|Year : 2013 | Volume
| Issue : 2 | Page : 60-64
Prevalence of hypothyroidism in patients with metabolic syndrome
Lalit K Meher1, Suryanath Kalapurakal Raveendranathan1, Sunil K Kota2, Jagannath Sarangi1, Siba N Jali1
1 Department of Medicine, MKCG Medical College, Berhampur, Orissa, India
2 Department of Endocrinology, Medwin Hospital, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||16-Apr-2013|
Sunil K Kota
Department of Endocrinology, Medwin Hospital, Chiragh Ali Lane, Nampally, Hyderabad, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Aim: Hypothyroidism and metabolic syndrome are well-associated risk factors for atherogenic cardiovascular disease. Insulin resistance, being a common pathogenic mechanism in both, can cause a considerable overlap between hypothyroid and metabolic syndrome population. This cross-sectional study was intended to assess the thyroid function in patients with metabolic syndrome and to investigate the association between hypothyroidism and metabolic syndrome. Materials and Methods: One hundred patients with metabolic syndrome as per National Cholesterol Education Program-Adult Treatment Panel (NCEP ATP) III criteria and 50 controls (0 out of 5 criteria) attending the internal medicine outpatient clinic were included in the study. Patients were subjected to anthropometry, evaluation of vital parameters, and lipid and thyroid profile, along with other routine laboratory parameters. Students' "t" test, Chi-square test, linear regression, and multiple logistic regression models were used for statistical analysis. P value <0.05 was considered significant. Results: Body mass index, waist circumference, mean systolic pressure, diastolic pressure, fasting blood sugar, total cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and thyroid stimulating hormone (TSH) were significantly higher, and free triiodothyronine (FT3), free thyroxine (FT4), and high density lipoprotein (HDL) cholesterol were significantly lower in the study group compared to the control group. In the metabolic syndrome group, 22 had subclinical hypothyroidism (22%), 4 were overtly hypothyroid (4%), and 74 were euthyroid (74%). Subclinical hypothyroidism was significantly associated with metabolic syndrome group (P = 0.032). There was significant linear association between TSH levels and total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol across the metabolic syndrome group in the linear regression model. Multiple logistic regression analysis recognized the association between body mass index with subclinical hypothyroidism (P = 0.006) in the metabolic syndrome group. Conclusion: It is concluded from this study that there is significant association between subclinical hypothyroidism and metabolic syndrome, and it highlights the importance of thyroid function tests in patients with metabolic syndrome.
Keywords: Body mass index, hypothyroidism, metabolic syndrome, obesity
|How to cite this article:|
Meher LK, Raveendranathan SK, Kota SK, Sarangi J, Jali SN. Prevalence of hypothyroidism in patients with metabolic syndrome. Thyroid Res Pract 2013;10:60-4
|How to cite this URL:|
Meher LK, Raveendranathan SK, Kota SK, Sarangi J, Jali SN. Prevalence of hypothyroidism in patients with metabolic syndrome. Thyroid Res Pract [serial online] 2013 [cited 2019 Aug 19];10:60-4. Available from: http://www.thetrp.net/text.asp?2013/10/2/60/110583
| Introduction|| |
Metabolic syndrome (MetS) and hypothyroidism are well-established forerunners of atherogenic cardiovascular disease. MetS includes a cluster of risk factors characterized by hypertension, dyslipidemia, hyperglycemia, and prothrombotic and proinflammatory conditions which accelerate the atherogenic process in the body. , Hypothyroidism is well known to cause hyperlipidemia, diastolic hypertension, endothelial dysfunction, and cardiovascular disease. , Considerable overlap occurs in the pathogenic mechanisms of atherosclerotic cardiovascular disease by MetS and hypothyroidism. Insulin resistance has been studied as the basic pathogenic mechanism in MetS. , Role of insulin resistance in development of dyslipidemia in hypothyroidism has been suggested in recent studies.  This relationship with insulin resistance can lead to a considerable overlap between the population subsets of MetS and hypothyroidism as well. A study on thyroid dysfunction in MetS population may help us to know the magnitude of overlap of these two groups and may highlight the importance of thyroid function tests in identifying hypothyroid population from MetS. This can lead to proper planning and adequate management strategies, resulting in significant reduction in cardiovascular morbidity and mortality due to MetS by effective thyroid replacement therapy. This study intended to assess thyroid function in patients with MetS and to investigate the association between hypothyroidism and MetS.
| Materials and Methods|| |
This cross-sectional study was conducted in outpatient department of MKCG Medical College, Berhampur in southern Orissa. One hundred patients with MetS who fulfilled the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) III criteria [three out of five criteria positive, namely, blood pressure ≥130/85 mm Hg or on antihypertensive medications, fasting plasma glucose >100 mg/dl or on anti-diabetic medications, fasting triglycerides >150 mg/dl, high density lipoprotein cholesterol (HDL-C) <40 mg/dl in males and <50 mg/dl in females, waist circumference >102 cm in men and 88 cm in women] were included in the study group.  Fifty patients who had no features of MetS (0 out of 5 criteria for MetS) were included in the control group. The study protocol was approved by institutional ethics committee and informed consents were obtained from the study participants, after they were duly explained about the protocol. The study was carried out over a period of 2 years.
Patients with liver disorders, renal disorders, congestive cardiac failure; pregnant women; patients on oral contraceptive pills, statins, and other medications that alter thyroid functions and lipid levels; and those who were under treatment for any thyroid-related disorder were excluded from the study. Acutely ill patients were excluded taking into account sick euthyroid syndrome. Blood pressure was measured over the right arm with the patient lying supine. Three readings were taken and a mean value of the readings was taken as the final recording. Waist circumference was measured at the plane between anterior superior iliac spines and lower costal margin at the narrowest part of the waistline while the patient was standing and during expiration.
Fasting blood samples were obtained (venous blood samples taken after overnight fast of a minimum of 8 h); glucose, total cholesterol, low density lipoprotein cholesterol (LDL-C), HDL-C, and triglyceride levels were determined. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) measurements were made using electrochemiluminescence immunoassay (ECLIA method). Normal range for TSH was 0.27-4.2 μIU/ml, FT3 was 1.4-4.2 pg/ml, and for FT4 was 0.93-1.7 ng/dl. A high serum TSH level (4.2-10 μIU/ml) and normal FT3 and FT4 levels were required for the diagnosis of subclinical hypothyroidism. Patients with high TSH (>10 μIU/ml) and low FT3 and FT4 levels were classified as being overt hypothyroid. Patients with normal TSH, FT3, and FT4 were considered euthyroid. Body mass index (BMI) was calculated by dividing weight in kilograms by height in meters squared.
Baseline characteristics of the study participants were expressed in mean ± SD and percentage. Student's "t " test was used to analyze differences in baseline characteristics between the study group and the control group. Linear regression model was created to know any significant relationship between the components of MetS and TSH levels. Chi-square test was used to analyze the association between MetS and hypothyroidism. Associations between patient characteristics (age, gender, mean systolic blood pressure, mean diastolic blood pressure, waist circumference, total cholesterol, HDL-C, LDL-C, triglycerides, fasting blood sugar) and subclinical hypothyroidism in the study group were analyzed using multiple logistic regression. P value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS windows version 17.0 software (SPSS Inc., Chicago, IL, USA).
| Results|| |
Of the 100 patients in the study group, 55 were females (55%) and 45 were males (45%). Of the 50 persons in the control group, 26 (52%) were females and 24 (48%) were males. The baseline characteristics of the two groups are depicted in [Table 1]. The two groups were similar with respect to age and sex distribution. Eighteen patients in the study group had goiter with mean TSH of 7.34 ± 4.37 μIU/ml, which was higher than the rest of the patients with no goiter (4.42 ± 3.43 μIU/ml, P = 0.03). However, BMI, waist circumference, mean systolic pressure, diastolic pressure, fasting blood sugar, total cholesterol, LDL-C, triglycerides, and TSH were significantly higher in the study group compared to the control group. HDL-C was significantly lower in the study group [Table 1].
In linear regression model, showing the correlation between the components of MetS with levels of TSH [Table 2], TSH had significant positive linear association with triglycerides, total cholesterol, and LDL-C, and significant negative linear association with HDL-C. Distribution of thyroid dysfunction across the group was analyzed in the study. In the MetS group, 4 (4%) of the cases had overt hypothyroidism, 22 (22%) had subclinical hypothyroidism, and 74 (74%) were euthyroid. In the control group, 1 (2%) had overt hypothyroidism, 4 (8%) had subclinical hypothyroidism, and the rest 45 (90%) were euthyroid. Subclinical hypothyroidism had significant association with MetS when assessed by Chi-square test, with P = 0.03.
|Table 2: Correlation between components of metabolic syndrome and levels of TSH across the metabolic syndrome group (linear regression model)|
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Association between subclinical hypothyroidism and components of MetS was analyzed using logistic regression analysis [Table 3]. Subclinical hypothyroidism showed significant association with BMI when analyzed using logistic regression models in the MetS case group (P = 0.006, CI 0.412-0.859).
|Table 3: Association between patient characteristics and subclinical hypothyroidism in the metabolic syndrome group (logistic regression analysis)|
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| Discussion|| |
This cross-sectional study was conducted in outpatient department of Medicine, MKCG Medical College, Berhampur, which is a representative of the general population at large in usual clinical practice. The MetS group included 100 cases with 45 males and 55 females, while the control group included 50 cases with 24 males and 26 females.
The two groups were similar in their distribution of age (P = 0.408) and gender. In this study, the mean systolic pressure, diastolic pressure, fasting blood sugar, total cholesterol, LDL-C, triglycerides, waist circumference, and BMI were significantly higher and HDL-C levels were significantly lower in the MetS group than in the control group. These findings were similar to those obtained in the studies on Hispanic population by Garcia et al, and on Chennai urban population by Shantha et al. ,
Thyroid function in both the MetS group and control group were assessed with FT3, FT4, and TSH assay [Table 1]. FT3 was significantly lower in the MetS group (P = 0.003) than in the control group. TSH was significantly higher in the MetS group than in the control group (P = 0.001). FT4 was lower in the control group with a P value of 0.217.
A linear regression model was created to assess the association between the components of MetS and level of TSH [Table 2]. TSH had significant positive linear association with total cholesterol, LDL-C, and triglyceride, and significant negative linear association with HDL-C in the linear regression model. The Nord-Trondelag health (HUNT) study concluded that within the range of TSH that is considered clinically normal, increasing level of TSH is associated with less favorable lipid concentrations. The association with serum lipids was linear across the entire reference range of TSH.  Although our study covered groups with both normal and higher TSH (unlike the HUNT study which included only euthyroid individuals), there was a linear relation between lipid concentration and TSH levels across the entire range of TSH, which supports the role of thyroid hormones in the regulation of lipid metabolism, a dysregulation of which leads to MetS. A similar study done in MetS group in the Hispanic population has shown linear association of TSH with total cholesterol, LDL-C, triglycerides, and waist circumference, but no association with HDL-C. 
The relation between hypothyroidism and cardiovascular disease is not well proven. In a study including 2730 men and women, aged 70-79 years, subclinical hypothyroidism was associated with an increased risk of congestive heart failure among older adults with a TSH level of 7.0 mIU/l or greater, but not with other cardiovascular events and mortality.  Another study found that there was no relationship between baseline TSH and cardiovascular mortality. 
The prevalence of thyroid dysfunction was analyzed in our study. Our study showed a high prevalence of subclinical hypothyroidism (22%) and overt hypothyroidism (4%) in the MetS group. In the control group, only 8% had subclinical hypothyroidism and 2% had overt hypothyroidism. In a recent population-based study in adult population in India, the prevalence of hypothyroidism was 3.9% while that of subclinical hypothyroidism was 9.4%.  According to the report by Shantha et al., the prevalence of overt hypothyroidism was 7.4% and that of subclinical hypothyroidism was 21.9% in the MetS population. 
Our study showed a significant association of subclinical hypothyroidism with MetS (P = 0.03). This study supports the results of Shantha et al.'s study, which showed the association of MetS and primary hypothyroidism in the urban population.  The study by Uzunzulu et al, also had shown significant association of subclinical hypothyroidism and MetS, which supports our data. 
Association of subclinical hypothyroidism with components of MetS was assessed by multiple logistic regression analysis in the present study. BMI showed significant association with subclinical hypothyroidism in persons with MetS (P = 0.006), whereas there was no statistically significant association with total cholesterol, triglycerides, LDL-C and HDL-C. According to our present study, MetS patients with higher BMI are more prone for having associated subclinical hypothyroidism. Knudsen et al.'s study has shown that even small differences in thyroid function are associated with changes in BMI. The possible underlying mechanisms for this relation are still not clear and remain to be explained.  However Kota et al, have recently demonstrated absence of any significant relation between severity of obesity and serum TSH level.  In a cross-sectional study including 1333 euthyroid participants, subjects with a TSH in the upper normal range (2.5-4.5 mU/l) were more obese, had higher triglycerides, and had an increased likeliness for the MetS. Therefore, a TSH below 2.5 mU/l was proposed to be associated with a favorable metabolic profile.  Another study including 3148 subjects concluded that subclinical hypothyroidism was not associated with an increased risk for MetS. Despite this, low thyroid function (even in the euthyroid state) predisposed to higher cholesterol, glucose, insulin, and insulin resistance.  Perhaps TSH elevation stimulates the secretion of inflammatory cytokines, which leads to an increase in the components of MetS.  Literature on the effect of treatment of subclinical hypothyroidism on components of MetS is scarce. As such, it was suggested that whether lowering TSH to levels below 2.5 mU/l improves metabolism needs to be investigated in intervention trials. 
Though there have been enough reports earlier on insulin resistance in hyperthyroidism, studies by Rochon et al and Stanicka et al, have demonstrated that hypothyroidism can also lead to insulin resistance. , Subclinical hypothyroidism has also been demonstrated to cause insulin resistance in a few studies. , This relationship with insulin resistance can partly explain the increased incidence of hypothyroidism in patients with MetS, which refers to one such condition where insulin resistance plays a central role in the clustering of risk factors for cardiovascular disease.
| Conclusion|| |
There is significant association between subclinical hypothyroidism and MetS. It is advisable to assess the thyroid function in all patients with MetS because unless hypothyroidism is excluded, a large number of patients with thyroid dysfunction will be mislabeled as MetS, which will influence the management of these cases.
| References|| |
|1.||Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415-28. |
|2.||Grundy SM. Metabolic syndrome: Connecting and reconciling cardiovascular anddiabetes worlds. J Am Coll Cardiol 2006;47:1093-100. |
|3.||Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam Study. Ann Intern Med 2000;132:270-8. |
|4.||Fernández-Real JM, López-Bermejo A, Castro A, Casamitjana R, Ricart W. Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent vasodilation in healthy euthyroid subjects. J Clin Endocrinol Metab 2006;91:3337-43. |
|5.||Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. |
|6.||DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14:173-94. |
|7.||Singh BM, Goswami B, Mallika V. Association between insulin resistance and hypothyroidism in females attending a tertiary care hospital. Indian J Clin Biochem 2010;25:141-5. |
|8.||Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97. |
|9.||Garduño-Garcia J de J, Alvirde-Garcia U, López-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, et al. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol 2010;163:273-8. |
|10.||Shantha GP, Kumar AA, Jeyachandran V, Rajamanickam D, Rajkumar K, Salim S, et al. Association between primary hypothyroidism and metabolic syndrome and the role of C reactive protein: A cross-sectional study from South India. Thyroid Res 2009;2:2. |
|11.||Asvold BO, Vatten LJ, Nilsen TI, Bjøro 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;156:181-6. |
|12.||Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005;165:2460-6. |
|13.||Sathyapalan T, Manuchehri AM, Rigby AS, Atkin SL. Subclinical hypothyroidism is associated with reduced all-cause mortality in patients with type 2 diabetes. Diabetes Care 2010;33:e37. |
|14.||Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Indian J Endocrinol Metab 2011;15(Suppl 2):S78-81. |
|15.||Uzunlulu M, Yorulmaz E, Oguz A. Prevalance of subclinical hypothyroidism in patients with metabolic syndrome. Endocr J 2007;54:71-6. |
|16.||Knudsen N, Laurberg P, Rasmussen LB, Bülow I, Perrild H, Ovesen L, et al. Small differences in thyroid function may be important for body mass index and occurrence of obesity in the population. J Clin Endocrinol Metab 2005;90:4019-24. |
|17.||Kota SK, Meher LK, Jammula S, Kota SK, Rao ES, Modi KD. Obesity and thyrotropinemia: Association in Indian adults. Thyroid Res Pract. 2013;10:4-7. |
|18.||Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, et al. A high normal TSH is associated with the metabolic syndrome. Clin Endocrinol (Oxf) 2010;72:696-701. |
|19.||Lai Y, Wang J, Jiang F, Wang B, Chen Y, Li M, et al. The relationship between serum thyrotropin and components of metabolic syndrome. Endocr J 2011;58:23-30. |
|20.||Rochon C, Tauveron I, Dejax C, Benoit P, Capitan P, Fabricio A, et al. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci (Lond) 2003;104:7-15. |
|21.||Stanická S, Vondra K, Pelikánová T, Vlcek P, Hill M, Zamrazil V. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy. Clin Chem Lab Med 2005;43:715-20. |
|22.||Maratou E, Hadjidakis DJ, Peppa M, Alevizaki M, Tsegka K, Lambadiari V, et al. Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism. Eur J Endocrinol 2010;163:625-30. |
|23.||Dessein PH, Joffe BI, Stanwix AE. Subclinical hypothyroidism is associated with insulin resistance in rheumatoid arthritis. Thyroid 2010;14:443-6. |
[Table 1], [Table 2], [Table 3]
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