Endocrine Abstracts (2009) 20 S14.3

Molecular basis of non thyroidal illness syndrome

Joaquin Lado-Abeal1,2

1University Health Sciences Center, Lubbock, Texas, USA; 2UETeM. Medical School. University of Santiago de Compostela, Santiago de Compostela, Spain.

The term nonthyroidal illness syndrome (NTIS) refers to characteristic changes in thyroid hormone (TH) levels during illness and starvation. These changes are low T3 and high rT3 in serum and tissues, normal or low serum T4 and inappropriately normal or low serum TSH. It remains unclear whether NTIS is a beneficial adaptive response to reduce energy consumption, or a form of secondary hypothyroidism that requires TH treatment, and there is no clinical evidence that TH treatment is advantageous, or indeed disadvantageous.

NTIS patients have an impairment of hypothalamic–pituitary function. The increase in proinflammatory cytokines and endogenous glucocorticoids typically seen in critically ill patients, together with administration of glucocorticoids and dopaminergic drugs, could directly suppress TRH secretion, the pituitary response to TRH and TSH secretion.

About 80% of T3 is produced by extrathyroidal deiodination of T4. In NTIS low T3 and high rT3 are related to a decrease in liver type 1 iodothyronine deiodinase (D1) and skeletal muscle (SM)-D2 activities and to the increase of D3 activity in liver and SM.

NTIS patients show decreased T4 and T3 in most tissues caused in part by reduced uptake, although this is not limiting if appropriate replacement therapy is given.

TH action depends on the tissue expression of TH receptors (TRs), retinoid X receptor (RXR) and corepressors and coactivators. In patients with NTIS THRB1 and RXRG expression decreased in SM and adipose tissue and THRA1 expression and MCT8 transporter decreased in adipose tissue, indicating a decreased potential for TH. Septic NTIS patients showed a decrease in D2 expression and an increase in D3 activity in SM, but no changes in deiodinase activities were observed in adipose tissue. Septic shock NTIS patients tend to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3 that probably decrease TH actions.

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