The widespread use of adrenal corticosteroids has created a class of muscle diseases similar to the one that occurs in the Cushing disease as described many decades ago by Müller and Kugelberg. A deficiency of corticosteroids, as occurs in Addison disease, also causes generalized weakness and asthenia, but without an identifiable muscle disease.
The prolonged use of corticosteroids causes the proximal limb and girdle musculature to become weak to the point of causing difficulty in elevating the arms and arising from a sitting, squatting, or kneeling position; walking upstairs may also be hampered. Some individuals seem to be more susceptible than others. The problem often arises of distinguishing an iatrogenic steroid-induced myopathy from the weakness produced by a primary neuromuscular disorder that is being treated with these medications such as one of the myositides or myasthenia. In some of our myasthenic patients, the use of high-dose corticosteroids has resulted in a selective, rapid, and severe weakness of the hip flexors.
The EMG is normal or mildly myopathic, with small and abundant action potentials but no fibrillations. Biopsies disclose only a slight variation in fiber size with atrophic fibers, mainly of type 2b, but little or no fiber necrosis and no inflammatory cells. Under electron microscopic examination there are aggregates of mitochondria, accumulations of glycogen and lipid, and slight myofibrillar loss that suggest more disuse atrophy than they do a primary muscle disorder. The serum CK and aldolase are usually normal. These changes are the same in Cushing disease and an otherwise unexplained proximal myopathy with these features suggests that diagnosis (Cushing disease and Cushing syndrome).
There is an imprecise correlation between the total dose of corticosteroid administered and the severity of muscle weakness. Nevertheless, in patients who develop this type of myopathy, the corticosteroid dosage has usually been high and sustained over a period of months or years. All corticosteroids may produce the disorder, although fluorinated ones, on uncertain evidence, are said to be more culpable than others. Discontinuation or reduction of corticosteroid administration leads to gradual improvement and recovery; alternate-day regimens may also allow recovery, albeit gradually.
As the foregoing discussion implies, the mechanism by which corticosteroids cause muscle weakness is not known. In corticosteroid-treated animals, there is a measurable decrease in the uptake of amino acids and protein synthesis by muscle, but the underlying pathways have not been elucidated. This has even greater bearing on the next discussed subject.
In addition to the proximal myopathy induced by the long-term use of steroids, an acute and far more severe myopathy has been recognized in critically ill patients. It was described initially with cases of severe asthma in patients who were exposed to high doses of steroids for treatment. Subsequently, this acute myopathy has been recognized with all types of critical systemic diseases and organ failure, again, usually in the context of the administration of high doses of corticosteroids but in a few cases, with sepsis and shock without exposure to this class of medication. Moreover, the use of neuromuscular blocking agents appears to play an important complementary role in the genesis of the myopathy, being reported as a factor in more than 80 percent of cases; it is uncertain whether these agents alone, without sepsis or organ failure, can produce a similar process (see reviews by Gorson and
Ropper, Lacomis et al, and Barohn et al).