Thyroid axis function and dysfunction in critical illness

• Published in: Baillière's best practice & research. Clinical endocrinology & metabolism 2011-10, Vol.25 (5), p.745-757
• Main Authors: Mebis, Liese, PhD, Van den Berghe, Greet, MD, PhD
• Format: Article
• Language: English
• Subjects: critical illness; deiodinases; Endocrinology & Metabolism; hypothalamus; non-thyroidal illness; nuclear thyroid receptor (TR); paraventricular nucleus (PVN); retinoid X receptor (RXR); thyroid hormone; thyroid hormone transporter; thyrotropin (TSH); thyrotropin-releasing hormone (TRH)
• ISSN: 1521-690X; 1878-1594
• DOI: 10.1016/j.beem.2011.03.002

Acutely ill patients typically present with low circulating T3 and increased reverse T3. When illness is severe and prolonged, also pulsatile TSH secretion and circulating T4 levels are low. This constellation of changes within the thyroid axis is referred to as the low T3 syndrome or non-thyroidal illness syndrome (NTI), and comprises both peripheral and central alterations in the thyroid axis. Acute alterations are dominated by changes in thyroid hormone binding, in thyroid hormone uptake by the cell and in the activity of the type-1 and type-3 deiodinase enzymes. Prolonged critical illness is associated with a neuroendocrine dysfunction characterized by suppressed hypothalamic thyrotropin-releasing hormone (TRH) expression, resulting in reduced stimulation of the thyrotropes whereby thyroidal hormone release is impaired. During prolonged critical illness, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type 2 deiodinase activity and increased sensitivity at the receptor level. Whether the low T3 syndrome should be treated and which compound should be used remains to be further studied.