Tissue thyroid hormone levels in critical illness

Context: Pronounced alterations in serum thyroid hormone levels occur during critical illness. T(3) decreases and rT(3) increases, the magnitudes of which are related to the severity of disease. It is unclear whether these changes are associated with decreased tissue T(3) concentrations and, thus, reduced thyroid hormone bioactivity. Patients and Study Questions: We therefore investigated, in 79 patients who died after intensive care and who did or did not receive thyroid hormone treatment, whether total serum thyroid hormone levels correspond to tissue levels in liver and muscle. Furthermore, we investigated the relationship between tissue thyroid hormone levels, deiodinase activities, and monocarboxylate transporter 8 expression. Results: Tissue iodothyronine levels were positively correlated with serum levels, indicating that the decrease in serum T(3) during illness is associated with decreased levels of tissue T(3). Higher serum T(3) levels in patients who received thyroid hormone treatment were accompanied by higher levels of liver and muscle T(3), with evidence for tissuespecific regulation. Tissue rT(3) and the T(3)/rT(3) ratio were correlated with tissue deiodinase activities. Monocarboxylate transporter 8 expression was not related to the ratio of the serum over tissue concentration of the different iodothyronines. Conclusion: Our results suggest that, in addition to changes in the hypothalamus-pituitary-thyroid axis, tissue-specific mechanisms are involved in the reduced supply of bioactive thyroid hormone in critical illness.