Concomitant falls of plasma cortisol and ACTH levels in a case of Cushing's disease during treatment with trilostane

A 72-year-old man with Cushing's disease was treated with trilostane, a competitive inhibitor of adrenal 3β-hydroxysteroid dehydrogenase (3β-HSDH). The treatment with trilostane successfully lowered urinary excretion of 17-hydroxycorticosteroids (17-OHCS) and plasma levels of cortisol and elevated the plasma level of dehydroepiandrosterone. Unexpectedly, plasma ACTH fell from 109.7 ± 45.0 to 42.7 ± 27.3 pg/ml (P < 0.01) in parallel with plasma cortisol. The hyperresponsiveness of plasma ACTH observed both in the metyrapone test and the lysine-vasopressin test was also ameliorated by treatment with trilostane. Then low dose of pituitary irradiation with cobalt-60 was added and his urinary excretion of 17-OHCS and plasma levels of cortisol decreased further. After treatment with trilostane was finally stopped, the plasma ACTH increased from 45.9 ± 21.9 to 69.6 ± 25.3 pg/ml (P < 0.05) in parallel with plasma cortisol. Since then he has had no recurrence for 12 months. These observations suggest that trilostane, like other adrenal enzyme-inhibiting drugs, may induce unexpected improvement of the abnormality of the hypothalamic-pituitary axis present in Cushing's disease.