Nonthyroidal Illness Syndrome and Thyroid Hormone Actions at Integrin αvβ3

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 T3, an increase in serum rT3, and variable changes in circulating T4 levels. No consensus exists regarding therapeutic intervention for NTIS.

Methods: We briefly review the published literature on the physiological actions of T4 and of rT3-hormones that until recently have been seen to have little or no bioactivity-and analyze the apparent significance of changes in circulating T4 and T3 encountered in the setting of NTIS in patients with cancer. In the case of T4, 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 T4 reduction and T3 support. Evidence also exists that rT3 may support cancer.

Conclusions: Prospective study is proposed of pharmacological reduction of normal or elevated T4 in cancer-associated NTIS. We also support investigation of normally circulating levels of T3 in such patients.