What is the role of thyroxine in the pathophysiology of euthyroid sick syndrome?

Updated: Aug 28, 2020
  • Author: Serhat Aytug, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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The decrease in the T4 binding of TBG has been used as an explanation for the low plasma T4 concentration in patients with NTI. The existence of a binding inhibitor could explain the observed alterations in T4 and free T4 fraction. TBG levels usually are within the reference range in patients with NTI and are somewhat lower in critically ill patients with low serum T4. Low TBG levels can be explained, according to some proposals, by rapid protease cleavage at inflammatory sites, particularly in acute inflammatory states (in which the decrease in TBG is too rapid to be accounted for by inhibition of synthesis).

In patients with NTI, serum T4 concentration has been demonstrated to be low because much of the circulating TBG in these patients is desialated. In NTI, the fractional rate of T4 transport from serum to tissues is reduced to 50% of the reference range value. This decrement in fractional rate of T4 transport is not related to the serum levels of total or free T4. Because in illness the reduction in the fractional rate of T4 transport from serum to tissues cannot be attributed to alterations in serum T4 binding, consider other causes such as an impairment of transport into tissues. In nonuremic critical illness, it has been demonstrated that elevated bilirubin or elevated NEFA and low albumin concentration may be at least partially responsible for the T4 transport inhibition in T3-producing tissues (eg, the liver).

A correlation exists between the probability of death and the levels of total T4. When serum T4 levels drop below 4 mcg/dL, the probability of death is about 50%; with serum T4 levels below 2 mcg/dL, the probability of death reaches 80%.

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