THE COMBINED USE OF SODIUM VALPROATE AND METYRAPONE IN THE TREATMENT OF CUSHING'S SYNDROME

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Abstract
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.