg trilostane/kg/day for 7 or 14 days and with 150 mg trilostane/kg/day for 10 days in combination with 75 mg propranolol/kg/day or 1 mg indomethacin/kg/day. Trilostane leads to a dose-dependent increase in adrenal weight and to a rather uniform increase in nuclear volumes of zona glomerulosa and zona fasciculata cells. The basal secretion of aldosterone and corticosterone is not significantly altered. Trilostane increases the excretion of sodium and potassium in urine. The stimulating effect of trilostane on plasma renin activity and the adrenal enlargement are not inhibited by propranolol or indomethacin. We conclude that trilostane induces latent adrenal insufficiency. Increased renin and ACTH maintain normal basal steroid levels, and might impair the therapeutic effectiveness of trilostane.