- Marc L Miller, MD
Marc L Miller, MD
- Clinical Assistant Professor of Medicine
- Tufts University School of Medicine
- Section Editors
- Ira N Targoff, MD
Ira N Targoff, MD
- Section Editor — Muscle Disease
- Professor of Medicine, Section of Rheumatology
- University of Oklahoma Health Sciences Center
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
Myopathy has been recognized as a side effect of glucocorticoid (corticosteroid) therapy since its introduction as a therapeutic agent in the 1950s . Myopathy can occur with any of the glucocorticoid preparations. The risk may be increased in older patients and in those with cancer or negative nitrogen balance prior to onset of therapy . Similar symptoms can occur in patients with Cushing's syndrome. (See "Epidemiology and clinical manifestations of Cushing's syndrome".)
The major aspects of glucocorticoid-induced myopathy will be reviewed here. Other side effects associated with glucocorticoid therapy, both oral and inhaled, are discussed separately. (See "Major side effects of systemic glucocorticoids" and "Major side effects of inhaled glucocorticoids".)
Glucocorticoids have a direct catabolic effect on skeletal muscle via effects on intermediary metabolism that provide amino acids as a substrate for gluconeogenesis. Activation of the glucocorticoid receptor appears to be involved [3,4], since myopathy can be prevented by a glucocorticoid receptor antagonist .
An additional mechanism in critical illness was suggested in an experimental model. Glucocorticoid therapy interfered with insulin-like growth factor-I (IGF-I) signaling, leading to increased myocyte apoptosis . (See 'Glucocorticoids and neuromuscular blocking agents' below.)
An intracellular signaling molecule with protein kinase activity known as Akt1 (a major isoform of Akt)  may play a central role in the atrophic and hypertrophic responses of muscle to glucocorticoids and IGF-I, respectively [7,8]. Glucocorticoid-induced suppression of Akt1 ultimately results in increased amounts of the ubiquitin-ligase atrogin-1 (MAFbx) that targets muscle proteins for degradation [7,9]. Conversely, IGF-I signaling leads to enhanced activity of Akt1 that suppresses muscle atrophy and that induces muscle hypertrophy .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- BUNIM JJ, ZIFF M, McEWEN C. Evaluation of prolonged cortisone therapy in rheumatiod arthritis: a four-year study. Am J Med 1955; 18:27.
- Afifi AK, Bergman RA, Harvey JC. Steroid myopathy. Clinical, histologic and cytologic observations. Johns Hopkins Med J 1968; 123:158.
- Konagaya M, Bernard PA, Max SR. Blockade of glucocorticoid receptor binding and inhibition of dexamethasone-induced muscle atrophy in the rat by RU38486, a potent glucocorticoid antagonist. Endocrinology 1986; 119:375.
- Sun L, Trausch-Azar JS, Muglia LJ, Schwartz AL. Glucocorticoids differentially regulate degradation of MyoD and Id1 by N-terminal ubiquitination to promote muscle protein catabolism. Proc Natl Acad Sci U S A 2008; 105:3339.
- Singleton JR, Baker BL, Thorburn A. Dexamethasone inhibits insulin-like growth factor signaling and potentiates myoblast apoptosis. Endocrinology 2000; 141:2945.
- Hoffman EP, Nader GA. Balancing muscle hypertrophy and atrophy. Nat Med 2004; 10:584.
- Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004; 117:399.
- Stitt TN, Drujan D, Clarke BA, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 2004; 14:395.
- Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001; 294:1704.
- Dropcho EJ, Soong SJ. Steroid-induced weakness in patients with primary brain tumors. Neurology 1991; 41:1235.
- Ferrando AA, Stuart CA, Sheffield-Moore M, Wolfe RR. Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J Clin Endocrinol Metab 1999; 84:3515.
- Bowyer SL, LaMothe MP, Hollister JR. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunol 1985; 76:234.
- Batchelor TT, Taylor LP, Thaler HT, et al. Steroid myopathy in cancer patients. Neurology 1997; 48:1234.
- Herzog AG. Proximal myopathy associated with inhaled steroids. JAMA 1999; 281:37.
- Boonen S, Van Distel G, Westhovens R, Dequeker J. Steroid myopathy induced by epidural triamcinolone injection. Br J Rheumatol 1995; 34:385.
- Braunstein PW Jr, DeGirolami U. Experimental corticosteroid myopathy. Acta Neuropathol 1981; 55:167.
- Kelly FJ, McGrath JA, Goldspink DF, Cullen MJ. A morphological/biochemical study on the actions of corticosteroids on rat skeletal muscle. Muscle Nerve 1986; 9:1.
- Askari A, Vignos PJ Jr, Moskowitz RW. Steroid myopathy in connective tissue disease. Am J Med 1976; 61:485.
- Khaleeli AA, Edwards RH, Gohil K, et al. Corticosteroid myopathy: a clinical and pathological study. Clin Endocrinol (Oxf) 1983; 18:155.
- Panegyres PK, Squier M, Mills KR, Newsom-Davis J. Acute myopathy associated with large parenteral dose of corticosteroid in myasthenia gravis. J Neurol Neurosurg Psychiatry 1993; 56:702.