Persisting Muscle Dysfunction in Cushing's Syndrome Despite Biochemical Remission

Abstract

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.

Keywords: ACTH; cortisol; diabetes; hypercortisolism; muscle; sarcopenia.

Figure 1.

A: Age- and gender-corrected grip strength (%) in patients with Cushing’s syndrome (CS) at baseline and after successful surgery. Box and whiskers (10^th to 90^th percentile). Baseline: n = 85; 6 months (mo): n = 69; 1 year (y): n = 55; 2 y: n = 34; 3 y: n = 29; 4 y: n = 22; control: n = 29. Comparisons over time were performed by a Wilcoxon signed rank test and comparisons with control by a Mann-Whitney U test. P < 0.05 was considered statistically significant; *P < 0.05 vs baseline, **  P < 0.05 vs 6-mo follow-up, # P < 0.05 vs control; the higher percentage indicates greater muscle strength. B: Relative changes to baseline in mean normalized grip strength (%) of all patients with CS in remission. Data are given as mean ± SEM.

Figure 2.

A: Chair rising test performance (seconds) of patients with Cushing’s syndrome (CS) at baseline and after successful surgery. Box and whiskers (10^th to 90^th percentile). Baseline: n = 78; 6 months (mo): n = 64; 1 year (y): n = 50; 2 y: n = 29; 3 y: n = 28; 4 y: n = 21; control: n = 29. Comparisons over time were performed by a Wilcoxon signed rank test and comparisons with control by a Mann-Whitney U test. P < 0.05 was considered statistically significant; *  P < 0.05 vs baseline, # P < 0.05 vs control. Shorter time (seconds) indicates greater muscle strength. B: Relative changes to baseline in chair rising test performance (%) of all patients with CS in remission. Data are given as mean ± SEM.