Clinical Note

Increased blood cholesterol (hypercholesterole-mia) is typically found in hypothyroidism. Thyroid hormones reduce cholesterol in the plasma of normal subjects and restore blood concentrations of cholesterol to normal in hypothyroid subjects. Hypercholesterolemia in hypothyroid subjects results from decreased ability to excrete cholesterol in bile rather than overproduction of cholesterol. In fact, cholesterol synthesis is impaired in the hypothyroid individual. T3 may facilitate hepatic excretion of cholesterol by increasing the abundance of low-density lipoprotein (LDL) receptors in hepatocyte membranes, thereby enhancing uptake of cholesterol from the blood.

Lipid Metabolism

Because glucose is the major precursor for fatty acid synthesis in both liver and fat cells, it should not be surprising that optimal amounts of thyroid hormone are necessary for lipogenesis in these cells. Once again the primary determinant of lipogenesis is not T3, but, rather, the amount of available carbohydrate or insulin (see Chapter 41), with thyroid hormone acting as a gain control. Similarly, mobilization of fatty acids from storage depots in adipocytes is compromised in the thyroid-deficient subject and increased above normal when thyroid hormones are present in excess. Once again, T3 amplifies physiologic signals for fat mobilization without itself acting as such a signal.

Nitrogen Metabolism

Body proteins are constantly being degraded and resynthesized. Both synthesis and degradation of protein are slowed in the absence of thyroid hormones; conversely, both are accelerated by thyroid hormone. In the presence of excess T4 or T3, the effects of degradation predominate, and severe catabolism of muscle often results. In hyperthyroid subjects body protein mass decreases despite increased appetite and ingestion of dietary proteins. With thyroid deficiency there is a characteristic accumulation of a mucous-like material consisting of protein complexed with hyaluronic acid and chondroitin sulfate in extracellular spaces, particularly in the skin. Because of its osmotic effect, this material causes water to accumulate in these spaces, giving rise to the edema typically seen in hypothyroid individuals and to the name myxedema for hypothyroidism.

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