Hypothyroid Myopathy
Pathogenesis The pathogenesis of hypothyroid myopathy is not understood. A variety of effects on cellular function and metabolism occurring in hypothyroidism may contribute to the development of muscle symptoms and abnormal muscle function.
Thyroxine (T4) affects energy metabolism. T4 deficiency leads to abnormal glycogenolysis, mitochondrial oxidative metabolism, and triglyceride turnover, which in turn impair muscle function [29-31]. These effects are reflected in selective atrophy of Type II fibers, which are more dependent on glycolysis for their energy supply. Type I hypertrophy may be a compensatory response. With severe or prolonged oxidative damage, muscle cell injury and rhabdomyolysis may occur [17,18]. The fact that the degree of weakness often does not correlate with the biochemical severity of hypothyroidism suggests that muscle injury, rather than impaired muscle function alone, plays a prominent role in some patients [4].
Glucocorticoid induced atrophy
PATHOGENESIS 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 [3].
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 [5]. (See 'Glucocorticoids and neuromuscular blocking agents' below.)
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 induces muscle hypertrophy [8].
In addition to increasing muscle degradation via ubiquitination, glucocorticoids also may reduce muscle differentiation. This effect appears to be mediated by enhanced degradation via ubiquitination of MyoD, which is a master transcriptional switch for muscle development and regeneration [4].
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So the way I see it, hypothyroid would lead to destruction of the muscle = increased release of CPK. In Cushing's the cortisol instead deconstructs the muscle to its constituent parts and uses that material for making glucose or induces apoptosis, thus controlled removal of the cell.
