Endocrine Abstracts

Dysregulation of types 2 and 3 deiodinases (D2 and D3) alters the metabolism of thyroid hormones in the patients with nonthyroidal illness syndrome (NTIS). Previous studies have demonstrated that deiodinase expression varies in the muscle in different disease models. Nevertheless, the location of D2 and D3 and the effect of oxidative stress on reticulum endoplasmic (ER) and mitochondrial function are not described in human muscle with different types of acute disease and NTIS.ObjectiveEvaluate the location of D2 and D3 mRNA and determine its correlation with ER stress and mitochondrial function in the muscle of NTIS patients.

Methods: A cohort study with 96 critically ill patients was evaluated. Muscle tissue was biopsied on admission to ICU and seven days after. Blood was collected. Ultrasonography (US) of the quadriceps was performed at admission and on day seven. The total carbonyl content and GSH levels were used as a parameter of intracellular redox imbalance. ER stress and mitochondria crosstalk were determined through Grp75, Grp78, PGC1A and COX4. D2 and D3 expressions were localized with in situ hybridization RNAscope.ResultsPatients had a medium age of 59±15 years, majority males, SAPS 64.5±10 and T3 levels of 47±11.2 ng/dL. The formation of carbonyls, a marker of oxidated proteins, was increased (P < 0.001). GSH levels were diminished (P < 0.001). ER and mitochondria studies demonstrated high stress, augmented crosstalk, and apoptosis of these organelles in muscle. Muscle DIO2 (augmented by 5-fold) and DIO3 (augmented by 3-fold) expressions were colocalized on PDGFA, PAX7, and MYOD positive cells and immune muscle cells (positive F4/80 macrophages). Interestingly, US from quadriceps associated lower T3 levels with lower muscle thickness at admission. Moreover, on day seven, muscle US showed extensive fiber derangement when compared to day one.ConclusionMuscle alterations on ER and mitochondria were directly correlated with deiodinase expression and location, T3 levels and mortality, independently of the initial disease.