Peripheral clock system circadian abnormalities in Cushing's disease.

In Cushing's syndrome, the cortisol rhythm is impaired and can be associated with the disruption in the rhythmic expression of clock genes. In this study, we evaluated the expression of genes in peripheral blood leukocytes of healthy individuals (n = 13) and Cushing's disease (CD) patients (n = 12). Participants underwent salivary cortisol measurement at 0900 h and 2300 h. Peripheral blood samples were obtained at 0900 h, 1300 h, 1700 h, and 2300 h for assessing clock gene expression by qPCR. Gene expression circadian variations were evaluated by the Cosinor method. In healthy controls, a circadian variation in the expression of , and was observed, whereas the expression of and followed no specific pattern. The expression of and in healthy leukocytes presented a late afternoon acrophase, similarly to , whereas showed night acrophase, similarly to . In CD patients, the circadian variation in the expression of clock genes was lost, along with the abolition of cortisol circadian rhythm. However, exhibited a circadian variation with acrophase during the dark phase in patients. In conclusion, our data suggest that Cushing's disease, which is characterized by hypercortisolism, is associated with abnormalities in the circadian pattern of clock genes. Higher expression of at night outlines its putative role in the cortisol circadian rhythm disruption.