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

in European Journal of Endocrinology
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  • 1 Medizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-Universität München, Munich, Bayern, Germany
  • 2 Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, UniversitätsSpital Zürich, Zurich, Switzerland

Correspondence should be addressed to M Reincke; Email: Martin.Reincke@med.uni-muenchen.de

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 3 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 3 years (rs = 0.404, P  = 0.033). While patients with high IGF-I s.d. scores (SDS; >1.4) showed an improvement in grip strength within the follow-up period (P  = 0.009), patients with lower IGF-I SDS (≤−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 6 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.

Supplementary Materials

    • Supplement Table 1. Correlation analysis between the IGF-I SD score at different time points and age and gender corrected grip strength (normalized grip strength) in patients with CS. Preoperative (Florid CS) and follow-up assessments before and after curative treatment of CS.
    • Supplement Figure 1. Age and gender corrected grip strength (normalized grip strength, % of normal controls) in patients with Cushing&#x2019;s syndrome (CS) preoperative during hypercortisolism (gray shaded) and after curative surgery (mo = months; y = years). Florid CS n=31, 6 mo n=29, 1 y n=29, 2 y n=27, 3 y n=31. Higher percentage indicates greater muscle strength. Box and whiskers (10-90 percentile). Comparisons were performed by a Wilcoxon signed rank test; p<0.05 was considered statistically significant. * p<0.05 versus Florid CS, ** p<0.05 versus 6 months follow-up.
    • Supplement Figure 2. Relationship between IGF-I standard deviation (SD) score change from florid Cushing&#x2019;s syndrome (CS) preoperative to 6 months after curative surgery, and age and gender corrected grip strength (normalized grip strength, % of normal controls) after 3 years in remission. Line indicates estimated linear regression line. N = 29, Spearman&#x2018;s coefficient 0.493, R2 = 0.258, p = 0.007.
    • Supplement Figure 3. IGF-I standard deviation (SD) scores in patients with Cushing&#x2019;s syndrome (CS) preoperative during hypercortisolism (Florid CS) and the further course 6 and 12 months (mo) after curative surgery, respectively. Each line represents a single patient. Florid CS n=31, 6 mo n=29, 12 mo n=29.

 

     European Society of Endocrinology

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