Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome

Abstract

Abstract. A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy. Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF. The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.