Thyroid Hormones, Oxidative Stress, and Inflammation

Abstract

Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

Figure 1

Proposed model of the interrelationships between inflammation, oxidative stress, and thyroid derangement. Inflammation, via hormone and cytokine changes, leads to oxidative stress and also affects thyroid function, causing nonthyroidal illness syndrome or pituitary-thyroid axis depression. At the tissue level, hypothyroidism reinforces the oxidative stress, which in turn worsens hypothyroidism by inhibiting deiodinases, thus establishing a vicious circle (see text for further explanations). AT: angiotensin; FFAs: free fatty acids; IFN: interferon; IL: interleukin; TNF: tumor necrosis factor.

Figure 2

Both hyperthyroidism and hypothyroidism can cause oxidative stress but with different mechanisms. We speculate that nonthyroidal illness syndrome (NTIS) may represent a tissue hypothyroidism condition linked to intracellular and systemic oxidative stress. MDA: malondialdehyde; NO: nitric oxide; PON-1: paraoxonase-1; RNS: reactive nitrogen species; ROS: reactive oxygen species; TAC: total antioxidant capacity.