The combined use of sodium valproate and metyrapone in the treatment of Cushing's syndrome.

We have investigated the combined use of metyrapone and sodium valproate in the treatment of five cases of dexamethasone-suppressible Cushing's disease and one case with dexamethasone non-suppressible disease. Metyrapone alone reduced 24 h urinary free cortisol (UFC) and plasma cortisol concentrations. Addition of sodium valproate to metyrapone produced a further reduction in these values in five of six patients with a reduction in plasma ACTH in three of five patients who had dexamethasone-suppressible disease. Plasma 11-deoxycortisol increased markedly on metyrapone. However, addition of valproate produced a further rise in 11-deoxycortisol values in four of five patients including the patient with dexamethasone non-suppressible disease. The results suggest that valproate may be a useful addition to metyrapone in the medical treatment of some patients with Cushing's syndrome and that it may have an action both at the hypothalamus and peripherally.