Objective: Thyroid dysfunction was found to be more common among women with metabolic syndrome. A cross-sectional analysis showed that subjects with subclinical hypothyroidism (SH) had high prevalence of cardiovascular disease than euthyroid subjects. The objective of the current study is to evaluate the prevalence of metabolic syndrome and cardiovascular risk factors among subclinical Â hypothyroid subjects. Methods: Â Thirty untreated subclinical hypothyroid women and thirty normal healthy subjects were recruited for the study. Fasting blood samples were collected for lipid profile, glucose and insulin level estimation. Results: Fasting plasma glucose, total cholesterol, triglycerides and LDL-cholesterol were found to be significantly increased in SH patients Both systolic and diastolic blood pressures were higher in the patient group. 43.3 percentÂ of the SH patients were found to satisfy the criteria for metabolic syndrome. Conclusion: In our study, subclinical hypothyroidism is significantly associated with metabolic syndrome and its components. Whether this association might be translated into a compounded cardiovascular risk needs to be evaluated by further studies.Key Words: Subclinical hypothyroidism, metabolic syndrome, cardiovascular risk

Pangaluri, Renuka

S, Akila

William, Ebenezer

English

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   Research Article  PREVALENCE OF METABOLIC SYNDROME AND ITS COMPONENTS IN WOMEN WITH SUBCLINICAL HYPOTHYROIDISM RENUKA PANGALURI*, AKILA S, EBENEZER WILLIAM Department of Biochemistry, SRM Medical College Hospital & Research Centre, Kattankulathur, Kancheepuram District-603203, Tamilnadu. Email: rpangaluri@yahoo.com Received: 14 August 2013, Revised and Accepted: 7 September 2013 ABSTRACT Objective: Thyroid dysfunction was found to be more common among women with metabolic syndrome. A cross-sectional analysis showed that subjects with subclinical hypothyroidism (SH) had high prevalence of cardiovascular disease than euthyroid subjects. The objective of the current study is to evaluate the prevalence of metabolic syndrome and cardiovascular risk factors among subclinical  hypothyroid subjects.  Methods:  Thirty untreated subclinical hypothyroid women and thirty normal healthy subjects were recruited for the study. Fas ting blood samples were collected for lipid profile, glucose and insulin level estimation.  Results: Fasting plasma glucose, total cholesterol, triglycerides and LDL-cholesterol were found to be significantly increased in SH patients Both systolic and diastolic blood pressures were higher in the patient group. 43.3% of the SH patients were found to satisfy the criteria for metabolic syndrome.  Conclusion: In our study, subclinical hypothyroidism is significantly associated with metabolic syndrome and its components. Whether this association might be translated into a compounded cardiovascular risk needs to be evaluated by further studies. Keywords: Subclinical hypothyroidism, metabolic syndrome, cardiovascular risk.  INTRODUCTION Subclinical hypothyroidism is defined as an asymptomatic condition with high serum TSH levels and normal free thyroid hormone levels [1]. The rate of progression to frank hypothyroidism has been shown to be 2-5% per year being more prevalent in women and elderly people [2]. Metabolic syndrome is a cluster of risk factors characterized by hypertension, atherogenic dyslipidemia, hyperglycemia, prothrombotic and proinflammatory conditions [3]. Thyroid function affects the parameters causing metabolic syndrome including low density lipoproteins, triglycerides, blood pressure and plasma glucose. A higher prevalence of thyroid disorders is reported in type 2 diabetes mellitus [4]. The prevalence of thyroid dysfunction was reportedly more among women with metabolic syndrome [5, 6].  The prevalence of cardiovascular disease is 2-3 times higher in individuals with metabolic syndrome [7]. A cross-sectional analysis revealed that subjects with subclinical hypothyroidism had a significantly higher prevalence of cardiovascular disease than euthyroid subjects [8].  There is increasing evidence that both metabolic syndrome and subclinical hypothyroidism are associated with an increased cardiovascular risk. Data regarding the relationship between metabolic syndrome and thyroid function is conflicting. Hence, we undertook this study to examine the prevalence of metabolic syndrome among subclinical hypothyroid subjects and also to assess the traditional cardiovascular risk factors in these patients.  MATERIALS AND METHODS Based on their thyroid profile, thirty untreated subclinical hypothyroid subjects and thirty age matched healthy women in the 20-60 years were recruited for the study from SRM Medical College Hospital and Research Centre. Cases with history of overt hypothyroidism, renal disease, cardiac disease, acute infection and liver disease were excluded from the study. The Institutional ethical committee approved the study and a written informed consent was obtained from the subjects. Fasting blood samples were collected. The samples were centrifuged, separated and analyzed using Beckman Coulter autoanalyzer AU400 on the same day of collection. Serum levels of total cholesterol, HDL-C, triglycerides and plasma glucose were measured using enzymatic methods with reagents supplied by Beckman Coulter Inc., USA. Thyroid profile assay for selection of subjects was done by competitive enzyme immunoassay (Automated Immunoassay analyzer -360) from TOSOH Corporation, Japan. Metabolic syndrome was diagnosed when three or more of the following were present: Waist circumference more than 35 inch (women), Blood pressure > 130/85 mm Hg, plasma glucose > 100 mg/dL, triglycerides > 150 mg/dL, HDL-C < 50 mg/dL. Statistical analysis was performed using SPSS software version 17. Student's t-test, chi-square test were used for comparison of qualitative data. Pearson correlation was used for the analysis of p value and correlation for scale variable. p value < 0.05 is considered significant. Data were defined as mean ± SD. RESULTS Clinical and biochemical characteristics of the study groups are given in Table  1. Systolic and diastolic blood pressures in subclinical hypothyroidism patients were significantly higher than values in controls. The two groups did not differ in waist circumference, HDL-cholesterol, insulin levels and HOMA-IR.  Fasting plasma glucose, total cholesterol, triglycerides and LDL-cholesterol levels were significantly higher in SH group than in controls. Table 1. Clinical and biochemical characteristics of the subclinical hypothyroid and control groups Variables Subclinical hypothyroidism group Control group P value Age 37.35±10.26 34.55±9.34 NS BMI 25.1±4.56 24±3.2 NS Serum TSH (µIU/mL) 7.51±1.21 2.23±0.32 <0.01 Serum FT3 (pg/mL) 2.72±0.58 2.43±0.44 NS Serum FT4 (ng/dL) 0.92±0.14 0.82±0.12 NS  Vol 6, Issue 4, 2013                                                                                                                                                                                                   ISSN - 0974-2441                                                                                                                                                                                                 Pangaluri et al. Asian J Pharm Clin Res, Vol 6 Issue 4, 2013, 82-84 83  Waist circumference (cm) 82.8±12.4 81.5±10.2 NS Systolic blood pressure (mm Hg) 127.6±15.8 108.3±9.12 <0.01 Diastolic blood pressure (mm Hg) 81.6±11.16 73.3±6.6 <0.01 Total cholesterol (mg/dL) 172.4±23.9 155.6±21.4 0.002 Triglycerides (mg/dL) 140.5±44.8 94.8±25.2 <0.001 LDL-C (mg/dL) 106.4±21.23 95.2±21.4 <0.05 HDL-C (mg/dL) 43.7±10.3 42.0±8.8 NS Fasting glucose (mg/dL) 112.4±11.25 86.6±5.38 <0.001 Insulin (µIU/mL) 9.04±6.53 10.26±6.87 NS HOMA-IR 2.24±1.58 2.35±1.45 NS Data are expressed as mean ± SD. P value < 0.05 are considered significant.  NS = Not significant Bivariate analysis for metabolic syndrome in patients with subclinical hypothyroidism (Table 2) shows that 33.3% of patients in subclinical hypothyroidism groups have hypertension. A higher percent of SH group had metabolic syndrome than the comparison group (43.3%  vs 6.66%, p=0.001). Dysglycemia is also more prevalent among SH group (53.3% vs 3.33%). Insulin and HOMA-IR did not differ between the groups. Hypertriglyceridemia was more prominent in SH patients.  Table2: Bivariate analysis for metabolic syndrome in patients with subclinical hypothyroidism Variable Subclinical hypothyroidism group Control group Statistical test Metabolic syndrome 43.3% 6.66% X2 = 10.76 P=0.001* Insulin resistance 56.6% 60% X2 = 0.006 P=0.39 Dysglycemia 53.3% 3.33% X2 = 18.5 P=0.001* Waist circumference 43.3% 23.3% X2 = 2.7 P=0.1 Triglycerides 26.6% 3.33% X2 = 6.41 P=0.01* Hypertension 23.3% 3.33% X2 = 5.19 P=0.02* Data are expressed as percent of subjects with abnormal results P value < 0.05 are considered significant.                    Table 3 shows that a positive correlation exists between TSH levels and blood pressure, triglycerides and LDL-cholesterol. Table3: Correlation between TSH and Lipid profile and blood pressure  Systolic BP Diastolic BP Triglycerides LDL-C TSH r=0.369 (p=0.04)* r=0.39  (p=0.03)* r=0.46 (p=0.001)* r=0.84 (p=0.001)* Correlation is significant at P value < 0.05 DISCUSSION In our study, we demonstrated that women with subclinical hypothyroidism have significantly higher prevalence of hypertension, hypercholesterolemia, hypertriglyceridemia and dysglycemia. 43.3% of SH patients are having metabolic syndrome. On examining each component of metabolic syndrome among these patients - 23.3% had hypertension, 53.3% had dysglycemia, 43.3% had higher waist circumference, 26.6% had high triglycerides and 30% had decreased HDL-C levels. These findings are in concurrence with other studies which reported that SH would affect each component of metabolic syndrome including blood pressure and metabolism of carbohydrates and lipids [9, 10].  The thyroid hormones are known to play a role in regulating the synthesis, metabolism and mobilization of lipids. A significant increase in total cholesterol, triglycerides and LDL-C in SH patients in our study is in agreement with previous research [11, 12]. No correlation was found between total cholesterol and thyroid hormone levels whereas a positive correlation exists between TSH and triglycerides. 26.6% of SH patients had hypertriglyceridemia. There is increasing evidence indicating that elevated triglyceride levels are independent risk factors for cardiovascular disease. Hypertriglyceridemia and increased C-reactive protein levels were documented in SH patients, suggesting low grade inflammation and risk factors for developing cardiovascular disease. Our findings concur with recent studies demonstrating that 19-30% patients with SH have hypertriglyceridemia [13]. Subclinical hypothyroid patients in the present study had higher levels of LDL-C which positively correlated with TSH levels. The increase in LDL-C levels may be accompanied by increased formation of oxidised LDL-C contributing to enhanced risk of atherosclerosis [14]. Thyroxine replacement in these patients seems to have a beneficial effect by decreasing cardiovascular mortality by 9-31% [15, 16].  Both systolic and diastolic blood pressure has been found to be significantly increased in subclinical hypothyroid women. TSH levels were found to have a positive correlation with blood pressure. In a large population study, a positive linear association was established between systolic and diastolic arterial pressure and TSH levels [17].  Dysglycemia is more frequent among SH patients (53.3%). Dysglycemia has been characterized by the presence of cardiometabolic risk factors [18].  Insulin and HOMA-IR were not different between the groups. Muscle and adipose tissue are resistant to glucose uptake under the influence of insulin, whereas suppression of lipolysis by insulin is not impaired in hypothyroidism. Insulin resistance in muscle and adipose tissue was observed after stimuli but not in the fasting state. Decreased blood flow to these tissues might be one of the pathogenetic mechanisms for insulin resistance in these patients [19].  CONCLUSION We have shown that subclinical hypothyroidism is significantly associated with metabolic syndrome and its components especially dysglycemia, hypertension and hypertriglyceridemia. The association of subclinical hypothyroidism with metabolic syndrome might result in a compounded cardiovascular risk which needs to be addressed by further studies. Therefore screening and treatment of metabolic syndrome may reduce the cardiovascular risk in these patients. Conflict of interest: None REFERENCES 1. Subclinical Thyroid Disease. Scientific review and guidelines for diagnosis and management. JAMA 2004;291: 228-38. 2. Diez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years, an analysis of nature, course and risk factor for the development of overt thyroid failure. J Clin Endocrinol Metab. 2004;89: 4890-7. 3. Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol. 2006;47: 1093-1100. 4. Nima V Thakkar, Sunita M Jain. Assessment of the metabolic profile in patients of type 2 Diabetes mellitus and hypothyroidism through comet assay. Asian J Pharm Clin Res. 2011;Vol 4(1): 66-71. 5. Gaurav Agarwal, Sudhakar MK, Mohini Singh, Senthil N, Amarabalan Rajendran. The prevalence of thyroid Pangaluri et al. Asian J Pharm Clin Res, Vol 6 Issue 4, 2013, 82-84 84  dysfunction among south Indian women with metabolic syndrome. JCDR 2011 Apr, Vol-5(2): 152-154. 6. Uzunlulu M, Yorulmaz E, Oguz A. Prevalence of subclinical hypothyroidism in patients with metabolic syndrome. Endocrin J. 2007;54: 71-76. 7. Tkac I. Metabolic syndrome in relationship to type 2 diabetes and atherosclerosis. Diabetes Res Clin Pract. 2005;68 (suppl): S2-9. 8. Walsh JP, Brenner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med. 2005;165: 2467-72. 9. McDermott MT, Ridgway EC. Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Metab. 2001;86: 4585-90. 10. Duntas LH. Thyroid disease and lipids. Thyroid. 2002;12: 287-293.  11. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab. 2002;87(4): 1533-1538. 12. Luboshitzky R, Herer P. Cardiovascular risk factors in middle-aged women with subclinical hypothyroidism. Neuroendocrinology Letters. 2004;25(4): 262-266. 13. Kventy J, Heldgaard PE, Bladbejerg EM. Subclinical hypothyroidism is associated with low grade inflammation, increased triglyceride levels and predicts cardiovacular disease in males below 50 years. Clin Endocrinol. 2007;61: 232-238. 14. Sundaram V, Hanna AN, Koneru L, Newman HAI, Falko JM. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation. J Clin Endocrinol Metab. 1997;82: 3421-3424. 15. Asvold BO, Vatten LJ, Nilsen TI, Bjoro T. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur J Endocrinol. 2007;156(6): 707-712. 16. Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K. Subclinical hypothyroidism may be associated with high sensitive C-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J. 2005;52: 89-94. 17. Asvold BO, Bjoro T, Nilsen TI, Vatten VJ. Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population based study. J Clin Endocrinol Metab. 2007;92: 841-845. 18. Poonguzhali DV, Vinodhini VM, Ebenezer William, Kumar JS. Evaluation of Apolipoprotein-B levels in Dysglycemia. Asian J Pharm Clin Res. 2013; Vol6(3):112-114. 19. Dimitriadis G, Mitrou P, Lambadiari V. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab. 2006;91: 4930-4937.                     

PREVALENCE OF METABOLIC SYNDROME AND ITS COMPONENTS IN WOMEN WITH SUBCLINICAL HYPOTHYROIDISM

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PREVALENCE OF METABOLIC SYNDROME AND ITS COMPONENTS IN WOMEN WITH SUBCLINICAL HYPOTHYROIDISM

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