The thyroid gland, found in Chapter 42 of this medical textbook, plays a significant role in various metabolic processes. Thyroid hormone accelerates the physiological response to starvation by promoting lipolysis, ketogenesis, and proteolysis. It also stimulates the synthesis of bile acids from cholesterol and enhances biliary secretion, resulting in decreased levels of total and low-density lipoprotein cholesterol in the body pool and plasma. Additionally, thyroid hormone increases the metabolic clearance of adrenal and gonadal steroid hormones, certain B vitamins, and administered drugs.

Thyroid hormones have an impact on thermogenesis by affecting the utilization and synthesis of adenosine triphosphate (ATP). They enhance ATP utilization by upregulating energy-dependent processes like Na+,K+-ATPase and SERCA. In skeletal muscle, thyroid hormone promotes calcium cycling between the cytoplasm and sarcoplasmic reticulum, generating heat. It has been discovered that brown fat, previously thought to be important only in neonates, also plays a role in facultative thermogenesis in adults. Brown fat contains uncoupling protein-1 (UCP1) or thermogenin, which dissipates the proton gradient across the inner mitochondrial membrane as heat. Thyroid hormone regulates UCP1, and brown fat expresses D2, which converts T4 to T3 intracellularly. The interaction between thyroid hormones and the sympathetic nervous system is crucial for brown fat thermogenesis, with catecholamines promoting lipolysis and increasing expression of D2. T3, in turn, upregulates adrenergic receptors and enhances catecholamine responsiveness. Heat intolerance is observed in hyperthyroidism, while cold intolerance is seen in hypothyroidism.

Thyroid hormone not only enhances oxygen (O2) utilization but also facilitates O2 delivery. T3 increases the resting respiratory rate, minute ventilation, and the ventilatory response to hypercapnia and hypoxia, ensuring normal arterial PO2 levels during increased O2 utilization and normal PCO2 levels during increased CO2 production. Furthermore, thyroid hormone stimulates the production of erythropoietin by the kidney, resulting in a slight increase in hematocrit to enhance O2-carrying capacity.

Optimal amounts of thyroid hormone are essential for the normal functioning of skeletal muscles. It is believed that this requirement is linked to the regulation of energy production and storage. Thyroid hormone excess leads to increased glycolysis and glycogenolysis, along with reduced levels of glycogen and creatine phosphate. Consequently, the inability of muscles to take up and phosphorylate creatine results in its increased urinary excretion.

The autonomic nervous system and catecholamine action also exhibit a synergistic relationship with thyroid hormones. Thyroid hormones work in conjunction with catecholamines to increase the metabolic rate, heat production, heart rate, motor activity, and excitation of the central nervous system (CNS). T3 has the ability to enhance sympathetic nervous system activity by increasing the number of β-adrenergic receptors in heart muscle and promoting the generation of cyclic adenosine monophosphate (cAMP) as an intracellular second messenger.
CHAPTER 42 The Thyroid Gland lipolysis, ketogenesis, and proteolysis of the labile protein pool. The overall metabolic effect of thyroid hormone has been aptly described as accelerating the physiological response to starvation. In addition, thyroid hormone stimulates synthesis of bile acids from cholesterol and promotes biliary secretion. The net effect is a decrease in the body pool and plasma levels of total and low-density lipoprotein cholesterol. Metabolic clearance of adrenal and gonadal steroid hormones, some B vitamins, and certain administered drugs is also increased by thyroid hormone.
Thyroid hormones stimulate thermogenesis by affecting both adenosine triphosphate (ATP) utilization and the efficiency of ATP synthesis. ATP utilization is enhanced by upregulation of several energy-dependent processes, including Na+,K+-ATPase and SERCA, particularly in skeletal muscle, where calcium cycling between the cytoplasm and sarcoplasmic reticulum uses ATP and generates heat. Recently it has been demonstrated that brown fat in humans, once thought to be important only in neonates, appears to play a role in facultative thermogenesis in adults. Imaging studies have demonstrated the presence of brown fat in the mediastinum, particularly in lean individuals, and metabolic activity in brown fat is enhanced by exposure to cold. Brown fat expresses uncoupling protein-1 (UCP1), also called thermogenin, which causes the proton gradient across the inner mitochondrial membrane to be dissipated as heat, which is then disseminated to the rest of the body by the circulation. UCP1 is regulated by thyroid hormone, and brown fat expresses D2, providing intracellular conversion of T4 to T3. Brown fat thermogenesis involves a synergistic interaction between thyroid hormones and the sympathetic nervous system. Catecholamines promote lipolysis and upregulate expression of D2. T3 in turn upregulates adrenergic receptors and enhances catecholamine responsiveness. Hyperthyroidism is accompanied by heat intolerance, whereas hypothyroidism is accompanied by cold intolerance.
Thyroid hormone stimulates O2 utilization and enhances O2 delivery. Appropriately, T3 increases the resting respiratory rate, minute ventilation, and the ventilatory response to hypercapnia and hypoxia. These actions maintain a normal arterial PO2 when O2 utilization is increased and a normal PCO2 when CO2 production is increased. Additionally the hematocrit increases slightly to enhance O2-carrying capacity. This increase results from stimulation of erythropoietin production by the kidney.
Normal function of skeletal muscles also requires optimal amounts of thyroid hormone. This requirement may be related to regulation of energy production and storage. Glycolysis and glycogenolysis are increased, whereas glycogen and creatine phosphate are reduced by thyroid hormone excess. The inability of muscle to take up and phosphorylate creatine leads to its increased urinary excretion.
Effects on the Autonomic Nervous System and Catecholamine Action
As already mentioned, there is important synergism between catecholamines and thyroid hormones. Thyroid hormones are synergistic with catecholamines in increasing the metabolic rate, heat production, heart rate, motor activity, and excitation of the CNS. T3 may enhance sympathetic nervous system activity by increasing the number of β-adrenergic receptors in heart muscle and the generation of intracellular second messengers such as cyclic adenosine monophosphate (cAMP).