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Thyroid hormone action on intermediary metabolism

Part II: Lipid metabolism in hypo- and hyperthyroidism

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Summary

Despite their enhanced endogenous de novo cholesterol synthesis, hyperthyroid patients exhibit decreased total and low-density lipoprotein (LDL) cholesterol levels in the serum because of a concomitant increase in LDL catabolism, cholesterol excretion by bile and a reduced enterohepatic bile acid circulation. Hypothyroidism exhibits a reduction (1) in the synthesis of cholesterol and (2) in LDL catabolism, whereas cholesterol reabsorption is unchanged or even enhanced. In addition, obese hypothyroid patients showed an increased cholesterol synthesis which is independent of thyroid hormones and which contributes to the observed LDL cholesterolaemia. Thyroid hormones per se have only a minor influence on plasma triglyceride (TG) levels, but they induce an acceleration of TG turnover and chylomicron clearance rate. In addition, the hepatic lipogenic capacity is increased in hyperthyroidism and reduced in hypothyroidism. However, hepatic total and very low-density lipoprotein (VLDL) triglyceride output is decreased by thyroid hormones due to a reduced re-esterification and a simultaneously increased oxidation of newly synthesized fatty acids. Hypothyroid livers, by contrast, reveal an increased VLDL secretion. Despite their reduced lipogenesis, obese hypothyroidism is often accompanied by a hypertriglyceridaemia type III. The simultaneous stimulation of the synthesis of fatty acids, which are still in part converted to TG, and the degradation of TG contributes to the enhanced thermogenesis in hyperthyroid patients. The concentration and turnover of free fatty acids (FFA) are increased in hyperthyroidism, resulting from a thyroid hormone-induced increase in: (1) lipolysis, explained by an increased adipose tissue sensitivity for lipolytic hormones; and (2) oxidation of fatty acids to CO2 as well as to ketone bodies (KB). Accordingly, hyperthyroid patients often show ketonaemia. Hypothyroidism does not significantly affect the serum concentrations of FFA and KB.

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Thyroid hormones are defined as 3,5,3′,5′-tetraiodothyronine (thyroxine-T4) and its deiodinated or non-deiodinated metabolic products providing thyromimetic activity, mainly 3,5,3′-triiodothyronine (T3)

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Müller, M.J., Seitz, H.J. Thyroid hormone action on intermediary metabolism. Klin Wochenschr 62, 49–55 (1984). https://doi.org/10.1007/BF01769663

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