Characterization of the twenty-four hour secretion patterns of adrenocorticotropin and cortisol in normal women and patients with Cushing's disease.

The episodic and circadian secretory patterns of ACTH and cortisol were studied in five patients with Cushing's disease (CD) and nine normal women by repetitive (every 20 min) venous blood sampling. In contrast to normal women, the 24-h transverse mean plasma ACTH levels were more than 3-fold greater (P less than 0.01), and the 24-h transverse mean serum cortisol levels were more than 2-fold higher (P less than 0.001) in the CD patients. Using a pulse detection algorithm, we found that the elevated ACTH levels in CD were accounted for, in part, by the more than 2-fold greater elevation in mean pulsatile ACTH amplitude (P less than 0.01), while the mean frequency of episodic ACTH and cortisol secretion was similar to that in normal subjects (10-12 episodes/24 h). Although a relatively close temporal relationship between ACTH and cortisol secretory episodes was found (r = 0.70 and 0.72, normal and CD groups, respectively), the increased ACTH pulse amplitude was not consistently associated with comparable cortisol pulses in CD patients. Circadian rhythms were identified for ACTH in two CD patients and for cortisol in all CD patients. The timing of the acrophases and nadirs for cortisol was not significantly altered compared to that in the normal group. After the noon meal, the normal postprandial elevation in cortisol was depressed or absent in the CD group. ACTH and cortisol responses to CRH in four CD patients were highly variable, but were not significantly different from those in normal subjects. These studies demonstrate that the elevated plasma ACTH levels in CD are sustained in part by increased ACTH pulse amplitude without significant alterations in pulse frequency. Despite the persistently high ACTH levels, the circadian variation of cortisol is maintained. The finding of an abnormal postprandial cortisol response in CD may provide an additional biological marker for CD.