Nonthyroidal Illness Syndrome and Thyroid Hormone Actions at Integrin α v β 3

Abstract

Context The nonthyroidal illness syndrome (NTIS) is a constellation of changes in circulating thyroid hormone levels that occur in euthyroid patients with acute or chronic systemic diseases. The changes that occur include a reduction in serum T 3, an increase in serum rT 3, and variable changes in circulating T 4 levels. No consensus exists regarding therapeutic intervention for NTIS. Methods We briefly review the published literature on the physiological actions of T 4 and of rT 3 - hormones that until recently have been seen to have little or no bioactivity - and analyze the apparent significance of changes in circulating T 4 and T 3 encountered in the setting of NTIS in patients with cancer. In the case of T 4, these actions may be initiated at a cancer or endothelial cell plasma membrane receptor on integrin αvβ3 or at the cytoskeleton. Results This review examines possible therapeutic intervention in NTIS in patients with cancer in terms of T 4 reduction and T 3 support. Evidence also exists that rT 3 may support cancer. Conclusions Prospective study is proposed of pharmacological reduction of normal or elevated T 4 in cancer-associated NTIS. We also support investigation of normally circulating levels of T 3 in such patients.