AlterationsȱinȱtheȱThyroidȱAxisȱinȱCriticalȱIllness:ȱAȱ

tralia isturbance of the hypothalamo-pituitary-thyroid axis and alteration of circulating thyroid hormones levels are common in non-thyroidal illness (NTI) including infection, burns, and trauma. The commonest abnormality is the low T3 syn-drome due to reduced activity of 5’-deiodinase. In acute illness this is associated with an in-crease in reverse T3 but in more chronic illness reverse T3 is not usually raised. Serum T3 shows a negative correlation with serum concentrations of soluble receptors for TNF and IL-2. Low T3 syndrome may be an appropriate energy-saving adaptation. In critical illness the low T4 syn-drome is common. Both total T4 and T3 levels are low. Serum total T4 inversely correlates with mortality. fT4 measurement in critical illness is problematic because of marked method-depen-dence of results. Direct measurement yields normal/high values but two-step immunoassays used clinically show low values. Falls in the le-vels of serum thyroid hormone binding proteins and alteration to the affinity of hormone binding due to exogenous and endogenous inhibitors of binding generated in illness further complicate in vivo and in vitro assessment. T4 clearance by deiodination is impaired but non-deiodinative pathways are accelerated. Cellular uptake of free hormone is impaired but expression of nuclear thyroid hormone receptors is increased in critical illness. Serum TSH is normal in the low T3 syn-drome but can be low in the low T4 syndrome. Low TSH can be a hypothalamo-pituitary ma-nifestation of illness due to the effect of cyto-kines on TRH release and TSH synthesis, but TSH is also suppressed by dopamine or gluco-corticoid therapy. After drug cessation or in re-covery, TSH can transiently increase above the normal range. TSH in critical illness is less gly-cosylated and less bio-active. Limited trials of T4 and T3 therapy in critical illness have not shown benefit on mortality. No adequate large-scale tri-al has been conducted. KeyWords:Critical illness, Non-thyroidal illness, Thyroid functio