Serum concentrations of remnant-like particles in hypothyroid patients before and after thyroxine replacement

The Kuma Hospital, Kobe, Hyogo, Japan.
Clinical Endocrinology (Impact Factor: 3.46). 06/2003; 58(5):621-6. DOI: 10.1046/j.1365-2265.2003.01762.x
Source: PubMed


Remnant-like particles (RLPs) reflect chylomicron remnants and very-low-density lipoprotein remnants, which are most likely to be atherogenic particles. To investigate the effect of thyroxine replacement on the metabolism of RLPs in hypothyroidism, we measured serum concentrations of RLPs during an oral fat-loading test in patients with hypothyroidism before and after thyroxine replacement.
Thirteen patients with hypothyroidism, having serum-free thyroxine (FT4) of 4.25 +/- 2.23 pmol/l (mean +/- SD) and TSH of 72.5 +/- 27.7 mU/l, participated in the study. Two-hundred grams of cream containing 32.9% of fat were given to each patient followed by blood draws every 2 h for 8 h. The patients became euthyroid after 3 months of T4 replacement, and the fat-loading tests were then repeated.
Fasting levels of serum total cholesterol and low-density lipoprotein cholesterol were remarkably decreased after T4 therapy (P < 0.0005). Serum high-density lipoprotein cholesterol and triglyceride were also decreased by T4 therapy, not so remarkably but significantly (P < 0.05). Activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) increased 52% and 85%, respectively, from the pretreatment values. Serum concentrations of remnant-like particle cholesterol (RLP-C) and remnant-like particle triglyceride (RLP-TG), measured by immunoseparation assays, significantly decreased from 0.14 +/- 0.03 to 0.09 +/- 0.03 mmol/l (P < 0.0005) and from 0.19 +/- 0.11-0.11 +/- 0.07 mmol/l (P < 0.01), respectively. In the fat-loading test, serum low-density lipoprotein cholesterol concentrations were not changed, while serum RLPs concentrations were increased and remained high throughout the test, with the peak value at 6 h in a hypothyroid condition. In an euthyroid condition after T4 therapy, the peak values of RLPs were obtained at 4 h, and the concentrations were decreased rapidly. As the result, areas under the curve of serum RLPs were decreased remarkably after T4 therapy.
Hypothyroidism seems to be associated with a decrease in metabolism of serum RLPs. Such altered metabolism of RLPs may be related to the decreased activities of LPL and HTGL and can be corrected by T4 replacement therapy.

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    • "By affecting the metabolism of lipids, hypothyroidism accelerates the process of atherogenesis and elevates cardiovascular risk. Although LDL is widely accepted as the major atherogenic lipoprotein, TG-rich lipoproteins such as chylomicron remnants, whose clearance is reduced in hypothyroidism[18] and very LDL remnants still play an important role in atherogenesis. These remnants are taken up by macrophages in the arterial walls to produce foam cells and thus may be a risk factor for atherosclerosis.[19] "
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    ABSTRACT: Lipid abnormalities in hypothyroidism contribute to the disproportionate increase in cardiovascular risk. A possible relationship between serum level of magnesium (Mg) and calcium (Ca) and cardiovascular disease was recorded. In this work, the possible correlation between lipid profile components and serum cations Ca and Mg was investigated. Matched healthy women were evaluated in a cross-sectional study. All parameters were measured spectrophotometrically. The results showed a significant decrease (P < 0.05) in high-density lipoprotein-cholesterol (HDL-C), total and ionized Mg in hypothyroid patients in comparing with control group. There was a significant increase (P <0.05) in serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and (LDL-C)/(HDL-C) ratio in hypothyroid patients as compared with control group. However, no correlation was found between the cation levels and lipid profile of the studied groups. It can be concluded that patients with hypothyroidism exhibited elevated atherogenic parameters (TC and LDL-C) and high risk of cardiovascular diseases.
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    • "Other qualitative lipid alterations, such as abnormal catabolism of remnant lipoproteins, have been described in overt hypothyroidism [191]. Serum concentrations of remnant-like particle cholesterol were corrected by T4 replacement therapy [191]. The same authors, in a following clinical study, showed similar alterations also in sHT patients, reversed by LT4 replacement in most patients [168]. "
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    ABSTRACT: Endothelial dysfunction represents an important pathway thereby cardiovascular risk factors promote the development and progression of atherosclerosis. Hypothyroidism is associated with an increased cardiovascular risk, and the assessment of endothelium function is recognised an effective tool for the detection of evidence of preclinical cardiovascular alterations. Both vascular smooth muscle cells and endothelium play pivotal roles in modulating vascular tone and both are potential targets of thyroid hormone action. The pathogenesis of the association between endothelial dysfunction and hypothyroidism is complex and still not well established. The presence of traditional and emerging risk factors may contribute to the development of endothelium impairment, generating a chronic state of injury that triggers abnormal endothelial response. Levothyroxine replacement therapy is currently used for restoring euthyroidism and improving cardiovascular risk of hypothyroid patients. The decision to treat patients with subclinical hypothyroidism should depend on the presence of risk factors, rather than on a TSH threshold. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events, especially in subclinically hypothyroid patients, remains to be elucidated. Large multicenter, placebo-controlled prospective trials are necessary to address the issue. The article also discusses recent patents in this field.
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