title: Modeling the nonthyroidal illness syndrome.
abstract: OBJECTIVE
  To provide an update on the pathogenesis and significance of the nonthyroidal illness syndrome.
  
  
  RESULTS
  The severity of the nonthyroidal illness syndrome predicts mortality, and animal data suggest that, at least in some circumstances, therapy may be beneficial. Multiple abnormalities underlie the syndrome, with induction of type 3 deiodinase and a reduction of type 1 deiodinase potentially contributing to the low T3 state. Induction of type 2 deiodinase in the hypothalamus may underlie the lack of compensatory increase in thyroid-stimulating hormone. Cytokine release from mast cells may be important in establishing a low T4 state secondary to bacterial endotoxin exposure.
  
  
  CONCLUSIONS
  It is important to consider the nonthyroidal illness syndrome when interpreting thyroid function in acute and chronic illness. Substantial insight is being made into the underlying mechanisms, but the role, if any, of therapy is still unknown.
authors.affiliation: Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan 48109-5678, USA. rkoenig@umich.edu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Koenig