To evaluate circulating irisin levels in patients with active and controlled Cushing's disease (CD).Forty-four patients with CD evaluated during the active phase and after 12 months of biochemical remission and 40 controls were recruited.Phenotypic, anthropometric, hormonal and metabolic parameters, including insulin sensitivity estimation by homeostatic model of insulin resistance, Matsuda index and oral disposition index and circulating irisin levels were evaluated.Patients with active CD showed lower irisin levels compared to controls (p<0.001) and controlled CD (p<0.001). The independent variables significantly associated with irisin were waist circumference (WC) (p=0.025), body fat percentage (BF%) (p=0.009), PTH (p=0.007) and chair rising test (CRT) (p<0.001) in active CD and WC (p=0.013), BF% (p=0.014), PTH (p=0.038), CRT (p=0.029) and urinary-free cortisol (p<0.001) in controlled CD.Circulating irisin levels tend to be lower in patients with active CD compared to those with controlled CD and controls. They are strongly associated with osteosarcopenia and central obesity in CD and therefore may be a possible marker of diagnosis.