Persisting Muscle Dysfunction in Cushing's Syndrome Despite Biochemical Remission

Frederick Vogel; Leah T. Braun; German Rubinstein; Stephanie Zopp; Heike Künzel; Finn Strasding; Adriana Albani; Anna Riester; Ralf Schmidmaier; Martin Bidlingmaier; Marcus Quinkler; Timo Deutschbein; Felix Beuschlein; Martin Reincke


J Clin Endocrinol Metab. 2020;105(12) 

In This Article

Abstract and Introduction


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.


Glucocorticoid-induced myopathy with self-reported muscle weakness is present in up to 60% of patients with florid Cushing's syndrome (CS). It is reported to be more frequent in men than in women.[1,2] The development of proximal muscle wasting and weakness is also a typical side effect of systemic glucocorticoid treatment. Based on the common use of steroids for the treatment of several medical conditions, exogenous glucocorticoids have become the most common reason for drug-induced myopathy.[3]

Cushing's syndrome-associated myopathy particularly affects the proximal part of the limbs.[4] The clinical management of glucocorticoid-induced myopathy is difficult, as patients typically experience relevant muscular impairment at the time of initial diagnosis. Quantitative muscle ultrasound is proposed to be a useful diagnostic tool for the detection of CS before the development of symptoms.[5] A specific therapy is not available so far, and current treatment recommendations consist of adequate protein intake and moderate physical exercise.[6–9] Given that endogenous CS is a rare disease, so far, associated myopathy has been studied only in small patient cohorts. Several characteristic clinical features of CS, including cognitive impairments, fatigue, and an increased cardiovascular risk, can persist even years after a successful cure.[10,11] We and others have suggested that CS-associated myopathy and muscle damage may continue in the early recovery phase after successful treatment,[12–14] but its long-term prognosis and outcome is unknown. In retrospective, cross-sectional studies, patients in long-term remission showed decreased muscle strength and a lower aerobic exercise capacity compared to controls.[14,15] Whether this finding is due to a long-term change of muscle fibers in terms of an irreversible myopathy or due to a persisting cardiorespiratory dysfunction remains controversial. To analyze the long-term outcome of muscle dysfunction in CS, we evaluated the prospective data of the German Cushing's Registry.