Cushing's syndrome is associated with an advanced chronotype

Cushing's syndrome is characterised by chronic glucocorticoid excess that abolishes the physiological circadian cortisol rhythm. We investigated whether this circadian disruption alters chronotype. In a single-centre case-control study, chronotype was assessed using the Munich ChronoType Questionnaire (MCTQ; n = 119) and wrist actigraphy (n = 39) in patients with active Cushing's syndrome, patients in biochemical remission, and healthy controls. The primary outcome was mid-sleep on free days corrected for sleep debt (MSFsc). Multivariable analysis was performed to identify independent predictors of chronotype. Agreement between methods was assessed by Bland-Altman analysis. Patients with active Cushing's syndrome had a significantly earlier chronotype than patients in remission and controls (MSFsc by MCTQ: 2.38 h [IQR 1.22; 3.41] vs. 3.29 h [IQR 2.65; 4.32] vs. 3.73 h [IQR 3.16; 4.08]; p = .007 and p = .0003, respectively; actigraphy: 3.15 ± 0.90 h vs. 4.03 ± 0.96 h vs. 4.46 ± 0.75 h; p = .039 and p = .001, respectively). Chronotype did not differ significantly between patients in remission and controls. In a multivariable quantile regression model, active Cushing's syndrome was an independent predictor of chronotype (1.32 h earlier than controls; p = .049), while age, BMI, psychiatric symptoms and sleep disturbance had no significant influence. Actigraphy confirmed earlier sleep offset and acrophase in active Cushing's syndrome. MCTQ and actigraphy were significantly correlated (Pearson r = 0.619, p = .0003, n = 29); agreement analysis revealed no systematic bias, but a significant proportional bias, reflecting wider dispersion of MCTQ-derived values. Patients with active Cushing's syndrome have an earlier chronotype than patients in remission and healthy controls, as determined by both subjective and objective methods. Chronotype assessment, particularly with the MCTQ, may complement biochemical monitoring.