Hypothyroidism results in small dense LDL independent of IRS traits and hypertriglyceridemia

Division of Clinical Biochemistry, Mubarak Al-Kabeer Hospital, Kuwait.
Endocrine Journal (Impact Factor: 2.02). 06/2008; 55(2):381-9. DOI: 10.1507/endocrj.K07E-065
Source: PubMed

ABSTRACT There is evidence of an association between hypothyroidism and coronary heart disease. We decided to look at the relationship between hypothyroidism and LDL subclasses' pattern including small, dense LDL to define a biochemical basis for better management of the CHD risk of these patients. We utilized a case-control design to evaluate differences in lipid parameters between cases and controls. Univariate analysis revealed that many factors were associated with LDL particle size. Binary logistic regression however revealed that only thyroid status and serum triglyceride (TG) levels were independently associated with LDL particle size. Results from this study support an independent association between LDL particle size phenotype and both plasma TG concentrations and thyroid status. After adjusting for TG levels, other insulin resistance syndrome (IRS) traits were not associated with LDL size phenotype, suggesting that the IRS related sdLDL is linked most strongly to alterations in TG levels.

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    ABSTRACT: BACKROUND: Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. METHODS: 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. RESULTS: Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55+/-11,671 vs 0,83+/-1,693mg/dl;p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538;p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients. CONCLUSIONS: Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.
    Lipids in Health and Disease 10/2014; DOI:10.1186/1476-511X-13-158 · 2.31 Impact Factor
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    ABSTRACT: For identification of toxicological modes of action (MOAs) a database (MetaMap(®)Tox) was established containing plasma metabolome consisting of approximately 300 endogenous metabolites. Each five male and female Wistar rats per groups were treated with>500 reference compounds over a period of 28 days. More than 120 specific toxicity patterns of common metabolite changes associated with unique MOAs were established. To establish patterns predictive effects on the thyroid, animals have been treated with reference compounds directly acting on the thyroid hormone formation (such as methimazole, ethylenethiourea) as well as liver enzyme inducers leading to an increased excretion of thyroid hormones and therewith to a secondary response of the thyroid (such as aroclor 1254 and boscalid). Here we present the plasma metabolite changes which form the patterns for direct and indirect effects on the thyroid. It is possible to identify metabolites which are commonly regulated irrespective of an indirect or direct effect on the thyroid as well as groups of metabolites separating both MOAs. By putting the metabolite regulations in the context of affected pathways helps to identify thyroid hormone inhibiting MOAs even when the hormone levels are not consistently changed. E.g., direct thyroid hormone synthesis inhibitors affect some enzymes in the urea cycle, increase the ω-oxidation of fatty acids and decrease glutamate and oxoproline levels, whereas indirect thyroid hormone inhibiting compounds interact with the lipid mediated and liver metabolism.
    Toxicology Letters 12/2013; DOI:10.1016/j.toxlet.2013.12.010 · 3.36 Impact Factor
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    ABSTRACT: Hypothyroidism is a common disorder that confers an increased cardiovascular risk. The most common cause is Hashimoto thyroiditis (HT) but it can also be caused by thyroidectomy and radioiodine therapy. The aim of the study is to examine whether there is a relation between the cause of hypothyroidism and cardiovascular risk. Subjects and methods: The study included 20 patients with Hashimoto thyroiditis and hypothyroidism, 20 patients with post-thyroidectomy hypothyroidism, 20 patients with post-radioiodine hypothyroidism, and 20 age and sex matched controls. In all the studied subjects we determined thyroid function tests; TSH and F.T4, thyroid auto-antibodies; anti-TPO and anti-TG antibodies, carotid intima media thickness (CIMT), flow mediated dilation (FMD) and serum nitric oxide. Results: CIMT showed a trend to be higher in HT group (0.93± 0.08 mm) compared to other causes of hypothyroidism (P = 0.090). Multivariate analysis showed that HT is an independent predictor of CIMT (P = 0.015). FMD was significantly lower in HT group (5.74± 1.33%) compared to post-thyroidectomy (7.16± 1.05%) (P = 0.001), and post-radioiodine therapy (7.34 ±1.34%) (P = 0.000). Multivariate analysis showed that HT is an independent predictor of FMD (P =0.000). NO was significantly higher in hypothyroid patients (125.98 ± 5.03 lM/ml) compared to controls (39.44± 3.63 lM/ml) (P =0.001), both univariate and multivariate analyses showed that NO is an independent predictor of both CIMT and FMD (P = 0.000). Conclusion: To our knowledge, this is the first study to show that Hashimoto thyroiditis is an independent cardiovascular risk factor in clinically hypothyroid patients.
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