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A study of hs-CRP and lipid profile in hypothyroid adults at tertiary care hospital
Introduction
Thyroid dysfunction is one of the most prevalent endocrinopathies across the globe.[1] The prevalence of spontaneous hypothyroidism is 1-2% of all the thyroid disorders in the world.[2] In India thyroid disorders are the second most common glandular disorder of the endocrine system and are increasing predominantly among women.[3] Hypothyroidism is characterized by deficient thyroid hormone production which can be severe or moderate.[4] Common etiologies of hypothyroidism are dietary deficiency of iodi ne and Hashimotos thyroiditis, an auto-immune disease.[5],[6] Hypothyroidism is known for its effects on different organs system, leading to hypometabolism. Thyroid gland regulates a wide array of metabolic parameters of carbohydrate and lipid metabolism and has profound effects on the cardiovascular system.[7]
Severe deficit of thyroid hormones defines clinical hypothyroidism (CH) and is biochemically characterized by TSH concentration (usually >10 μIU/L) with low levels of free thyroxine (FT4) and or Free Triiodothyronine (FT3). The moderate form, called subclinical hypothyroidism (SCH) is defined biochemically as serum TSH concentration above the upper limit of reference range (> 4.5 - 10 μIU/L) with thyroid hormone levels that remain within the reference range.[8] CH has been found to be associated with atherogenic dyslipidemia by various researchers and is associated with higher risk of cardiovascular disease. It is known that CH is an established risk factor for atherosclerotic cardiac disease and associated with dyslipidemia and low-grade inflammation and hypercoagulability, but whether SCH is related to risk of CVD is controversial.[9]
The effect of serum thyroid hormones on lipid profile is a complex phenomenon. Thyroid hormoneshave various effects on both synthesis and degradation of lipids in vivo.[10] It acts predominantly through regulation of gene expression related to lipid metabolism.[11] Thyroid hormones through its nuclear receptors, induce HMG- Co enzyme A reductase, which is the first as well as the regulatory step in cholesterol biosynthesis, upregulates low density lipoprotein (LDL-c) receptors by gene activation and maintains serum TG by stimulation of tissue lipoproteinlipase enzyme. It also reduces the plasma HDL by increasing the activity of cholesteryl-ester transfer protein (CETP), hepatic lipase, expression of HDL receptors in the liver and helps reverse cholesterol transport through increased excretion of bile acids in the liver.[12]
Dyslipidemia is a common finding in patients with CH, consisting of high levels of total and LDL-c. Data regarding TG, HDL, Lp(a), apolipoprotein B, A1 components are scarce, reporting either higher or similar to euthyroid subjects levels.[13] The detected abnormalities in the lipid components are significantly improved after thyroxine replacement treatment. However, not all lipid parameters are corrected suggesting a more complex cause of dyslipidemi a in hypothyroidism.[14]
According to the Rotterdam study, a serum TSH level > 4.0 μU /l was found to be associated with a history of myocardial infarction and atherosclerosis of the abdominal aorta.[15] Contradictorily, the Whickham survey found no relationship between initial TSH levels and the development of ischemic heart disease over 20 years of follow up.[16]
Several signs and symptoms with hypothyroidism recommend an abnormality of inflammation. Thyroid hormones play an important role in cardiovascular hemodynamics, yet the association between elevated thyroid hormones and low-grade inflammation is still unknown.[17] The chronic inflammatory state lead to impaired endothelial dysfunction and vascular remodeling.
High sensitive c- reactive protein (hs -CRP) is a marker of chronic subclinical inflammation. Increased hs -CRP levels might be a key molecule linking inflammation to oxidative stress in atherosclerosis (Singh et al)[18] leading to CV risk.[19],[20] TSH induced synthesis of TNF-α by bone marrow cells might be the mechanism responsible for inflammatory process seen in hypothyroidism. The other significant finding is major role played by Cyclo-oxygenase-2 (COX 2) which is reported to enhance the production of autocoids that develop inflammation and as a consequence, endothelial dysfunction.[21]
Circulating concentrations of CRP fluctuate widely during acute responses to tissue damage or infection. It is a potential marker of more subtle and persistent systemic alterations that may be known as low grade inflammation.[22] Possible role of CRP in atherogenesis might be due to enhanced expression of local endothelial cell surface adhesion molecules, endothelin-1, reduced endothelial nitric oxide bioactivity. To explore the moderate elevations as in screening, performance of hs-CRP is recommended to better identify CRP variations.[23],[24]
In our study we hypothesized that hypothyroidism is associated with mild dyslipidemia associated with chronic inflammatory state as measured by hs-CRP. The basic aim is to study the same in the newly detected hypothyroid adults.
Objectives
To determine the thyroid profile, lipid parameters and high sensitive C- reactive protein in the study subjects
To compare the above parameters in hypothyroid patients (cases) and normal individuals (controls)
To compare the parameters in Clinical hypothyroidism (CH) and Subclinical hypothyroidism (SCH)
Materials and Methods
Study design: Hospital based Cross sectional study
Study setting: Department of Biochemistry in collaboration with General medicine, RRMCH, Bengaluru
Study population:
Group 1: Cases – 82 newly detected hypothyroid adults, age group: 18-55 years
Group 2: Controls – 82 normal healthy adults within same age group
Inclusion criteria
Cases: Newly detected hypothyroid cases between age group of 18-55 years attending General medicine OPD, RRMCH, Bengaluru
Controls: Age and sex matched healthy individuals
Exclusion criteria
Subjects who haven’t submitted written informed consent
Subjects having history of any Medical/ Surgical illness like Cardio vascular disorders, Diabetes Mellitus, kidney failure, Liver disorders and other major chronic illnesses
Hypothyroid adults with any other medications or treatments
Method of collection of data
Blood samples were collected with full aseptic precautions after obtaining informed consent. Clot activator that contains vacuum evacuated tubes for analysis of serum TSH, FT3, FT4, TC, HDL-c, LDL-c, TG, hs-CRP. Then after collection, serum samples were stored at -20º until analyzed. Anthropometric measurements for BMI, height (cm) and body weight (kg) were measured without shoes or cap.
Investigations done
Serum TSH, FT3 and FT4 by CLIA
Serum high sensitive C reactive protein by Immunoturbidimetric assay
Lipid parameters analyzed in Erba EM360 autoanalyzer, Serum TG: GPO Method, HDL and LDL cholesterol by precipitation method, Total cholesterol by cholesterol oxidase – peroxidase method.
Statistical analysis
Analysis was done using SPSS version-20 software. The mean and standard deviation for quantitative variables were calculated for the study.
Chi-square test, ANOVA test, students t test were applied whenever necessary. Pearson correlation coefficient was obtained to find out correlation between different parameters. p value < 0.05 was considered to be significant.
Result
As shown in [Table 1], both cases and controls were age matched. The mean age of cases and controls in our study was found to be 35 ± 11 years and 35 ± 10 years respectively (p = 0.76). Approximately 91% of cases and 79% of controls were females depicting a female preponderance ([Figure 1]). BMI values in the study were higher in cases (26.3 ± 4.8 kg/m2) compared to controls (24.8 ± 4.5 kg/m2) and was statistically significant (P = 0.04) ([Table 1])
In the study, the mean TSH levels (14.26 ± 8.9 μIU/ml) of cases were high compared to controls and was statistically significant (p < 0.001) ([Table 2]). The mean serum hs -CRP levels in both the study groups was within the reference range, but it was high and statistically significant in cases than in control (p = 0.005). The total cholesterol level in cases (181.79 ± 41.49 mg/dl) and control (183.22 ± 27.17 mg/dl) were within the reference range and there was no statistical significance (p = 0.79). Further it was found that HDL-c in cases (46.20 ± 8.97 mg/dl) and control (53.0 ± 6.3 mg/dl) were found to be lower in cases compared to controls and the difference was statistically significant (p < 0.001). The mean LDL-c value in cases (144.5 ± 33.9 mg/dl) and control (131.6 ± 31.4 mg/dl) was high in cases and the difference was statistically significant (p = 0.01). The triglyceride levels of cases (158.90 ± 51.64 mg/dl) were significantly higher than that of control (145.65 ± 28.35 mg/dl) and was statistically significant (p = 0.04).
As in [Table 3], hs -CRP levels were in within reference range for 78% of cases and 92.7% controls whereas above the normal range was seen in 22 % cases and only 7% controls.
([Table 4]) As per the Pearson’s correlation, there was a significant positive correlation between serum TSH and hs - CRP levels in cases (r = 0.27, p < 0.001).
To analyse the condition, Hypothyroid cases (n = 82) in our study was divided into two groups (subclinical hypothyroid and clinical hypothyroid) based on TSH and thyroid hormone levels. Out of 82, 65% (n = 53) were subclinical hypothyroid (SCH) and 35% (n =29) were clinical hypothyroid (CH) cases. A definite female preponderance was observed in the study.
In [Table 5], the mean age, BMI between the two groups did not differ significantly. There was a significant increase in serum TSH in CH (23.7 ± 8.7µIU/ml) as compared to SCH (9.0 ± 2.4 µIU/ml). The difference was statistically significant (p < 0.001). hs -CRP levels though high in CH than SCH were statistically insignificant (p = 0.64). Total cholesterol value was within the reference range in both the groups (CH and SCH) whereas TG was found to be high in CH compared to SCH and was found to be significant (p < 0.001).
There was no significant difference in HDL-c and LDL-c between the two groups (SCH & CH).
TSH and hs- CRP when compared between SCH, CH and controls showed a statistically significant difference between groups with p value <0.001. ([Table 6])
| Cases n=82 | Controls n=82 | P Value | |
| Age | 35.43±11.47 | 34.93±10.22 | 0.76 |
| BMI (Kg/m2) | 26.33 ± 4.89 | 24.87 ± 4.54 | = 0.04* |
| HypothyroidCases n=82 | Controls n=82 | P value | |
| T H µIU/ml | 14.26 ± 8.9 | 2.4 ± 0.96 | <0.001* |
| FT3 pg/ml | 1.9 ± 0.8 | 2.1± 0.8 | = 0.42 |
| FT4 ng/ml | 0.8 ± 0.4 | 0.8 ± 0.09 | = 1.00 |
| hs-CRP mg/l | 4.0 ± 2.8 | 2.8 ± 2.6 | = 0.005* |
| Total Cholesterol (mg/dl) | 181.79 ± 41.49 | 183.22±27.17 | = 0.79 |
| HDL-c (mg/dl) | 46.20±8.97 | 53.0±6.3 | < .001* |
| LDL-c(mg/dl) | 144.51±33.98 | 131.68±31.41 | = 0.01* |
| TG (mg/dl) | 158.90±51.64 | 145.65±28.35 | = 0.04* |
| Hypothyroid Cases =82 | Controls n=82 | ||
| hs-CRP mg/l | < 5 mg/l | 64 (78.0%) | 76 (92.7%) |
| ≥ 5 mg/l | 18 (22.0%) | 6 (7.3%) | |
| Total | 82 (100.0%) | 82 (100.0%) |
| Parameters | r value | P value |
| T H vs hs-CRP | 0.275** | <0.001 |
| Parameter | CH =29 | SCH n=53 | p value |
| Age (years) | 37.72 ± 12.02 | 34.17 ±11.07 | = .18 |
| BMI (kgm2) | 26.36 ± 3.97 | 26.30 ± 5.35 | = .16 |
| TSH (µIU/ml) | 23.7 ± 8.7 | 9.0 ± 2.4 | < .001* |
| FT3 (pg/ml) | 1.2 ± 0.7 | 2.3 ± 0.4 | < .001* |
| FT4 (ng/ml) | 0.5 ± .3 | 1.0 ± 0.2 | < .001* |
| hs-CRP (mg/l) | 4.2 ± 3.5 | 3.9 ± 2.3 | = .64 |
| TC (mg/dl) | 175.9 ± 31.1 | 188.8 ± 44.9 | = .15 |
| HDL-C (mg/dl) | 45.5 ± 9.4 | 46.5 ± 8.7 | = .61 |
| LDL-C (mg/dl) | 148.4 ± 37.0 | 142.3 ± 32.3 | = .43 |
| TG (mg/dl) | 208.2 ± 21.6 | 156.8 ± 52.9 | < .001* |
| Variales | CH (n=53) | CH (n=29) | Controls(=82) | Total | F value | P value |
| T H | 9.09±2.46 | 23.70±8.74 | 1.88± 0.96 | 8.07±8.86 | 326.52 | < .001 |
| hs- CRP | 3.96±2.35 | 4.23±3.56 | 2.07±2.6 | 3.06±2.92 | 10.63 | < .001 |
Discussion
Hypothyroidism is by far the most prevalent form of thyroid disorder and is more common in women.[25] It is characterized by a broad clinical spectrum ranging from an asymptomatic/subclinical condition to over the state of myxoedema, end organ effects and multi organ failure.[26] This study has investigated the possible association of hypothyroidism with hs-CRP, lipid profile both reportedly associated with risk of CVD.
A total of 164 subjects participated in this study. Out of the total. 82 subjects were newly detected hypothyroid subjects (cases) and 82 were healthy control. Both the cases and control were age matched. The mean age of cases and control was 35±11 years and 35±10 years respectively (p=0.76) ([Table 1]). Thyroid dysfunction is a common endocrine disorder with its prevalence increasing with age. About 91% of cases and 79% of control were females showing a female preponderance. Hypothyroidism is known to inflict females more than males ([Figure 1]). Devika Tayal et al (2012)[18] in their study observed a similar female predominance with a female to male ratio of 2.86 (females 5542 vs Males 1933)[18] A redox imbalance elicited by estrogen could be responsible for increased prevalence in female.[27],[28]
In this study BMI was higher in hypothyroid cases. Study conducted b y Nivedita Nanda et al (2012)[18], Kunal B.K[29] et al (2012)[18] reported similar observation with BMI in hypothyroidism. Thyroid hormones mediate their effects mainly through mechanism that stimulate basal metabolic rate, increase ATP expenditure, modulate adrenergic receptor number and responsiveness to catecholamines. Hypothyroid state characterized by slowing down of basal metabolic rate may be an important factor contributing to increase BMI in these cases.
The mean level of serum TSH was significantly higher in cases compared to control (14.26 ± 8.9 vs 2.4 ± 0.96 μIU/mL) respectively and was statistically significant (p<0.001). The mean serum FT3 levels (1.9 ± 0.8 vs 2.1 ± 0.8 pg/ml, p = 0.42) and serum FT4 levels (0.8 ± 0.4 vs 0.8 ± 0.09 ng/ml, p = 1.0) in both cases and control respectively were within the normal range ([Table 2]). Study done by Mohsin Shafi et al (2013)[18] on newly detected hypothyroid patients found that mean TSH levels higher in cases as compared to control (14.3 ± 10.1 μIU/L vs 1.8 ±0.7) and was statistically significant (p<0.01).[30] Thyroid hormone plays a crucial role in regulation of immune system and has the potential to dampen inflammatory cytokines such as INF-α, IL-6, IL-10. Several signs and symptoms suggest that hypothyroidism is an inflammatory state resulting from interaction of IL-6 on TNF and IL-1 leading to increase hs -CRP in this state. Recent studies found that moderate elevations of CRP correlate with future cardiovascular events justifying the use of this test to evaluate cardiovascular risk.[15]
This study showed that mean serum hs -CRP levels in both study groups were within reference range but the mean serum hs-CRP levels in cases was significantly higher (p=0.005) than in control. A significant positive correlation was also found between serum TSH and hs-CRP levels in cases (r = 0.27, p < 0.001) ([Table 4]).
Christ-crain et al (200 3) observed an elevation in CRP levels with progressive thyroid failure and a clear association between hypothyroidism and increased hs-CRP.[31] Tuzcu et al (2005)[18], Alpaslan T et al (2005)[15] in their stu dies of the association between coronary heart disease and SCH have reported that elevated hs -CRP levels suggest low grade inflammation predictive of CV risk in hypothyroid subjects.[15]
In contrary to this, a study conducted by Aksoy DY et al (2013)[18] on women could not validate a significant difference in hs-CRP levels between hypothyroid and control.[32]
The interaction of IL-6 on TNF-α and IL-1 results in the raised CRP levels in hypothyroidism. Lack of thyroid hormones may impair the rate of CRP clearance which may be one reason in increase in serum CRP level. Similarly, slow CRP uptake in target cells might also add to this phenomenon. The low grade inflammation which may be accountable for increased risk of developing CVD in hypothyroidism.[17]
Thyroid disorders are known to influence lipid metabolism and other CV risk factors predominantly. Dyslipidaemia is a well-recognized association of thyroid dysfunction which should be considered in the process of evaluating and treating dyslipidemic patients.[33],[34]
In this study, it was found that total cholesterol values had no statistical significance but HDL-c in cases was found to be lower compared to control and the difference was statistically significant (p < 0.001). The mean LDL-c and triglyceride in cases were higher than control with p = 0.001 and p = 0.04 respectively.
Sunanda et al (2012)[18] found that there was a strong positive association between TSH and lipid profile in hypothyroid patients and concluded that effect of hypothyroidism on the serum lipids is more pertinent in patients with higher TSH levels.[35] Khan Mah et al (2013)[18] also found a significant dyslipedemia i.e. significant increase in TC, LDL-c and TG levels and decrease in HDL-c levels.[36]
Slight elevation in TSH levels, preponderance of sub-clinical hypothyroid subjects and shorter duration of illness (newly detected cases) might be likelihood causes of mild dyslipidemia observed in the study.
In clinical hypothyroidism (CH), a decrease in LPL activity and the clearance of TG-rich lipoproteins[37] are found. Therefore CH patients may also present with elevated TG levels associated with increased levels of VLDL and occasionally fasting chylomicronemia[38] as observed with hypertriglyceridemia in hypothyroid cases in the study. Many previous studies concluded that CH patients have elevated atherogenic and oxidative stress markers. Hence, serum TSH measurement is the essential test for diagnosis of mild thyroid failure when the peripheral thyroid hormone levels are within normal reference range.[39]
In this study, a decreased HDL levels in cases was found. Clinical studies however reported a conflicting result about HDL-cholesterol plasma levels in hypothyroidism. The studies conducted by Caron et al found a reduction in HDL cholesterol and an increase in HDL after subsequent treatment with thyroxine. However, S. Valdemarssonet et al and E. Muls et al found an improvement in the mean HDL levels in the hypothyroidism with a reduction after treatment. Several proteins related with HDL metabolism are affected by thyroid hormones.[40],[41],[42]
The extent to which various levels of thyroid dysfunction affects CV event need to be debated.[23] Cappola et al in their study of Cardiovascular Health Study data found that there was no relationship between SCH or CH and prevalence of atherosclerotic disease, cardiovascular mortality o r all causes mortality.[43]
For better analysis in this study, hypothyroid cases were divided into subclinical hypothyroid (SCH) and clinical hypothyroid (CH). Majority of the target study group was female. The mean age, BMI values between two groups did not differ significantly. The CH subjects has higher serum TSH levels as compared to the subjects of SCH which was statistically significant (P<0.001). hs -CRP levels were found to be at risk level and was comparable in both CH and SCH but was statistically insignificant (p=0.64). Many studies have shown that high levels hs-CRP in women with SCH correlated with parameters of obesity which emphasizes the role of body weight in inflammation[44] and may consider as an additional risk factor for the development of atherosclerosis and CVD.[45],[46],[47]
Total cholesterol value was found to be within reference range in both the groups (CH and SCH) but TG value was found to be high in CH as compared to SCH which was found to be statistically significant (p<0.001). There was no significant differences in HDL-c, LDL-c between two groups. Cross sectional studies conducted by Jung CH et al (2003)[18] also reported that SCH is associated with increased levels of TC and LDL-c.
Thus subjects with CH in this study resulted in hypertriglyceridemia but in SCH subjects, other then the mild degree of TSH elevation and slight increase triglycerides, there was not any significant changes in the parameters studied.
The mean values of serum TSH and hs-CRP were higher in CH as compared to SCH and controls. It was observed that the difference was statistically significant (p<0.001).
Studies conducted by Biondi and Cooper have shown that SCH is associated with variable and inconsistent changes in above mentioned parameters in contradictory to CH in which significant changes are normally found.[48]
Two large population based studies-Whickham survey, National Health & Nutrition Examination Survey III (NHANES III) and other have highlighted the fact that serum TSH is the most powerful predictor of the outcome of SCH over a period of time. TSH values > 4 μIU/L and the presence of thyroid auto antibodies had very high chances of progression to overt hypothyroidism.[49],[50]
Hence, hypothyroid cases should be investigated for dyslipidemia and inflammatory markers since they help in prediction of CV risk. It is also essential to assess the progression to the clinical state and to finalize the course of treatment.
Limitations of the study
Small sample size and cross sectional study.
Conclusion
This study demonstrates that hypothyroidism is associated with dyslipidemia and low grade inflammation. Subclinical hypothyroidism was found to be more common than clinical hypothyroidism. Hypertriglyceridemia and at risk hs -CRP levels though seen in hypothyroid cases were more prominent in CH cases than SCH. The mild and inconsistent changes which were observed in the biochemical parameters in hypothyroidism (i.e. combination of both CH and SCH) may be due to the preponderance of subclinical hypothyroid cases in this study. However, dyslipidemia and inflammatory markers were found to be increased in the cases that helped in prediction and evaluation of patients at risk of cardiovascular disease.
Source of funding
None.
Conflict of interest
None.
References
- S Jha, N Ahmad. Prevelance of Thyroid Dysfunction in the patients visiting Tertiary Health care hospital, Faridabad; Haryana. Int J Sci Res 2013. [Google Scholar]
- M P J Vanderpump. The Epidemiology of thyroid disease. Br Med Bull 2011. [Google Scholar]
- N Kochupillai. Clinical endocrinology in India. Curr Sci 2000. [Google Scholar]
- P Lauberg, C Cerqueira, L Ovesen. Iodine intake as a determinant of thyroid disorders in populations. Clin Endocrinol Metab 2014. [Google Scholar]
- . . Health Organization/International Council for the Control of the Iodine Deficiency Disorders/United Nations Childrens Fund (WHO/ICCIDD/UNICEF). Assessment of the iodine deficiency disorders and monitoring their elimination. Geneva: World Health Organization 2007. [Google Scholar]
- A Saxena, P Kapoor, Saxena Shikha. Effect of levothyroxine therapy on dyslipidemia in hypothyroid patients. Internet J Med 2013. [Google Scholar]
- . Diabetes and Thyroid Disorders. Br J Diabetes Vasc Dis 2010. [Google Scholar]
- R J Garber, H R Cobin, Gharib Hossein. Clinical Practice Guidelines for Hypothyroidism In Adults: Cosponsored By The American Association Of Clinical Endocrinologists And The American Thyroid Association. Endocr Pract 2012. [Google Scholar]
- M Mahto, B Chakraborthy, H S Gowda. Are hsCRP Levels and LDL/HDL Ratio Better and Early Markers to Unmask Onset of Dyslipidemia and Inflammation in Asymptomatic Subclinical Hypothyroidism?. Ind J Clin Biochem 2012. [Google Scholar]
- Somasundaram Hariharan, Somanath Padhi, Sahoo Jayaprakash. Dyslipidemia in hypothyroid subjects with Hashimotos thyroiditis. Int J Med Sci Public Health 2015. [Google Scholar]
- Y Liu Yun, B Gregory. Thyroid Hormone Crosstalk with Nuclear Receptor Signaling in Metabolic Regulation. Trends Endocrinol Metab 2009. [Google Scholar]
- C V Rizos, M S Elisaf, E N Liberopoulos. Effects of Thyroid Dysfunction on Lipid Profile. Cardiovasc Med J 2011. [Google Scholar]
- Wang Chaoxun. The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases. J Diabetes Res 2013. [Google Scholar]
- Peppa Melpomeni, Betsi Grigoria, Dimitriadis George. Lipid Abnormalities And Cardiometabolic Risk In Patients With Overt And Subclinical Thyroid Disease. J Lipids 2011. [Google Scholar]
- Alpaslan Tuzcu, Mihat Bahceci, Deniz Gokalp. Subclinical Hupothyroidism May Be Associated With Elevated High Sensitive C Reactive Protein (Low Grade Inflammation) And Fasting Hyperinsulinemia. 2005. [Google Scholar]
- Brenta Gabriela, Mario Vaisman Jose, Augusto Sgarbi. Clinical practice guidelines for the management of hypothyroidism. Endocrinol Metab 2013. [Google Scholar]
- Plmieri Serafino, Lombardi Emiliano, - Gaetano. Effects of Thyroid Hormone on the Cardiovascular System. J Clin Endocrinol Metab 2004. [Google Scholar]
- S Singh, P Sarkar Dey. Serum lipids, tHcy, hs-CRP, MDA and PON-1 levels in SCH and overt hypothyroidism: effect of treatment. Acta Bomed 2014. [Google Scholar]
- I Kushner, A R Sehgal. Is high-sensitivity C-reactive protein an effective screening test for cardiovascular risk?. Arch Intern Med 2002. [Google Scholar]
- S Taddei, N Ceraccio. Low grade systemic inflammation causes endothelial dysfunction in patients with Hashimotos Thyroiditis. J Clin Endocrinol Metab 2006. [Google Scholar]
- Singh Bhawna, Saxena Alpana. Surrogate markers of insulin resistance. World J Diabetes 2010. [Google Scholar]
- H Mehdi Shishehbor, Bhatt Deepak L, J Eric. Using C-reactive protein to assess cardiovascular disease risk. Leveland Clin J Med 2009. [Google Scholar]
- Yousuf Omair, D Bibhu Mohanty, S Seth Martin. High-Sensitivity C-Reactive Protein and Cardiovascular Disease. J Am Cardiol 2013. [Google Scholar]
- J A Dhok, S P Adole, V P Puppalwar. Status of Thyroid disorders at Acharya Vinobha Bhave Rural Hospital, Sawangi (Meghe), Wardha, India. Thyroid Res Pract 2015. [Google Scholar]
- A Unnikrishnan Gopalakrishnan, S Kalra, K Sahay. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian Journal Endocrinol Metab 2013. [Google Scholar]
- D Tayal, R Chawla, S Arora. Dynamic Changes in Biochemical Markers of Renal Function with Thyroid Status - A Study in Indian Population. Internet J Med 2009. [Google Scholar]
- R S Fortunato, A C Ferreira, F Hecht. Sexual dimorphism and thyroid dysfunction: a matter of oxidative stress?. J Endocrinol 2014. [Google Scholar]
- Nanda Nivedita, Bobby Zachariah, Abdul Hamide. Insulin Resistance Among Hypothyroid Patients In India. Asian J Biochem 2012. [Google Scholar]
- Shafi Mohsin, Waqar Azim, M. Asif Nawaz. Effect of Hypothyroidism On Lipid Profile In Asymptomatic Newly Diagnosed Patients. Biomedica 2013. [Google Scholar]
- Christ-Crain. Elevated C-reactive protein and homocysteine values: Cardiovascular risk factors in hypothyroidism? A cross-sectional and double-blind, placebo-controlled trial. Atheroscler 2002. [Google Scholar]
- Aksoy Yazgan Dugyu, Nese Cinar, Harmanci Alya. Serum Resistin and High Sensitive CRP Levels in Patients with Subclinical Hypothyroidism Before and after L-Thyroxine Therapy. 2013. [Google Scholar]
- . Upadhayay Kant R. Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders. Journal of Lipids 2015. [Google Scholar]
- . Abd lazeem Siddeg. Evaluation of serum lipid profile in Sudanese patient with thyroid Dysfunction. J Applied Med Sci 2015. [Google Scholar]
- . Aml Mohamed Nada. Effect of treatment of overt hypothyroidism on insulin resistance. World J Diabetes 2013. [Google Scholar]
- Khan MAH, Majumder Ishaque, M Hoque, M Fariduddin, F H Mollah, M I Arslan. Lipid Profile in Hypothyroid Patients: A Cross Sectional Study. Bangladesh J 2013. [Google Scholar]
- W Y Lee, J Y Suh, E J Rhee, J S Park, K C Sung, S W Kim. Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lp(a) levels according to thyroid function status. Arch Med Res 2004. [Google Scholar]
- A A Al-Tonsi, A A Abdel - Gayoum, M Saad. The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders. Exp Mol Pathol 2004. [Google Scholar]
- Fatourechi Vehab. Subclinical Hypothyroidism: An Update For Primary Care Physicians. Mayo Clinic Proceedings 2009. [Google Scholar]
- X Feng, Y Jiang, P Meltzer. Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA microarray. Molec Endocrinol 2000. [Google Scholar]
- Martha Franco. Pleiotropic Effects of thyroid Hormones: Learning from Hypothyroidism. J Thyroid Res 2011. [Google Scholar]
- L H Duntas. Thyroid Disease and lipids. Thyroid 2002. [Google Scholar]
- A R Cappola, P W Landenson. Hypothyroidism And Atherosclerosis. J Clin Endocrinol Metab 2003. [Google Scholar]
- David A Marrow, Paul M Ridke. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circ 1999. [Google Scholar]
- E A Nikkila, M Kekki. Plasma triglyceride metabolism in thyroiddisease. J Clin Invest 1972. [Google Scholar]
- . . Tsugikazu Komoda.Textbook of The HDL Handbook: Biological Functions and Clinical Implications 2013. [Google Scholar]
- L Kebapcilar, B Akinci, F Bayraktar. Subclinical hypothyroidism could be regarded as benign condition in oxidative stress but not in atherosclerosis. Endocrine 2001. [Google Scholar]
- Bernadette Biondi, Cooper S David, -. The Clinical Significance of Subclinical Thyroid Dysfunction. Endocr Rev 2008. [Google Scholar]
- J J Diez, P Iglesias. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab 2004. [Google Scholar]
- J Gussekloo, E Van Exel, A J De Craen, A E Meinders. Thyroid status, disability and cognitive function, and survival in old age. J Am Med Assoc 2004. [Google Scholar]