Patients with low IGF-I after curative surgery for Cushing's syndrome have an adverse long-term outcome of hypercortisolism-induced myopathy.

BACKGROUND Glucocorticoid excess leads to muscle atrophy and weakness in patients with endogenous Cushing's syndrome. Insulin-like growth factor I (IGF-I) is known to have protective effects on muscle loss. We hypothesized that individual serum IGF-I concentrations might be predictive for long-term myopathy outcome in Cushing's syndrome. PATIENTS AND METHODS In a prospective longitudinal study of 31 patients with florid Cushing's syndrome, we analyzed IGF-I and IGF binding protein 3 (IGFBP 3) concentrations at the time of diagnosis and following surgical remission over a period of up to three years. We assessed muscle strength by grip strength measurements using a hand grip dynamometer and muscle mass by bio-impedance measurements. FINDINGS Individual serum IGF-I concentrations in the postoperative phase were strongly predictive of long-term grip strength outcome (rs = 0.696, p ≤ 0.001). Also, lower IGF-I concentrations were associated with a lower muscle mass after three years (rs = 0.404, p = 0.033). While patients with high IGF-I SD scores (> 1.4) showed an improvement in grip strength within the follow-up period (p = 0.009), patients with lower IGF-I SD scores (≤ -0.4) had a worse outcome with persisting muscle dysfunction. In contrast, preoperative IGF-I concentrations during the florid phase of Cushing's syndrome did not predict long-term muscle function outcome (rs = 0.285, p = 0.127). CONCLUSION Lower individual IGF-I concentrations six months after curative surgery for Cushing's syndrome are associated with adverse long-term myopathy outcome and IGF-I might be essential for muscle regeneration in the early phase after correction of hypercortisolism.