B6.054 Steroid Myopathies Flashcards
symptoms of myopathy
difficulty climbing stairs. standing falls trouble combing hair, brushing teeth dysphagia / dysarthria fatigue, myalgia, tenderness
signs of myopathy
proximal weakness: neck, shoulder, hip
normal tendon reflexes
normal sensory exam
facial or bulbar weakness
Ddx for myopathy
myositis MD toxic exposure: SANAM metabolic enzyme defect mitochondrial muscle disease endocrinopathy critical illness myopathy
Ddx for proximal muscle weakness
myopathy NMJ defect (lambert eaton, MG) CIDP (inflammation of peripheral nerves) motor neuron diseases: SMA, ALS myelopathy sarcopenia
when does muscle aging start?
age 40
lab evaluation of myopathic disorders
serum CK electrolytes, thyroid serum Abs needle EMG nerve conduction study biopsy non-ischemic forearm test urine for myoglobin muscle imaging molecular/genetic studies
how might you get an excess of endogenous steroids
Cushings > bilateral adrenalectomy > excessive pituitary ACTH secretion > proximal myopathy (Nelson Syndrome)
which steroids are particularly likely to cause drug induced steroid myopathy
9-a-fluorinated corticosteroids
triamcinolone, betamethasone, dexamethasone
(long duration)
which steroids rarely cause myopathy
prednisone dose equivalent < 30 mg qd
complications of critical illness
CIM: critical illness myopathy
CIN: critical illness neuropathy
PNMB: prolonged neuromuscular blockade
mechanisms of steroid myopathy
not fully understood
likely due to impaired protein synthesis and muscle catabolism
which muscle fibers are more susceptible to steroid myopathy
type 2 fibers (fast, glycolytic)
cellular transcription changes caused by steroids that can induce myopathy
induced ubiquitin ligases: atrogin 1, muscle RING finger 1
suppress mammalian/ mechanistic target of rapamycin (mTOR)
these changes lead to an imbalance between anabolism and catabolism of muscle proteins, resulting in atrophy
growth factor changes contributing to steroid myopathy
negative changes in IGF-1 and myostatin
muscle weakness pattern associated with Cushings
insidious onset
proximal muscle weakness and wasting without involvement of distal or cranial muscles
fat redistribution in Cushings
supraclavicular and temporal fossa
facial rounding
central obesity
buffalo hump