Thyroid hormones affect growth, development and metabolism of vertebrates, and are considered the main regulators of their homeostasis. On the other hand, elevated circulating levels of thyroid hormones are associated with modifications in the whole organism (weight loss and increased metabolism and temperature) and in several body regions. Indeed, tachycardia, atrial arrhythmias, heart failure, muscle weakness and wasting, bone mass loss, and hepatobiliary complications are commonly found in hyperthyroid animals and humans.
Most of the thyroid hormone actions result from influences on transcription of T3-responsive genes, which are mediated through nuclear receptors. However, there is significant evidence for involvement of tissue oxidative stress in some dysfunctions shown in hyperthyroid state.
Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction, through several mechanisms including increased expression of uncoupling proteins, proteolytic enzymes and transcriptional coactivator PGC-1, and stimulated opening of permeability transition pores. Actually, examination of the most recent data confirms that, in hyperthyroid state, mitochondria play a major role in tissue oxidative stress and rescue from excessive dysfunction. However, such data have also shown the substantial interplay between mitochondria and other sources of ROS and the role that, in pathological conditions, such sources play in generating oxidative stress and promoting survival mechanisms, such as autophagy and apoptosis. These observations suggest that cellular ROS producers could provide a significant contribution to processes that, in hyperthyroid state, oxidatively damage tissues and assure their survival.