Induced Types 2 and 3 Deiodinase in Non-Thyroidal Illness Syndrome and the Implications to Critical Illness-Induced Myopathy—A Prospective Cohort Study

Loss of muscle mass and strength is a common condition associated with adverse outcomes in critically ill patients. Here, we determined the correlation between non-thyroidal illness (NTIS) and molecular alterations in the muscle of critically ill individuals. We evaluated deiodinase expression, intramuscular triiodothyronine (T3) levels, and mitochondria and sarcoplasmic reticulum components. The cellular colocalization of the enzymes and its influence on myocytes and genes regulated by T3 were shown, including those of mitochondria. A prospective cohort of 96 patients. Blood and muscular samples were collected on admission to the intensive care unit (ICU), as well as clinical data and ultrasonographic measurements. Patients with NTIS showed increased oxidative stress markers associated with critical illness in muscle biopsy, such as carbonyl content and low sulfhydryl and GSH. The distribution pattern of deiodinases in muscle and its biochemical properties showed significant pathophysiological linkage between NTIS and muscle loss, as type 3-deiodinase (D3) was highly expressed in stem cells, preventing their differentiation in mature myocytes. Despite the high type 2-deiodinase (D2) expression in muscle tissue in the acute phase of critical illness, T3 was unmeasurable in the samples. In this scenario, we also demonstrated impaired expression of glucose transporters GLUT4, IRS1, and 2, which are involved in muscle illness. Here, we provide evidence that altered thyroid hormone metabolism contributes to stem cell dysfunction and further explain the mechanisms underlying critical illness-induced myopathy.