Trilostane and the normal hypothalamic-pituitary-adrenocortical axis

Trilostane has been used to treat Cushing's syndrome and other adrenocortical disorders. To investigate its effect on the normal adrenal gland, trilostane (initially 240 mg/day) was given to ten healthy men, the dose increasing at weekly intervals by 240 mg/day up to a final dose of 960 mg/day. The drug was well tolerated although one subject withdrew after the first week because of gastrointestinal side effects. Trilostane had no significant effect on aldosterone levels or blood pressure. The mean 24-h urinary free cortisol excretion rose from 14.2 to 22.0 mumol/mol creatinine (P less than 0.01) before and after trilostane 240 mg/day but did not rise thereafter. Early morning serum cortisol and plasma ACTH levels did not change on trilostane. The mean increment in serum cortisol after the i.v. injection of 0.25 mg of ACTH was reduced from 398 nmol/l before trilostane to 287 nmol/l on 240 mg/day and to 291 nmol/l on 960 mg/day (P less than 0.01). Insulin-induced hypoglycaemia while on 960 mg/day produced a maximum increment in serum cortisol of 361 +/- 118 nmol/l (mean +/- SD) although one subject had a subnormal increment of 180 nmol/l (normal greater than 200 nmol/l). Plasma ACTH rose with hypoglycaemia in all cases. We conclude that trilostane has only a minor effect on the normal hypothalamic-pituitary-adrenocortical axis.