Thyroid hormone metabolism in nonthyroidal illness : Current Opinion in Endocrinology, Diabetes and Obesity

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Thyroid hormone metabolism in nonthyroidal illness

Wiersinga, Wilmar M. MD, PhD; Boelen, Anita PhD

Current Opinion in Endocrinology and Diabetes 3(5):p 422-427, October 1996.


During illness profound changes may occur in thyroid hormone metabolism, collectively known as nonthyroidal illness (NTI) or the sick euthyroid syndrome. These changes include a decrease of serum triiodothyronine (T3) and an increase of serum reverse triiodothyronine (rT3); in severe cases plasma thyroxine (T4) and thyroid-stimulating hormone also decrease. They depend on the severity of the disease (the greater the changes, the higher the mortality), the nutritional state, and the type of disease (eg, NTI in HIV-infected patients differs from non-HIV NTI by the absence of a rise of serum (rT3). NTI may develop very rapidly-within hours after cardiopulmonary bypass surgery. Treatment of NTI with exogenous T3 has not shown so far to be of clinical benefit to the patient. Progress is being made in unraveling the pathogenesis of NTI. In renal insufficiency the accumulation of a furan fatty acid and indoxyl sulfate in serum inhibit T4 transport into the liver, thereby reducing the 5'-deiodination. Likewise, inhibition of T4 transport by elevated serum bilirubin and free fatty acids may contribute to the low serum T3 levels in critically ill patients. Serum T3 is negatively correlated to a variety of serum cytokine proteins; the variability of serum T3 is explained for 35% by changes in serum sTNFaRp75 and for 14% by changes in serum IL-6. The administration of TNFa, IL-6, or IFNa to human volunteers induces changes resembling those of NTI. Illness activates the cytokine network resulting in the acute phase response, and NTI may be viewed as part of this defense mechanism of the body to save energy during illness. Further studies on the effect of blocking the action of cytokines during the induction of illness are awaited for definitive evidence of a pathogenetic role of cytokines in NTI.

© Lippincott-Raven Publishers.

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