Thyroid replacement therapy and its influence on postheparin plasma lipases and apolipoprotein-B metabolism in hypothyroidism.

T4 replacement at 150 micrograms/day in a group of six hypothyroid subjects led to the development of a euthyroid state and produced a fall in the cholesterol content of plasma and low and high density lipoproteins (LDL and HDL). The effect of T4 on apolipoprotein-B (apoB) metabolism was followed using radioiodinated very low density lipoprotein1 (VLDL1; 60-400 Svedberg units) and VLDL2 (20-60 Svedberg units). The pretreatment plasma concentration of VLDL1 apoB and its rates of synthesis and catabolism were similar to those in normal subjects. VLDL2 apoB was synthesized at a supranormal rate in hypothyroid subjects, and this led to a doubling of its circulating mass. Treatment did not significantly alter the kinetics of apoB in either VLDL1 or VLDL2. The concentration of intermediate density lipoprotein (IDL) apoB in untreated hypothyroids was 170% of normal and fell during T4 treatment due to stimulation of conversion of LDL (from 0.46 +/- 0.14 to 0.91 +/- 0.30 pools/day; mean +/- SD; P < 0.01). Direct IDL apoB clearance was not altered by treatment, whereas the fractional catabolic rate of LDL increased 76% (from 0.17 +/- 0.06 to 0.27 +/- 0.07 pools/day), leading to a 36% decrement in LDL mass. The stimulation of IDL to LDL conversion during therapy was probably due to a 3-fold increase in hepatic lipase activity (P < 0.02). This change together with the known effects of T4 on LDL receptors largely explained the lipoprotein abnormality in hypothyroidism and the effects of replacement therapy.

[1]  H. Lithell,et al.  Serum lipoprotein and apolipoprotein concentrations in patients with hyperthyroidism and the effect of treatment with carbimazole. , 2009, Acta medica Scandinavica.

[2]  A. Salter,et al.  Effects of hypothyroidism and high-fat feeding on mRNA concentrations for the low-density-lipoprotein receptor and on acyl-CoA:cholesterol acyltransferase activities in rat liver. , 1991, The Biochemical journal.

[3]  J. Auwerx,et al.  Alterations in thyroid status modulate apolipoprotein, hepatic triglyceride lipase, and low density lipoprotein receptor in rats. , 1990, Endocrinology.

[4]  M. Taskinen,et al.  Effect of Insulin Therapy on Metabolic Fate of Apolipoprotein B–Containing Lipoproteins in NIDDM , 1990, Diabetes.

[5]  G. Coetzee,et al.  The LDL receptor , 1990 .

[6]  J. Fruchart,et al.  Apolipoprotein B metabolism in homozygous familial hypercholesterolemia. , 1989, Journal of lipid research.

[7]  F. Karpe,et al.  Lipoprotein metabolism in hepatic lipase deficiency: studies on the turnover of apolipoprotein B and on the effect of hepatic lipase on high density lipoprotein. , 1988, Journal of lipid research.

[8]  A. Salter,et al.  Interactions of triiodothyronine, insulin and dexamethasone on the binding of human LDL to rat hepatocytes in monolayer culture. , 1988, Atherosclerosis.

[9]  M. Taskinen,et al.  7 Enzymes involved in triglyceride hydrolysis , 1987 .

[10]  P. de Knijff,et al.  A rapid micromethod for apolipoprotein E phenotyping directly in serum. , 1987, Journal of lipid research.

[11]  P. D. de Moor,et al.  Changes in the distribution and composition of high-density lipoproteins in primary hypothyroidism. , 1985, Metabolism: clinical and experimental.

[12]  C. Packard,et al.  Metabolism of apolipoprotein B in large triglyceride-rich very low density lipoproteins of normal and hypertriglyceridemic subjects. , 1984, The Journal of clinical investigation.

[13]  P. Nilsson-ehle,et al.  Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations. , 1983, Acta endocrinologica.

[14]  P. Nilsson-ehle,et al.  Experimental Hyperthyroidism in Man: Effects on Plasma Lipoproteins, Lipoprotein Lipase and Hepatic Lipase , 1983, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[15]  I. Goldberg,et al.  Lipoprotein metabolism during acute inhibition of hepatic triglyceride lipase in the cynomolgus monkey. , 1982, The Journal of clinical investigation.

[16]  J. Little,et al.  Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. , 1982, Atherosclerosis.

[17]  P. Nilsson-ehle,et al.  Reversal of decreased hepatic lipase and lipoprotein lipase activities after treatment of hypothyroidism , 1982, European journal of clinical investigation.

[18]  A. Soutar,et al.  Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Grundy,et al.  Cholesterol metabolism in hypothyroidism and hyperthyroidism in man. , 1981, Journal of lipid research.

[20]  H. Lithell,et al.  Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein‐lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy , 1981, European journal of clinical investigation.

[21]  B. Lewis,et al.  Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism: in vivo and in vitro studies in man , 1980, European journal of clinical investigation.

[22]  E. Nikkilä,et al.  Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein2 in man. , 1980, Atherosclerosis.

[23]  M. Kashyap,et al.  A rapid and simple method for measurement of total protein in very low density lipoproteins by the Lowry assay. , 1980, Journal of lipid research.

[24]  M. Caslake,et al.  The composition of low-density lipoprotein and very-low-density lipoprotein subfractions in primary hypothyroidism and the effect of hormone-replacement therapy. , 1979, Clinical science.

[25]  R. Havel,et al.  The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. , 1955, The Journal of clinical investigation.

[26]  M. Taskinen,et al.  Lipoproteins, lipolytic enzymes, and hormonal status in hypothyroid women at different levels of substitution. , 1988, The Journal of clinical endocrinology and metabolism.

[27]  E. Man,et al.  The significance of serum cholesterol in thyroid disease. , 1950, The Journal of clinical investigation.