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      LDL in patients with subclinical hypothyroidism shows increased lipid peroxidation

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          Abstract

          Background

          Population-based studies have demonstrated that subclinical hypothyroidism (SCH) is an independent risk factor for atherosclerosis (OR = 1.9). However, this connection cannot be entirely explained by dyslipidemia accompanied by SCH. Lipid peroxidation also plays an important role in the development of atherosclerosis. In this study, we aimed to evaluate oxidative stress in SCH patients, as measured according to concentrations of hydroxy-octadecadienoic acids (HODEs) and hydroxy-eicosatetraenoic acids (HETEs) in both plasma and low density lipoproteins (LDL).

          Subjects and methods

          The concentrations of HODEs and HETEs in both LDL and plasma were examined in euthyroid ( n = 10), mild SCH (4.5 ≤ TSH <10 mU/L, n = 10), and significant SCH (TSH ≥ 10 mU/L, n = 10) subjects, using a liquid chromatograph-electrospray ionization- mass spectrometer. Then, we explored the relationship among LDL oxidation, TSH levels, and carotid intima-media thickness (IMT), a biomarker of subclinical atherosclerosis.

          Results

          Serum LDL-C levels and mean-IMT in the significant SCH group were higher than in the euthyroid group ( p < 0.05). The HODE and HETE concentrations clearly increased in the significant SCH patients compared with the euthyroid subjects, but there was no difference between the mild SCH and euthyroid groups. Among all subjects, linear and significant positive correlations were identified between TSH and mean-IMT after adjustment for confounding factors (r = 0.480, p = 0.018). Both 9-HODE (r = 0.376, p = 0.041) and 13-HODE (r = 0.447, p = 0.013) in LDL were linearly and positively correlated with TSH. The concentrations of HODEs (both 9-HODE and 13-HODE) in LDL were much higher in the thickened IMT group than in the normal IMT group ( p = 0.017 and 0.015, respectively). HODEs in LDL were also positively associated with mean-IMT.

          Conclusions

          Our findings showed that lipid peroxidation was higher in the significant SCH patients than in the euthyroid subjects, which suggested that qualitative as well as quantitative changes in serum lipids resulting from SCH may add to atherosclerosis risk.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12944-015-0092-4) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

          Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.
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            The Colorado thyroid disease prevalence study.

            The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. Cross-sectional study. Participants in a statewide health fair in Colorado, 1995 (N = 25 862). Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.
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              Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.

              Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial. To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women. Population-based cross-sectional study. A district of Rotterdam, The Netherlands. Random sample of 1149 women (mean age +/- SD, 69.0 +/- 7.5 years) participating in the Rotterdam Study. Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result. Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took beta-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease. Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.
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                Author and article information

                Contributors
                gaoling1@medmail.com.cn
                +86-531-68776375 , doctorxuchao@163.com
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                25 August 2015
                25 August 2015
                2015
                : 14
                : 95
                Affiliations
                [ ]Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021 China
                [ ]Department of gynaecology and obstetrics, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021 China
                [ ]Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021 China
                [ ]Clinical Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021 China
                [ ]Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021 China
                [ ]Institute of Endocrinology and metabolism, Shandong Academy of Clinical Medicine, 324, Jing 5 Rd, Jinan, Shandong China
                [ ]Department of endocrinology, Shanghai Second People’s Hospital, Shanghai, 250021 China
                [ ]Department of endocrinology, Shuguang Hospital Baoshan Branch, Shanghai, 250021 China
                [ ]Department of Health Care, Qianfoshan Hospital Affiliated to Shandong University, Jinan, 250014 China
                Article
                92
                10.1186/s12944-015-0092-4
                4548906
                26302822
                867f5331-a4a6-446f-be88-1c1454e147bc
                © Zha et al. 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 March 2015
                : 6 August 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Biochemistry
                subclinical hypothyroidism,oxidative stress,low density lipoproteins
                Biochemistry
                subclinical hypothyroidism, oxidative stress, low density lipoproteins

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