Steroid induced myopathy

The functional and histologic picture of steroid-induced myopathy was systematically examined in eight patients with chronic obstructive pulmonary disease (COPD) and compared with control patients with COPD matched for age, sex, and degree of airflow obstruction. Steroid-induced myopathy was associated with severe peripheral muscle weakness, quadriceps force being 23 +/- 14 versus 71 +/- 23% in control patients with COPD (p < ). In addition, clear ventilatory muscle weakness was present. PImax was 37 +/- 15 versus 67 +/- 24% in control patients (p < ), and PEmax averaged 34 +/- 10 versus 74 +/- 23% (p < ). Vital capacity tended to be slightly reduced compared with that in control patients (69 +/- 21 versus 80 +/- 16%, p = ). The only biochemical abnormalities associated to steroid-induced myopathy were a moderately increased lactic dehydrogenase level (697 +/- 301 versus 421 +/- 128 IU/L, p < ) and an increased creatine excretion in 24-h urine (990 +/- 609 versus 159 +/- 219 mg/24 h, p< ). On quadriceps biopsy steroid-induced myopathy was characterized by increased variation in diameter of fibers, with several angular atrophic fibers and diffuse necrotic and basophilic fibers. In addition, increased amount of connective tissue in between fibers and increased number of subsarcolemmal and central nuclei were present. On ATPase stain diffuse fiber atrophy predominantly affecting fast fibers was present, but there was no indication that atrophy was confined to type IIb fibers in contrast to conventional thinking. On follow-up, survival of patients with steroid-induced myopathy was reduced in comparison with control patients with COPD with similar degree of airflow obstruction (p < ).

An intracellular signaling molecule with protein kinase activity known as Akt1 (a major isoform of Akt) [ 6 ] 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 [ 8 ].

During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every six hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenal cortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenal cortical suppression for 1¼ to 1½ days following a single dose) and thus are recommended for alternate day therapy.

Steroid induced myopathy

steroid induced myopathy


steroid induced myopathysteroid induced myopathysteroid induced myopathysteroid induced myopathysteroid induced myopathy