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Thyroid Peroxidase Antibody Is Associated with Plasma Homocysteine Levels in Patients with Graves’ Disease

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Thyroid Peroxidase Antibody Is Associated with Plasma Homocysteine Levels in Patients with Graves’ Disease Published online: 2018-07-02 Article Thieme Li Fang et al. Thyroid Peroxidase Antibody is … Exp Clin Endocrinol Diabetes 2018; 00: 00–00 Thyroid Peroxidase Antibody is Associated with Plasma Homocysteine Levels in Patients with Graves’ Disease Authors Fang Li1 * , Gulibositan Aji1 * , Yun Wang2, Zhiqiang Lu1, Yan Ling1 Affiliations ABSTRACT 1 Department of Endocrinology and Metabolism, Zhong- Purpose Homocysteine is associated with cardiovascular, shan Hospital, Fudan University, Shanghai, China inflammation and autoimmune diseases. Previous studies have 2 Department of Endocrinology and Metabolism, the shown that thyroid peroxidase antibody is associated with ho- Second Hospital of Shijiazhuang City, Shijiazhuang, mocysteine levels in hypothyroidism. The relationship between Hebei Province, China thyroid antibodies and homocysteine in hyperthyroidism re- mains unclear. In this study, we aimed to investigate the asso- Key words ciation of thyroid antibodies with homocysteine in patients human, cardiovascular risk, hyperthyroidism with Graves’ disease. Methods This was a cross-sectional study including 478 received 07.04.2018 Graves’ disease patients who were consecutively admitted and revised 10.05.2018 underwent radioiodine therapy. Homocysteine, thyroid hor- accepted 14.06.2018 mones, thyroid antibodies, glucose and lipids were measured. Results Patients with homocysteine levels above the median Bibliography were older and had unfavorable metabolic parameters com- DOI https://doi.org/10.1055/a-0643-4692 pared to patients with homocysteine levels below the median. Published online: 2.7.2018 Thyroglobulin antibody or thyroid peroxidase antibody was Exp Clin Endocrinol Diabetes 2020; 128: 8–14 associated with homocysteine levels (β = 0.56, 95 %CI 0.03- © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · 1.08, p = 0.04; β = 0.75, 95 %CI 0.23-1.27, p = 0.005). The rela- New York tionship between thyroid peroxidase antibody and homocyst- ISSN 0947-7349 eine remained significant when additionally adjusting for free triiodothyronine (β = 0.76, 95 %CI 0.24-1.28, p = 0.004). The Correspondence presence of a homocysteine level above the median increased Yan Ling, MD & PhD significantly with increasing thyroid peroxidase antibody quar- Department of Endocrinology and Metabolism tiles in the logistic regression (OR = 1.74, 95 %CI 1.27-2.39, P Zhongshan Hospital for trend = 0.001). Homocysteine levels increased significantly Fudan University with increasing thyroid peroxidase antibody quartiles No.180 Fenglin Road (p = 0.005). Thyroid peroxidase antibody had no significant ef- Downloaded by: Thieme E-Books & E-Journals. Copyrighted material. 200032 Shanghai fect on other traditional cardiovascular risk factors. China Conclusions Thyroid peroxidase antibody is independently Tel.: + 86/139/16937 572, Fax: + 86/21/64166 743 and positively associated with homocysteine levels in patients [email protected] with Graves’ disease. Thyroid peroxidase antibody may be as- sociated with the cardiovascular risk of patients with Graves’ disease through its effect on homocysteine. increased left ventricular mass, exercise intolerance and angina Introduction pectoris [1]. Complications include atrial fibrillation with its risk of Thyroid hormones have a significant impact on heart function. Pa- stroke, and high output heart failure. Subclinical hyperthyroidism tients with thyroid disease are at high risk of cardiovascular diseas- patients also have an increased risk of developing atrial fibrillation es. In hyperthyroidism, the cardiovascular effects include an in- [2, 3]. Even individuals with high normal thyroid function have an crease in resting heart rate, blood volume, myocardial contractili- increased risk of atrial fibrillation as well as for atherosclerosis and ty, and ejection fraction, systolic hypertension, systolic murmurs, myocardial infarction [4–6]. On the other hand, thyroid hormone deficiency results in lower heart rate and weakening of myocardial * Equal contributors contraction and relaxation [7]. 8 Li F et al. Thyroid Peroxidase Antibody is Associated with Plasma Homocysteine Levels … Exp Clin Endocrinol Diabetes 2020; 128: 8–14 Homocysteine (Hcy), which is a sulfhydryl-containing amino a positive TRAb, an elevated radioactive iodine uptake and a dif- acid, is an intermediate product in the normal biosynthesis of the fused thyroid enlargement on ultrasound and isotope scanning. amino acids methionine and cysteine [8]. A large amount of stud- ies have shown that Hcy is an independent risk factor of cardiovas- Anthropometric and laboratory measurements cular diseases [9–12]. Immune activation and inflammation may Medical history, medication information and smoking status were be the cause of hyperhomocysteineamia. Recent study has indicat- collected from the medical records. Height and weight were meas- ed that there may be a bi-directional link between Hcy and immu- ured using a wall-mounted stadiometer with patients wearing light no-inflammatory activation, in which immuno-inflammatory acti- clothing and no shoes. Body mass index (BMI) was calculated as vation may contribute to Hcy increase, and Hcy, in its turn, may act weight (kg)/height2 (m2). Systolic blood pressure (SBP) and dias- as a pro-inflammatory and immuno-stimulating molecule puta- tolic blood pressure (DBP) were measured using a mercury sphyg- tively cooperating to the injury of the disease-specific target organs momanometer on the right arm of subjects in a seated position [13]. A positive relationship was found between the concentration after a rest for at least 5 min. Waist circumference was measured of Hcy and some bio-humoral parameters of inflammation, such at the midway between the lowest rib and the iliac crest with the as the circulating levels of soluble receptors for different cytokines, subject standing. Hip circumference was measured around the wid- C-reactive protein (CRP) and adhesion moleculars [14–16]. An as- est portion of the buttocks, with the tape parallel to the floor. sociation also exists between the level of Hcy and the accumulated Waist-to-hip ratio (WHR) was calculated as waist circumference disease activity [14]. (m)/hip circumference (m). Autoimmune thyroid disease is a cluster of autoimmune diseas- Hypertension was defined as SBP ≥ 140 mmHg or es which are commonly seen in clinic. A study has shown that Hcy DBP ≥ 90 mmHg or current use of medication for hypertension. Di- level is higher in hypothyroid patients compared to those euthy- abetes mellitus (DM) was defined according to the American Dia- roid patients [17]. In patients with iatrogenic hypothyroidism, betes Association Guideline [20], or current use of medication for those with Hashimoto’s thyroiditis have significant higher Hcy lev- diabetes. Hyperlipidemia was defined as total cholesterol els than those without Hashimoto’s thyroiditis [18]. There are sig- (TC) ≥ 5.2 mmol/L, triglycerides (TG) ≥ 1.7 mmol/L or current use nificant abnormally high Hcy levels in thyroid peroxidase antibody of medication for hyperlipidemia. Coronary artery disease and (TPOAb) or thyroglobulin antibody (TGAb) positive subjects [8]. A stroke were defined according to the medical history. recent study indicates that in subclinical hypothyroidism and chron- A morning blood sample was collected after at least 8 h of fast- ic autoimmune thyroiditis patients with elevated TPOAb, when ac- ing. Assay for fasting plasma glucose (FPG), 2-h postprandial plas- companied by increased Hcy, may be taken to indicate the pres- ma glucose (2hPPG), TC, TG, high density lipoprotein cholesterol ence of clinically unrecognized coronary heart disease [19]. All (HDL-C) and CRP were measured by a model 7600 automated bio- these studies have shown that autoimmune thyroid disease with analyzer (Hitachi, Tokyo, Japan). The level of low density lipopro- or without hypothyroidism has an elevated Hcy level. TPOAb and tein cholesterol (LDL-C) was calculated by the Friedewald equation. TGAb as the autoimmune markers of autoimmune thyroid disease Hcy was measured using enzymatic cycling assay (Diasys Diagnos- may be associated with the increase of Hcy. tic Systems, Shanghai CO., LTD). Glycosylated hemoglobin (HbA1c) Graves’ disease is one of the common autoimmune thyroid dis- was measured using high performance liquid ion exchange chro- eases which cause hyperthyroidism. Patients with Graves’ disease matography by the Bio-Rad Variant Hemoglobin Testing System have an increased cardiovascular risk, whether their immune-in- (Bio-Rad Laboratories, Hercules, CA). TSH, total triiodothyronine flammatory condition is associated with Hcy levels is not clear. The (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thy- present study aims to investigate the association of Hcy with roxine (FT4), TPOAb, TGAb and TRAb were measured using the TPOAb, TGAb and thyrotrophin receptor antibody (TRAb) in Graves’ electrochemical luminescence method by Modular E170 automat- Downloaded by: Thieme E-Books & E-Journals. Copyrighted material. disease patients. ic electrochemiluminescence analyzer (Roche Diagnostics Ltd., Germany). Materials and Methods Statistical analysis All analysis was performed using SPSS (version 19.0, SPSS Inc, Chi- Study population cago, USA). Two side tests were used. Significance level was defined This was a cross-sectional study including Graves’ disease patients as P < 0.05. Data are expressed as mean ± standard deviation (SD) who were consecutively admitted and underwent radioiodine ther- or median and
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