Trilostane and the normal hypothalamic-pituitary-adrenocortical axis.

Area of Science:

• Endocrinology
• Pharmacology

Background:

• Trilostane is a medication prescribed for adrenocortical disorders like Cushing's syndrome.
• Its effects on the normal adrenal gland require thorough investigation.

Purpose of the Study:

• To evaluate the impact of escalating doses of trilostane on the healthy human adrenal gland and the hypothalamic-pituitary-adrenocortical (HPA) axis.
• To assess the drug's safety and tolerability in healthy male volunteers.

Main Methods:

• Ten healthy men received escalating doses of trilostane, starting at 240 mg/day and increasing weekly to 960 mg/day.
• Measurements included 24-hour urinary free cortisol, early morning serum cortisol, plasma ACTH, aldosterone levels, and blood pressure.
• Adrenal responsiveness was tested using ACTH stimulation and insulin-induced hypoglycemia.

Main Results:

• Trilostane was generally well-tolerated, with one participant discontinuing due to gastrointestinal issues.
• No significant changes were observed in aldosterone levels or blood pressure.
• A significant increase in 24-hour urinary free cortisol was noted at 240 mg/day but not at higher doses.
• The cortisol response to ACTH stimulation was significantly blunted at both 240 mg/day and 960 mg/day.
• Insulin-induced hypoglycemia provoked a cortisol increment, though one subject showed a subnormal response.

Conclusions:

• Trilostane exhibits a minor effect on the normal hypothalamic-pituitary-adrenocortical axis in healthy men.
• The drug's impact on cortisol regulation is dose-dependent and limited at therapeutic levels.
• Further research may be warranted to fully elucidate the long-term effects and safety profile.