Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock

• Published in: Clinical endocrinology (Oxford) 2008-05, Vol.68 (5), p.821-827
• Main Authors: Rodriguez-Perez, Alfonso, Palos-Paz, Fernando, Kaptein, Ellen, Visser, Theo J., Dominguez-Gerpe, L., Alvarez-Escudero, Julian, Lado-Abeal, Joaquin
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Case-Control Studies; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic; Humans; Iodide Peroxidase - metabolism; Male; Medical sciences; Middle Aged; Muscle, Skeletal - metabolism; Shock, Septic - complications; Shock, Septic - metabolism; Thyroid Diseases - etiology; Thyroid Diseases - metabolism; Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2007.03102.x

Summary Objective  Septic shock is one of various causes of nonthyroidal illness syndrome (NTIS). In humans, the molecular mechanisms involved in NTIS are mostly unknown. The aim of this study was to investigate, in patients with NTIS secondary to septic shock, changes in the expression of genes involved in the actions of thyroid hormones and in the activity of deiodinase enzymes, in two tissues important for protein and energy metabolism, skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Design  Hospitalized patients were divided into a control and a septic shock NTIS group. Measurement  Serum collection for biochemical measurements, and SM and SAT biopsies for mRNA expression analysis of thyroid hormone receptors (THRB1, THRA1), retinoid X receptors (RXRA, RXRB, RXRG), nuclear receptor corepressor (NCOR1), silencing mediator of retinoid and thyroid hormone receptor (SMRT), steroid receptor coactivator (SRC1), type 1 and 2 deiodinases (D1, D2), monocarboxylate transporter 8 (MCT8), SECIS binding protein 2 (SBP2) and uncoupling protein 3 (UCP3) as well as D1, D2 and D3 enzyme activity measurements. Results  The NTIS group had lower serum TSH, and free T3 and higher rT3 than controls. D1 and D3 were detected in SAT, with no differences found between the two groups; SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls. SM expression of THRB1, RXRG and D2 was lower and RXRA higher in NTIS than controls. SAT from NTIS patients had lower MCT8, THRB1, THRA1, RXRG and SMRT, and higher UCP3 expression than controls. Conclusions  In patients with septic shock NTIS tissue responses are orientated to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3, as well as to decrease thyroid hormone actions.