Dynamics of adrenocorticotropin (ACTH) secretion in cyclic Cushing's syndrome: evidence for more than one abnormal ACTH biorhythm.

We have studied a 57-yr-old woman with cyclic Cushing's syndrome of apparent pituitary origin who had a predominant cycle of 2-6 days. The patient also demonstrated an abnormal circadian rhythm, with afternoon peaks of plasma ACTH and plasma cortisol. In addition to these abnormal biorhythms, Fourier analysis showed what appeared to be a separate 35-day cycle. After 35 days of consecutive urinary free cortisol measurement, the patient was given cyproheptadine. During therapy with this agent, the urinary free cortisol levels fell dramatically, but cyclic secretion continued, albeit with a diminished amplitude. During general anesthesia for a bilateral adrenalectomy, there was a striking increase in the plasma ACTH level, and the ACTH concentration remained high in both the immediate and late postoperative periods. These observations indicated that stress could overcome cyclic ACTH secretion and that cortisol exerted feedback suppression on ACTH secretion. Although this is the predictable response for classic pituitary-dependent Cushing's syndrome, it is of interest in cyclic Cushing's syndrome, since previous studies of this entity have implied that cortisol secretion is independent of stimulation or feedback.