Cushing's syndrome with a paradoxical response to dexamethasone.

Abstract

Abstract A paradoxical response to dexamethasone was observed in a patient with Cushing's syndrome due to bilateral adrenal hyperplasia. Postoperatively the patient died and was found to have a basophil adenoma of the pituitary. In two separate tests the administration of dexamethasone caused increases in urinary 17-hydroxysteroids and 17-ketosteroids. After the administration of dexamethasone, plasma ACTH activity appeared slightly increased and urinary 17-hydroxysteroid metabolites were similar to those found after the administration of ACTH. Metyrapone caused an initial rise in urinary 17-hydroxysteroids due to an increase in tetrahydro-11-deoxycortisol, as would be expected, but a much larger increase in adrenal corticoid excretion occurred on the second and third days after metyrapone treatment and was associated with the reappearance of urinary cortisol metabolites. Incubation of adrenal slices in the presence of dexamethasone did not stimulate the conversion of labeled acetate to cortisol. These findings implicate the pituitary adenoma in the paradoxical response, and suggest that it was mediated by ACTH. The early response to metyrapone indicates that there was an intact positive feedback mechanism, the late rise in cortisol metabolites suggests that ACTH secretion was also paradoxically stimulated by endogenous adrenal corticoids.