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The Thermogenic Effect of Thyroid Hormone and Its Clinical Implications

J. Enrique Silva, MD
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From Jewish General Hospital, Montreal, Quebec, Canada.

Ann Intern Med. 2003;139(3):205-213. doi:10.7326/0003-4819-139-3-200308050-00018
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Evolutionary development of homeothermy was an important biological advance because it allowed animal life to expand into environments with temperatures markedly different from those of the body. Tight control of body temperature homeostasis required the selection of several different mechanisms in the course of evolution that are activated whenever the body's basal heat production is insufficient or excessive. This maintains the core temperature at its setting. Reflecting the fact that the habitat is usually colder than the body, a mainstay of homeothermy is the inherent capacity of homeothermic species to constantly generate more heat than poikilothermic animals.


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Figure 1.
The various forms of thermogenesis in homeothermic species.

The horizontal line on the right vertical axis indicates that body temperature stays constant, independent of the environment. Thermoneutrality temperature, indicated on the x-axis, is the ambient temperature at which obligatory thermogenesis is sufficient to maintain body temperature without the participation of thermoregulatory mechanisms. In humans, this temperature is approximately 23 °C. See text for details.

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Figure 2.
Energy transformations in biological systems.ATP3

The energy released from substrate oxidation is captured in adenosine triphosphate ( ) and then transferred from this molecule to others to provide energy for the biological processes. A fraction of the energy involved both in the synthesis of ATP and in its utilization is lost as heat. While this fraction is low and constant in ATP utilization, the fraction dissipated as heat in ATP synthesis is higher and apparently subject to regulation. Thyroid hormone increases heat production by increasing ATP utilization and by reducing the thermodynamic efficiency of ATP synthesis. See text for details. ADP = adenosine diphosphate; P = inorganic phosphate; T = triiodothyronine.

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Figure 3.
Mechanism of action of uncoupling proteins (UCPs) and uncouplers in general.H+ATPADP

The energy released in the oxidation of substrates in the mitochondria is transiently accumulated in the form of a proton ( ) gradient created as the electrons from the oxidized substrate are transferred downstream along the respiratory chain. The energy accumulated in this gradient is used by the adenosine triphosphate ( ) synthase to produce ATP from adenosine diphosphate ( ), which is an endothermic reaction. Uncouplers reduce this gradient, bypassing the ATP synthase. The movement of protons down the gradient is an exothermic process. Uncoupling proteins, the best known and best characterized of which is the brown adipose tissue UCP (now called UCP1), allow the protons to reenter the mitochondria in a regulated manner. P = inorganic phosphate.

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Figure 4.
Correlation between resting energy expenditure (REE), which largely reflects obligatory thermogenesis, and thyroid-stimulating hormone (TSH) in hypothyroid patients receiving maintenance L-thyroxine replacement therapy.FFMLrPrP

Resting energy expenditure has been corrected by lean body mass or fat-free mass ( ). After the initial evaluation, the dose of -thyroxine was slightly changed to move the TSH level around the normal range. In the top panel, = 0.92 and < 0.001; in the bottom panel, = 0.82 and < 0.007. See reference 35 and the text for details. Adapted with permission from al-Adsani H, Hoffer LJ, Silva JE. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab. 1997;82(4):1118-25; copyright owner, The Endocrine Society.

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Figure 5.
The changes in thermogenesis that occur in thyrotoxicosis and hypothyroidism.

For comparison with the euthyroid state, see Figure 1 (figures are on scale). The heat derived from the minimal energetic cost of living changes little with thyroid status. The most important component of thermogenesis affected by thyroid status is basal thermogenesis. Facultative thermogenesis is reduced in both states but for different reasons. Thermoneutrality temperature is displaced down in thyrotoxicosis and up in hypothyroidism. See text for further details.

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