Persisting Muscle Dysfunction in Cushing's Syndrome Despite Biochemical Remission

Context: Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing's syndrome (CS). Its long-term outcome is largely unknown. Objective: To evaluate long-term muscle function following the remission of endogenous CS. Study Design: Observational longitudinal cohort study. Setting: Tertiary care hospitals and a specialized outpatient clinic. Patients: As part of the prospective multicenter German Cushing's Registry, we assessed muscle strength in patients with overt endogenous CS. We studied the patients at the time of diagnosis (n = 88), after 6 months (n = 69), and thereafter annually, following surgical remission over a period of up to 4 years (1 year: n = 55; 2 years: n = 34; 3 years: n = 29; 4 years: n = 22). Muscle function was evaluated by hand grip strength and by chair rising test. Results: Grip strength was decreased to 83% of normal controls (100%) at the time of diagnosis. It further decreased to 71% after 6 months in remission (P <= 0.001) and showed no improvement during further follow-up compared with baseline. Chair rising test performance improved initially (8 seconds at baseline vs 7 seconds after 6 months, P= 0.004) but remained at this reduced level thereafter (7 seconds after 3 years vs 5 seconds in controls, P= 0.038). In multivariate analysis, we identified, as predictors for long-term muscle dysfunction, age, waist-to-hip ratio, and hemoglobin A1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life. Conclusion: This study shows that CS-associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting.