Persisting Muscle Dysfunction in Cushing’s Syndrome Despite Biochemical Remission

Abstract

Context Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing’s syndrome. Its long-term outcome is largely unknown Objective To evaluate long-term muscle function following remission of endogenous Cushing’s syndrome Study design Observational longitudinal cohort study Setting Tertiary care hospitals and specialized outpatient clinic Patients As part of the prospective multicenter German Cushing’s Registry we assessed muscle strength in patients with overt endogenous Cushing’s syndrome. 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 four 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 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 to 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 HbA1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life Conclusion This study shows that Cushing’s syndrome associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting

Cushing Syndrome Associated Myopathy: It Is Time for a Change

“…Cardiac remodeling appears to be only partially explainable by the presence of arterial hypertension in patients with CS. Previous studies showed no correlation Self-reported muscle weakness (in 40%-70 %) [3] Reduced grip strength [31] Prolonged chair rising test time [31] Impaired quality of life associated with low muscle strength [34] Low serum creatine kinase [35] Low plasma myoglobin levels [35] Lower IGF1 levels associated with worse myopathy [63] Decreased muscle fiber conduction velocity [36] Decrease of type 1 and type 2A fibers (11% and 17%) [36] IGF1, insulin-like growth factor 1. In a study using murine C2C12 myotube cultures, the main rodent glucocorticoid corticosterone decreased myotube area, decreased protein synthesis, and increased protein degradation [60].…”

Rationale and design of the cardiovascular status in patients with endogenous cortisol excess study (CV-CORT-EX): a prospective non-interventional follow-up study

“…Proximal myopathy is a relevant clinical finding that is present in about 40-80% of patients with overt CS [13,54,55]. Interestingly, while some reported a higher prevalence of myopathy in males [56], others did not find any sex-related differences [54,55].…”

Salivary profiles of 11-oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia

“…The control group was retrospectively selected from the control group of the German Cushing’s Registry (NeoExNET, ethical approval no. 152-10) after exclusion of Cushing’s syndrome based on a comparable anthropometric profile to the patient cohort (24). Exclusion criteria were defined as any condition or medication known to affect steroid metabolism as well as having worked in shift work during the last three months.…”