Graves DZ
Actions of Thyroid Hormone and Mechanism of Graves’ Disease Thyroid hormones are capable of acting at nearly every organ system in the human body. They promote bone formation, increase basal metabolic rate, heat production, oxygen consumption, and they alter the cardiovascular and respiratory systems resulting in an increased blood flow and oxygen delivery to the tissues. A quick summary of thyroid hormone synthesis, taken directly from the Kopp article, is included at the end of this learning issue. The first step in the action of thyroid hormone is the conversion of T4 to the active T3 by a 5’-iodinase. Once T3 has entered the target cell it enters and binds to a nuclear receptor, this complex binds to a specific regulatory element in the DNA where it stimulates DNA transcription and ultimately protein synthesis. Interestingly, certain states such as pregnancy, fasting, stress, and β-blockers can decrease the levels of T3 and increase the levels of rT3, which is physiologically inactive. The effects of thyroid hormone are generally organ specific, although several effect are more generalized. One of the most significant and noticeable effects of thyroid hormone is an increase in oxygen consumption, which leads to an increase in both basal metabolic rate and body temperature. The increase in oxygen consumption is seen in every tissue except the brain, gonads, and spleen, and it is caused by an increase in the synthesis and activity of the Na+-K+ ATPase. The metabolism is increased to meet the increased oxygen consumption through a potentiation of gluconeogenesis, lipolysis, and proteolysis in order to provide the metabolic substrates necessary for oxidative metabolism. The effects on cardiac tissue, which are covered extensively elsewhere, include an increase in cardiac output due to increase in heart rate and myocardial contractility, which are directly related to an increased synthesis of myosin, β1-adrenergic receptors, and Ca2+ ATPase.