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      Relationship between total homocysteine, total cholesterol and creatinine levels in overt hypothyroid patients

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          Abstract

          Hypothyroidism is associated with an increased risk for cardiovascular disease, which can not be fully explained by the atherogenic lipid profile, particularly total cholesterol and LDL-C, and other pathogenic factors may be involved. Plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular disease and accelerated atherosclerosis. The aim of this study was to investigate the serum total homocysteine (tHcy) levels and its relation to total cholesterol, creatinine and thyroid hormones fT3, fT4 and TSH levels in overt hypothyroid patients compared to control subjects. In this study thirty recently diagnosed, non-treated overt hypothyroid patients (f=27, m=3) and twenty normal volunteers control (f=18, m=2) were included and subjected to determination of serum tHcy by enzyme immunoassay (EIA) technique, fT3, fT4 and TSH by Elecsys cobas e 601 analyzer, total cholesterol by enzymatic method and creatinine by kinetic method. The data was statistically analysed by SPSS-10 and p values less than 0.05 were considered significant.Our results showed that there were a significant increase of tHcy, TSH, T.cholesterol and creatinine levels by 113%, 12-folds, 58% and 54%, respectively, and a significant decrease of fT4 and fT3 levels by 49.6% and 56.4% , respectively, in hypothyroid patients than in control group. For tHcy (Mean±SD, 24.45±5.50 μmol/l vs 11.48±3.03 μmol/l, respectively; P < 0.001). tHcy was significantly positively correlated with TSH, creatinine and age and negatively correlated with free thyroxine (fT4) and no significant correlations with fT3 and T.cholesterol. In conclusion, our study confirmed the observation of elevated serum tHcy, T.cholesterol and creatinine in overt hypothyroidism and the presence of an inverse relation between tHcy with fT4 and a positive relation with TSH.

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          Most cited references35

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          Homocysteine metabolism.

          J Selhub (1999)
          Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine, which requires pyridoxal-5'-phosphate. The two pathways are coordinated by S-adenosylmethionine, which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase reaction and as an activator of cystathionine beta-synthase. Hyperhomocysteinemia, a condition that recent epidemiological studies have shown to be associated with increased risk of vascular disease, arises from disrupted homocysteine metabolism. Severe hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in cystathionine beta synthase, methylenetetrahydrofolate reductase, or in enzymes involved in methyl-B12 synthesis and homocysteine methylation. Mild hyperhomocysteinemia seen in fasting conditions is due to mild impairment in the methylation pathway (i.e. folate or B12 deficiencies or methylenetetrahydrofolate reductase thermolability). Post-methionine-load hyperhomocysteinemia may be due to heterozygous cystathionine beta-synthase defect or B6 deficiency. Early studies with nonphysiological high homocysteine levels showed a variety of deleterious effects on endothelial or smooth muscle cells in culture. More recent studies with human beings and animals with mild hyperhomocysteinemia provided encouraging results in the attempt to understand the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. The studies with animal models indicated the possibility that the effect of elevated homocysteine is multifactorial, affecting both the vascular wall structure and the blood coagulation system.
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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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              Correlation between severity of thyroid dysfunction and renal function.

              Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively. In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism. Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log(10)(fT4 post-treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r(2) = 0.81, P < 0.0001) and estimated GFR (0.69, P < 0.0001). The kidney is an important target of thyroid hormone action.
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                Author and article information

                Contributors
                s.bamshmoos@yahoo.com
                malnuzaily@yahoo.com
                am_almeeri@yahoo.com
                sshrmany@yahoo.co.uk
                Journal
                Springerplus
                Springerplus
                SpringerPlus
                Springer International Publishing (Cham )
                2193-1801
                30 August 2013
                30 August 2013
                2013
                : 2
                : 423
                Affiliations
                [ ]Haematology Department, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen
                [ ]Biochemistry Department, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen
                [ ]Haematology Department, Kuwait University Hospital, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen
                [ ]Department of Nutrition and Dietetics, Faculty of medicine and health sciences, Metabolism and Genomic Programme, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia
                Article
                493
                10.1186/2193-1801-2-423
                3766507
                24024107
                cc15d82d-6df2-4807-b0ba-68e99843897a
                © Bamashmoos et al.; licensee Springer. 2013

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 June 2013
                : 23 August 2013
                Categories
                Research
                Custom metadata
                © The Author(s) 2013

                Uncategorized
                hypothyroidism,homocysteine,cardiovascular disease,atherosclerosis,cholesterol,creatinine,thyroxine,triiodothyronine,thyroid stimulating hormone

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