Cell Membranes. One of the enzymes that increases its activity in response to thyroid hormone is Na+-K+-ATPase. This in turn increases the rate of transport of both sodium and potassium ions through the cell membranes of some tissues. Because this process uses energy and increases the amount of heat produced in the body, it has been suggested that this might be one of the mechanisms by which thyroid hormone increases the body's metabolic rate. In fact, thyroid hormone also causes the cell membranes of most cells to become leaky to sodium ions, which further activates the sodium pump and further increases heat production.
Thyroid hormone has both general and specific effects on growth. For instance, it has long been known that thyroid hormone is essential for the metamorphic change of the tadpole into the frog.
In humans, the effect of thyroid hormone on growth is manifest mainly in growing children. In those who are hypothyroid, the rate of growth is greatly retarded. In those who are hyperthyroid, excessive skeletal growth often occurs, causing the child to become considerably taller at an earlier age. However, the bones also mature more rapidly and the epiphyses close at an early age, so that the duration of growth and the eventual height of the adult may actually be shortened.
An important effect of thyroid hormone is to promote growth and development of the brain during fetal life and for the first few years of postnatal life. If the fetus does not secrete sufficient quantities of thyroid hormone, growth and maturation of the brain both before birth and afterward are greatly retarded, and the brain remains smaller than normal. Without specific thyroid therapy within days or weeks after birth, the child without a thyroid gland will remain mentally deficient throughout life. This is discussed more fully later in the chapter.
Effects of Thyroid Hormone on Specific Bodily Mechanisms
Stimulation of Carbohydrate Metabolism. Thyroid hormone stimulates almost all aspects of carbohydrate metabolism, including rapid uptake of glucose by the cells, enhanced glycolysis, enhanced gluconeogenesis, increased rate of absorption from the gastrointestinal tract, and even increased insulin secretion with its resultant secondary effects on carbohydrate metabolism. All these effects probably result from the overall increase in cellular metabolic enzymes caused by thyroid hormone.
Stimulation of Fat Metabolism. Essentially all aspects of fat metabolism are also enhanced under the influence of thyroid hormone. In particular, lipids are mobilized rapidly from the fat tissue, which decreases the fat stores of the body to a greater extent than almost any other tissue element. This also increases the free fatty acid concentration in the plasma and greatly accelerates the oxidation of free fatty acids by the cells.
Effect on Plasma and Liver Fats. Increased thyroid hormone decreases the concentrations of cholesterol, phospholipids, and triglycerides in the plasma, even though it increases the free fatty acids. Conversely, decreased thyroid secretion greatly increases the plasma concentrations of cholesterol, phospholipids, and triglycerides and almost always causes excessive deposition of fat in the liver as well. The large increase in circulating plasma cholesterol in prolonged hypothyroidism is often associated with severe atherosclerosis, discussed in Chapter 68.
One of the mechanisms by which thyroid hormone decreases the plasma cholesterol concentration is to increase significantly the rate of cholesterol secretion in the bile and consequent loss in the feces. A possible mechanism for the increased cholesterol secretion is that thyroid hormone induces increased numbers of low-density lipoprotein receptors on the liver cells, leading to rapid removal of low-density lipoproteins from the plasma by the liver and subsequent secretion of cholesterol in these lipoproteins by the liver cells.
Increased Requirement for Vitamins. Because thyroid hormone increases the quantities of many bodily enzymes and because vitamins are essential parts of some of the enzymes or coenzymes, thyroid hormone causes increased need for vitamins. Therefore, a relative vitamin deficiency can occur when excess thyroid hormone is secreted, unless at the same time increased quantities of vitamins are made available.
Increased Basal Metabolic Rate. Because thyroid hormone increases metabolism in almost all cells of the body, excessive quantities of the hormone can occasionally increase the basal metabolic rate 60 to 100 per cent above normal. Conversely, when no thyroid hormone is produced, the basal metabolic rate falls almost to one-half normal. Figure 76-6 shows the approximate relation between the daily supply of thyroid hormones and the basal metabolic rate. Extreme amounts of the hormones are required to cause very high basal metabolic rates.
Decreased Body Weight. Greatly increased thyroid hormone almost always decreases the body weight,
Thyroid hormones (ug/day)
Thyroid hormones (ug/day)
Approximate relation of daily rate of thyroid hormone (T4 and T3) secretion to the basal metabolic rate.
and greatly decreased hormone almost always increases the body weight; these effects do not always occur, because thyroid hormone also increases the appetite, and this may counterbalance the change in the metabolic rate.
Effect of Thyroid Hormones on the Cardiovascular System Increased Blood Flow and Cardiac Output. Increased metabolism in the tissues causes more rapid utilization of oxygen than normal and release of greater than normal quantities of metabolic end products from the tissues. These effects cause vasodilation in most body tissues, thus increasing blood flow. The rate of blood flow in the skin especially increases because of the increased need for heat elimination from the body. As a consequence of the increased blood flow, cardiac output also increases, sometimes rising to 60 per cent or more above normal when excessive thyroid hormone is present and falling to only 50 per cent of normal in very severe hypothyroidism.
Increased Heart Rate. The heart rate increases considerably more under the influence of thyroid hormone than would be expected from the increase in cardiac output. Therefore, thyroid hormone seems to have a direct effect on the excitability of the heart, which in turn increases the heart rate. This effect is of particular importance because the heart rate is one of the sensitive physical signs that the clinician uses in determining whether a patient has excessive or diminished thyroid hormone production.
Increased Heart Strength. The increased enzymatic activity caused by increased thyroid hormone production apparently increases the strength of the heart when only a slight excess of thyroid hormone is secreted. This is analogous to the increase in heart strength that occurs in mild fevers and during exercise. However, when thyroid hormone is increased markedly, the heart muscle strength becomes depressed because of long-term excessive protein catabolism. Indeed, some severely thyrotoxic patients die of cardiac decompensation secondary to myocar-dial failure and to increased cardiac load imposed by the increase in cardiac output.
Normal Arterial Pressure. The mean arterial pressure usually remains about normal after administration of thyroid hormone. Because of increased blood flow through the tissues between heartbeats, the pulse pressure is often increased, with the systolic pressure elevated in hyperthyroidism 10 to 15 mm Hg and the diastolic pressure reduced a corresponding amount.
Increased Respiration. The increased rate of metabolism increases the utilization of oxygen and formation of carbon dioxide; these effects activate all the mechanisms that increase the rate and depth of respiration.
Increased Gastrointestinal Motility. In addition to increased appetite and food intake, which has been discussed, thyroid hormone increases both the rates of secretion of the digestive juices and the motility of the gastrointestinal tract. Hyperthyroidism often results in diarrhea. Lack of thyroid hormone can cause constipation.
Excitatory Effects on the Central Nervous System. In general, thyroid hormone increases the rapidity of cerebration but also often dissociates this; conversely, lack of thyroid hormone decreases this function. The hyper-thyroid individual is likely to have extreme nervousness and many psychoneurotic tendencies, such as anxiety complexes, extreme worry, and paranoia.
Effect on the Function of the Muscles. Slight increase in thyroid hormone usually makes the muscles react with vigor, but when the quantity of hormone becomes excessive, the muscles become weakened because of excess protein catabolism. Conversely, lack of thyroid hormone causes the muscles to become sluggish, and they relax slowly after a contraction.
Muscle Tremor. One of the most characteristic signs of hyperthyroidism is a fine muscle tremor. This is not the coarse tremor that occurs in Parkinson's disease or in shivering, because it occurs at the rapid frequency of 10 to 15 times per second. The tremor can be observed easily by placing a sheet of paper on the extended fingers and noting the degree of vibration of the paper. This tremor is believed to be caused by increased reactivity of the neuronal synapses in the areas of the spinal cord that control muscle tone. The tremor is an important means for assessing the degree of thyroid hormone effect on the central nervous system.
Effect on Sleep. Because of the exhausting effect of thyroid hormone on the musculature and on the central nervous system, the hyperthyroid subject often has a feeling of constant tiredness, but because of the excitable effects of thyroid hormone on the synapses, it is difficult to sleep. Conversely, extreme somnolence is characteristic of hypothyroidism, with sleep sometimes lasting 12 to 14 hours a day.
Effect on Other Endocrine Glands. Increased thyroid hormone increases the rates of secretion of most other endocrine glands, but it also increases the need of the tissues for the hormones. For instance, increased thy-roxine secretion increases the rate of glucose metabolism everywhere in the body and therefore causes a corresponding need for increased insulin secretion by the pancreas. Also, thyroid hormone increases many metabolic activities related to bone formation and, as a consequence, increases the need for parathyroid hormone. Thyroid hormone also increases the rate at which adrenal glucocorticoids are inactivated by the liver. This leads to feedback increase in adrenocorti-cotropic hormone production by the anterior pituitary and, therefore, increased rate of glucocorticoid secretion by the adrenal glands.
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