Elsevier

Critical Care Clinics

Volume 22, Issue 1, January 2006, Pages 41-55
Critical Care Clinics

Changes Within the Thyroid Axis During Critical Illness

https://doi.org/10.1016/j.ccc.2005.08.006Get rights and content

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Hypothalamus-pituitary-thyroid-axis

Although circulating TSH sharply increases in primary hypothyroidism, it remains within the normal range in critical illness, despite a major decrease in serum T3 and T4 levels [15], [28]. This suggests that there is an altered feedback setting at the hypothalamic-pituitary level [29], [30], [31], [32], which cannot be attributed to exogenous glucocorticoids or dopamine [19]. Animal data show that a reduced expression of TRH, as well as an altered transmembrane transport and enhanced nuclear T3

Thyroid hormone metabolism

Although the changes in serum thyroid hormone levels in the chronic phase of severe illness are mainly of neuroendocrine origin, the peripheral metabolism of thyroid hormone seems to be the main player in the acute phase of severe illness [7], [10], [13], [29], [58]. The combination of decreased serum T3 and increased serum rT3 levels, and thus a decreased T3/rT3 ratio, which occurs within a few hours after the onset of severe stress, suggests major changes in the peripheral metabolism of

Transmembrane transport of thyroid hormone

In addition to serum iodothyronine levels and tissue deiodinase expression, transmembrane transport of iodothyronines is important in the regulation of thyroid hormone bioactivity. Inhibition of transport into hepatocyes leads to a diminished thyroid hormone metabolism, both in vitro and in vivo [78], [79], [80], [81]. Uptake of T4 by human hepatocytes is temperature-, Na-, and energy-dependent [82], and kinetic analyses indicate that T4 and T3 cross the plasma membrane by different

Thyroid hormone substitution

Whether the reduction in serum T3 is an adaptation that results in a decreased metabolic rate and protects against hypercatabolism, or whether it is a mal-adaptation that contributes to a worsening of the disease is still controversial [7], [13], [24]. When determining the possible role for thyroid hormone substitution in critically ill patients, it is important to realize the differences between the acute and the chronic phase of critical illness [13], [14], [29]. The acute changes in the

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    This work was supported by ZonMw Grant 920-03-146 (RPP), and the Fund for Scientific Research–Flanders (YD).

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