Objective: In patients with active Cushing's syndrome (CS), cardiac structural and functional changes have been described in a limited number of patients. It is unknown whether these changes reverse after successful treatment. We therefore evaluated the changes in cardiac structure and dysfunction after successful treatment of CS, using more sensitive echocardiographic parameters (based on two-dimensional strain imaging) to detect subtle changes in cardiac structure and function. Methods: In a prospective study design, we studied 15 consecutive CS patients and 30 controls (matched for age, sex, body surface area, hypertension, and left ventricular (LV) systolic function). Multidirectional LV strain was evaluated by two-dimensional speckle tracking strain imaging. Systolic (radial thickening, and circumferential and longitudinal shortening) and diastolic (longitudinal strain rate at the isovolumetric relaxation time (SRIVRT)) parameters were measured. Results: At baseline, CS patients had similar LV diameters but had significantly more LV hypertrophy and impaired LV diastolic function, compared to controls. In addition, CS patients showed impaired LV shortening in the circumferential (-16.5 +/- 3.5 vs -19.7 +/- 3.4%, P=0.013) and longitudinal (-15.9 +/- 1.9 vs -20.1 +/- 2.3%, P<0.001) directions and decreased SRIVRT (0.3 +/- 0.15 vs 0.4 +/- 0.2/s, P=0.012) compared to controls. After normalization of corticosteroid excess, LV structural abnormalities reversed, LV circumferential and longitudinal shortening occurred, and SRIVRT normalized. Conclusion: CS induces not only LV hypertrophy and diastolic dysfunction but also subclinical LV systolic dysfunction, which reverses upon normalization of corticosteroid excess.