Hypothyroidism Cholesterol levels

Increased cholesterol levels in serum are found in patients suffering from chronic hepatitis, atherosclerosis (deposit of fat in arteries of heart) and hypothyroidism,... 

Since hypercholesterolemia (in particular, LDL cholesterol) increases the risk of CHD, it seems reasonable to lower cholesterol levels in patients whose levels put them at risk. Before treatment, other risk factors such as hypertension, cigarette smoking, obesity, and glucose intolerance need to be evaluated and corrected. Disorders that exacerbate hyperlipoproteinemia (e.g., chronic ethanol abuse, hypothyroidism, diabetes mellitus) need to be treated before lipid-lowering measures are taken (discussed earlier. Table 20-7). 

Though the plasma cholesterol level is not significantly altered in non-fasting blood samples, this woman s hypercholesterolaemia should be confirmed on a fasting plasma sample in which her triglyceride and HDL cholesterol should also be measured. Secondary causes of hyperlipidaemia such as hypothyroidism and diabetes mellitus should be excluded. If her plasma triglyceride is normal and she has primary hypercholesterolaemia, a likely diagnosis is familial hypercholesterolaemia (FH). 

TSH levels are increased (overt hypothyroidism). Some authors reported that individuals with TSH values in the upper half of the reference range had a higher mean serum cholesterol level than those with low-normal TSH levels (Michalopoulou et al., 1998). Accordingly, some authorities (National Academy of Clinical Biochemistry) have proposed to lower the upper limit for TSH levels to 2.5mU/l (Baloch et ai, 2003 Wartofsky and Dickey, 2005). This criterion has been criticized because it would result in an overdiagnosis of subciinicai hypothyroidism and an increase in the number of patients on unnecessary replacement therapy (Surks et al., 2005 Dlez et al., 2005). 

A characteristic sign of hypothyroidism is a decrease in metabolic rate, with a reduction in calorigenic effect and defective thermoregulation. The elevated serum cholesterol level seen in hypothyroidism is the result of a decrease in cholesterol degradation that exceeds the decrease in cholesterol biosynthesis it reflects a... 

The effects of thyroid hormone on cholesterol metabolism have been studied in bile fistula rats Such preparations exhibit an inverse relationship between serum cholesterol levels and biliary cholesterol concentrations. The level of biliary cholesterol is directly related to thyroid activity, and the biliary excretion of cholesterol increases in the hyperthyroid state and decreases in the hypothyroid state (2,3). 

Thyroid hormones have long been known to affect lipid metabolism. Thyroxine undoubtedly controls cholesterol metabolism serum cholesterol levels are markedly increased in hypothyroidism and decreased in hyperthyroidism. There are various ways by which thyroxine could cause cholesterol to accumulate in blood direct stimulation of the pathway involved in cholesterol biosynthesis block of cholesterol use for further biosynthesis indirect stimulation of cholesterol synthesis by acceleration of pathways that provide precursors of coenzymes needed for cholesterol synthesis and indirect stimulation of cholesterol synthesis by blocking pathways that use those precursors involved in cholesterol synthesis. The exact mechanism by which thyroxine induces the accumulation of cholesterol in serum needs to be elucidated. The effect of thyroid hormones on blood cholesterol must be understood because hypothyroidism is known to enhance the development of experimental arteriosclerosis in animals. 

In contrast to hypothyroids who have low serum cholesterol levels (120-125 mg/100 ml), patients with myxedema have blood cholesterol levels ranging between 260 and 400 mg/100 ml. The interrelationship between the thyroid hormone and cholesterol metabolism needs to be clarified further. The increased level of serum cholesterol observed in hypothyroids could result either from increased synthesis or from a decreased rate of cholesterol breakdown. Studies of cholesterol and fatty acid synthesis in hyper- and hypothyroid rats have indicated that the absolute levels of the synthesis of both fatty acid and cholesterol increase with the increase in oxygen consumption. Weiss and Marx have shown that in rats thyroid hormone accelerates the conversion of labeled cholesterol to acidic products and the excretion of the labeled products. 

It seems safe to conclude that in hypothyroids the increase in serum cholesterol levels results from a shift in the rate of use versus the rate of synthesis, and that, in spite of low rates of synthesis, cholesterol increases in serum because of the low rate of use. 

It is well estabhshed that serum cholesterol in hypothyroid patients is invariably elevated and then rapidly reduced after thyroid hormone administration. Using radioactive acetate and labeled cholesterol, respectively, it has been demonstrated [173] that both the biosynthesis and the rate of ehmination of cholesterol are lower than normal in hypothyroidism. It has been suggested, therefore, that catabolism of cholesterol is impaired to a greater extent than the biosynthesis of the same, so that hypercholesterolemia is the necessary consequence. Administration of thyroid hormone causes less cholesterol biosynthesis than the oxidative removal of sterols resulting in a reduction of serum cholesterol levels [173]. 

The thyroid appears to be involved in cholesterol metabolism—hyperthyroidism relates to lower serum cholesterol, whereas, hypothyroidism relates to elevated serum cholesterol. In myxedematous or hyperlipe ic a-tlents, thyroid hormone Induced a fall in serum cholesterol level. ... 

The effect of thyroid hormone on the blood cholesterol level is well known (Kritchevsky, I960 Boyd, 1963), According to Byers et al. (1952) and Rosenman et al. (1952), the chief cause of the changes of blood cholesterol in hypothyroid and hyperthyroid states is the altered rate of turnover of cholesterol. Despite the increased level of blood cholesterol in hypothyroidism, the synthesis of cholesterol is decreased (Gould et al., 1955 Lipsky et al., 1955 Gould, 1959). In the steady state this depressed rate of synthesis of cholesterol thus must be balanced by a corresponding decrease in the elimination of cholesterol. It seems reasonable to assume that the chief cause of the increased retention of cholesterol should be an impairment of the elimination,... 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

The hypothyroid condition is associated with increased blood lipid levels, which can be treated using statins or cholesterol binding resins such as colestyramine. 

Apohpoprotein E2 occurs in about 1% of the population in North America, and homozygotic subjects for this isoform exhibit P-VLDL. However, overt type III hyperlipoproteinemia occurs in only one to two persons per thousand in the general population (LRC prevalence study), indicating that the occurrence of the defective alleles is necessary but not sufficient to produce clinical type III hyperlipoproteinemia. The development of overt hyperlipoproteinemia in these patients is modulated by genetic, hormonal, or environmental factors—such as hypothyroidism, glucose intolerance, decreased estrogen levels after menopause, obesity, and diet— that may lead to decreased LDL receptor activity, increased VLDL production, or increased plasma cholesterol... 

A complete fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides should be done in all CKD patients. Lipoprotein levels may be inflnenced by several factors inclnding GFR and proteinuria. It is recommended that these patients have their lipid profile assessed more freqnently than in the general popnlation in order to identify abnormahties and treat them early. In patients on hemodialysis the hpid profile shonld be done prior to dialysis or on nondialysis days. Patients shonld also be evalnated for other conditions that are known to cause dyslipidemias (e.g., liver disease and hypothyroidism). 

Hyperlipidaemias are conditions where levels of LDL cholesterol are raised relative to HDL levels. They can be primary or secondary to other conditions such as diabetes or hypothyroidism. About 5% of cases are due to a hereditary condition where there is a deficiency of LDL receptors on cell membranes (familial hyperlipidaemia). 

As the TSH is approximately 20 times the upper limit of the reference range and the serum T is significantly decreased, this woman has severe hypothyroidism. Skeletal and cardiac muscles are involved in the hypothyroid process, causing the release of creatine kinase into the circulation. This, combined with a decrease in the catabolic rate of creatine kinase, will be sufficient to cause the creatine kinase to increase to the levels observed in this case. The aspartate aminotransferase is at the upper end of the reference range and this will fall along with the creatine kinase and cholesterol after a few weeks treatment with thyroxine. In view of the evidence of myocardial ischaemia it is prudent to proceed cautiously in this case with a low dose of thyroxine and gradually increase it in a step-wise manner. 

Increased total and LDL cholesterol, triglycerides and oxidized low-density lipoproteins have been reported in patients with overt hypothyroidism. A TH defect is also associated with significant changes in HDL, with a hypercoagulable state and with elevated C-reactive protein and homocysteine levels, insulin resistance and arterial stiffness. 

Chronic hepatitis was reported in a 58-year-old woman with a history of high blood pressure, hypothyroidism, diabetes, and high cholesterol. The woman had been taking 80 mg of black cohosh extract daily for 1 year along with irbesartan, levothyroxin, simvastatin, and insulin. The liver injury was initially thought to be induced by simvastatin, although discontinuation of simvastatin did not result in a reduction of liver enzyme levels (Pierard et al. 2009). 

Since, in the rat, cholesterol is eliminated largely in the form of bile acids, it was expected that bile acid secretion in bile would be increased in the hyperthyroid state. Early experiments to test this point indicated that biliary bile acid secretion was actually normal or below normal (2,3). These results can be explained in terms of the inadequate analytical procedures then in use. Only cholate secretion was measured, and the levels of cheno-deoxycholate were not taken into account. When both of these bile acids were determined, it was shown that, in the bile fistula rat, the total production of bile acids was about the same in the hyperthyroid as in the euthyroid state, and lower in the hypothyroid state (4). In addition, in the hyperthyroid state, the normal ratio of cholate/chenodeoxycholate was reversed from approximately 3 1 to 1 3—cholic acid synthesis was decreased, and chenodeoxycholic acid synthesis was increased two- to threefold (4). Identical results were obtained in the bile fistula rat treated with noncalorigenic doses of D-tri-iodothyronine (5,6), suggesting that these effects are not necessarily a function of the basal metabolic rate. 

Such observations indicate that the absolute rate of cholesterol synthesis is increased in hyperthyroidism and decreased in hypothyroidism. These findings can be correlated with the alteration in the levels of activity of the enzymes of the hexose monophosphate shunt (an important source of NADPH). The activities of the enzymes of the hexose monophosphate pathway are increased in hyper- and decreased in hypothyroidism. In spite of the considerable interest that such findings generate, their correct interpretation will have to wait until the mechanisms controlling the rate of cholesterol synthesis are adequately understood. 

The effect of thyroid hormones on fatty acid metabolism probably resembles the effect of the hormone on cholesterol metabolism. Fatty acid synthesis increases in hyperthyroidism and decreases in hypothyroidism. In contrast, the rate of oxidation of butyrate is accelerated in hyperthyroidism and decreased in hy-pxthyroidism. The levels of serum phospholipids are increased in hypothyroidism. The mechanism of this metabolic alteration is not known. 

Of the secondary hyperlipidemias those of hypothyroidism and biliary cirrhosis deserve particular attention, since they may show considerable elevation of cholesterol without hyperglyceridemia. In addition, xanthomas may occur in both with long duration. While biliary cirrhosis is characterized by the presence of jaundice, a very low ester cholesterol to free cholesterol ratio, and significant elevation of the phospholipid level, the exclusion of hypothjrroidism is not always as simple and may require appropriate thyroid function tests. 

Iodine. The sole function of iodine in the human body is as a component of the hormones secreted by the thyroid gland. A dietary deficiency of iodine may lead to low levels of these hormones (hypothyroidism), a condition which is often accompanied by high blood cholesterol, and in some cases, atherosclerosis. Studies in Finland have shown that, although the dietary levels of fat are similar throughout the country, there seem to be more cases of cardiovascular diseases in the areas where the rates of goiter (an enlargement of the thyroid due to iodine deficiency) are also high. ... 

This specifity for cholate or its conjugates on cholesterol absorption has also been demonstrated by modification of biliary bile acid composition by hormonal perturbations (see[40]). For example, in hypothyroid rats, there is a diminished biliary output of bile acids[41], and a shift in the ratio of biliary cholate and cheno-deoxycholate. This ratio is approximately 3 1 cholate to cheno-deoxycholate in normal rats and is shifted dramatically (9 1) in hypothyroid rats[42]. As might be expected, this hormonal deficiency results in multiple alterations in overall physiology, among which are hypercholesterolemia and increased absorbability of choles-terol[40]. Conversely, administration of thyroid hormones (L-thyroxine or triiodothyronine) results in diminished levels of biliary cholate, and proportional increases in chenodeoxycholate. 

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