Cushing's Disease with Periodic Hormonogenesis: One Explanation for Paradoxical Response to Dexamethasone

Abstract

A patient with Cushing's disease who exhibited a “paradoxical response to dexamethasone” was studied in detail over a period of 100 days in an effort to determine the basis of her unusual response to attempted pituitaryadrenal suppression. In the course of the study it became apparent that her pituitary-adrenal overactivity was spontaneously rhythmic, with cycles occurring approximately every 11 days, and that the apparent paradoxical response to dexamethasone had been purely fortuitous. Urinary 17-hydroxycorticosteroids at the peaks of the cycles averaged 125 mg per day and, at the nadirs, 18 mg per day. The cycles were not altered by treatment with dexamethasone, metyrapone, cortisol, or L-dopa. During the interval between spontaneous peaks, adrenal responsiveness to exogenous ACTH and pituitary–adrenal responsiveness to exogenous vasopressin were demonstrable, thus excluding cyclic exhaustion of pituitary or adrenal reserve as an explanation for the periodic hormonogenesis.The patient's hypercortisolism disappeared following removal of a chromophobe adenoma.It is recommended that all patients with “paradoxical responses to dexamethasone” be subjected to further study to ascertain whether there are spontaneous periodic variations in cortisol secretion having no more than a coincidental relationship to the administration of dexamethasone.