Although organization and hormonal regulation of the hypothalamic-pituitary-adrenocortical (HPA) and the hypothalamic-pituitary-thyroid (HPT) axes share a remarkable degree of similarities, distinctive patterns of their plasma hormone secretions are observed. We measured plasma levels of ACTH-cortisol (PA) and hTSH-T3 (PT) pairs of hormones in 24-hour sequential blood specimens sampled at 30-minute intervals from 3 patients with suspected adrenal disorders and 4 normal volunteers and found the same percentage of discordant secretions of the PA and PT hormones but significantly greater coefficients of variations of the PA values than the PT values (p < 0.002). This confirms that plasma PT hormones are more tightly self-regulated between themselves than plasma PA hormones. Moreover, cluster analysis of the 24-hour plasma hormonal fluctuations revealed one or more ACTH-cortisol hyposecretory clusters only in subjects with a normal status of adrenal function. There was no similar hTSH-T3 hyposecretory cluster detected in any one of the 7 subjects. Based on these results, we postulate that there is some adrenal factor normally exerting a subtle antagonistic action against ACTH and causes the incidence of such ACTH-cortisol hyposecretory cluster.