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 Table of Contents  
Year : 2018  |  Volume : 13  |  Issue : 4  |  Page : 195-198

Association between C-reactive protein and interleukin-6 levels in subclinical hypothyroid patients

Department of Biochemistry, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India

Date of Web Publication16-Apr-2019

Correspondence Address:
Dr. Madhur Gupta
Department of Biochemistry, NKP Salve Institute of Medical Sciences and Research Centre, Digdoh Hill, Hingna Road, Nagpur - 440 019, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jdmimsu.jdmimsu_6_18

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Background: The relationship between subclinical hypothyroidism (SCH) and cardiovascular disease has been one of the most popular topics recently. Our study aims to investigate the presence of the well-known preceding clinical situations of atherosclerosis such as endothelial dysfunction and inflammation in SCH.
Materials and Methods: The study population comprised 50 patients with recently diagnosed SCH and 50 healthy controls. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were estimated by enzyme-linked fluorescent immunoassay for the diagnosis of SCH. Total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDLC) were estimated by kit method in Siemens machine. Low-density lipoprotein cholesterol (LDLC) and very LDLC were calculated using Friedewald formula. Inflammatory marker C-reactive protein was estimated by kit method in Siemens and IL-6 by enzyme-linked immunosorbent assay.
Results: In this study, the level of TSH ± standard deviation (8.56 ± 1.26 vs. 0.63 ± 0.16) was significantly higher (<0.001) in SCH patients, whereas FT3and FT4levels were within the normal range. TC, triglycerides, and LDLC were significantly higher in patients group, while the HDLC was significantly lower in SCH patients compared to euthyroid group. TSH level was positively correlated with inflammatory markers in SCH.
Conclusion: This study suggests that SCH patients have increased inflammatory markers along with dyslipidemia due to that the future risk of further development of cardiovascular disorder can occur. Level of inflammatory makers increases in patients as disease progresses if left untreated.

Keywords: C-reactive protein, interleukin-6, subclinical hypothyroidism

How to cite this article:
Uppu SD, Gupta M. Association between C-reactive protein and interleukin-6 levels in subclinical hypothyroid patients. J Datta Meghe Inst Med Sci Univ 2018;13:195-8

How to cite this URL:
Uppu SD, Gupta M. Association between C-reactive protein and interleukin-6 levels in subclinical hypothyroid patients. J Datta Meghe Inst Med Sci Univ [serial online] 2018 [cited 2020 May 25];13:195-8. Available from: http://www.journaldmims.com/text.asp?2018/13/4/195/256213

  Introduction Top

Subclinical hypothyroidism (SCH) is a common endocrine disorder, which affects worldwide population.[1] According to an Indian Epidemiological study, the prevalence of SCH is 8.73% in females and 7.17% in males.[2] SCH is defined as a serum thyroid-stimulating hormone (TSH) concentration above the statistically defined upper limit of the reference range when serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations are within their reference ranges. These thyroid function tests were documented for 6 months.[3]

Overt hypothyroidism is defined as a combination of high TSH with low (FT4). Patients of SCH are mostly asymptomatic or have minimal symptoms. Thus, SCH is solely a laboratory diagnosis.[4]

Thyroid disease is associated with various metabolic abnormalities, due to the effect of thyroid hormones on nearly all major metabolic pathways. Thyroid hormones regulate the basal energy expenditure through their effect on protein, carbohydrate, and lipid metabolism. Dyslipidemia is a common metabolic abnormality in patients with thyroid disease, either in the overt or subclinical forms of the disease and constitutes the end result of the effect of thyroid hormone in all aspects of lipid metabolism leading to various quantitative and/or qualitative changes of triglycerides, phospholipids, cholesterol, and other lipoproteins.[5]

Due to the presence of altered lipid profile, patients may also have further development of cardiac disease. Atherosclerosis is an inflammatory disorder, associated with accumulated cholesterol concentration might be developed in the future in SCH.[6] Some of the inflammatory markers are quite effective and well-known future predictors of cardiovascular risk.[7]

C-reactive protein (CRP) is an effective tool for the diagnosis of cardiac risk.[8] Activity of CRP is induced by a specific cytokine, interleukin-6 (IL-6), and important and well-established markers for assessment of inflammation.[9] Studies in the past have created confusion with respect to such inflammatory markers in SCH from no risk to definite risk.[10],[11]

Therefore, the aim of this study was to investigate the relationship between SCH and inflammatory markers (CRP and IL-6).

  Materials and Methods Top

A case–control study was conducted in the Department of Biochemistry at our Institute. The study group included 50 newly diagnosed cases of SCH aged above 35 years and 50 euthyroid controls. This study was approved by the Institutional Ethics Committee. All the participants gave informed consent before undergoing further investigations.

Inclusion criteria

SCH cases having TSH in the range of 4.50–10.00 mIU/L, FT3, and FT4 within normal limits and the euthyroid controls having normal TSH (0.3–4.5 mIU/L) were included in the study.

Exclusion criteria

Known hypothyroidism cases, thyroidectomy cases; patients with external radiation, previous radioactive iodine therapy, consumption of drugs known to cause SCH, patients with diabetes mellitus, other systemic illness, renal and hepatic failure cases, and patients on statins were excluded from the study.

The participants were selected from the cases referred to our clinical biochemistry laboratory by other departments (medicine, surgery, and gynec) requesting for thyroid profile, suspecting different thyroid disorders. We performed thyroid profile on such cases and included only those participants that come under the category of SCH.

As SCH is purely a laboratory diagnosis, we further requested these patients for lipid profile and inflammatory markers explaining them to the aim of our study.

Venous blood samples were drawn at 8.00 am following a 12 h fast in a plain bulb from the participants with all aseptic precautions. Blood samples were centrifuged within 30 min. At 3000 rpm for 5 min, serum was separated. Serum TSH, FT3, and FT4 were estimated by enzyme-linked fluorescence assay method on Vidas Automated Immunoassay Analyzer.

Estimation of serum cholesterol was done by cholesterol oxidase, peroxidase method, triglycerides by enzymatic end-point method, and high-density lipoprotein cholesterol (HDLC) done by direct measure on Siemens dimensions. LDL and VLDL were done by calculated method using Friedewald format.

CRP was measured by particle-enhanced turbidimetric immunoassay (PEITA) technique on Siemens. The statistical analysis was done by Student's t-test and simple correlation of SCH patient's data of TSH with other parameters.

  Observations and Results Top

It can be deduced from [Table 1] that the mean values of serum TSH are significantly higher in SCH patients (TSH 8.56 ± 1.26) compared to that of control participants (TSH 0.63 ± 0.18). Levels of serum FT3 and FT4 were within the normal reference range and did not show a significant difference [Table 1]. Whereas, the mean values of total cholesterol (TC), triglycerides, VLDL, and LDL/high-density lipoprotein (HDL) ratio were increased in SCH patients (TC 248.4 ± 25.83, triglycerides 217.78 ± 83.82, VLDL 43.15 ± 11.07, LDL 163.63 ± 21.29, and LDL/HDL 3.97 + 0.76) as compared to control group (TC 136.34 ± 11.44, triglycerides 85.8 ± 9.96, VLDL 17.16 ± 1.99, LDL 72.16 ± 10.90, and LDL/HDL 1.49 ± 0.24). Similarly, CRP and IL-6 values were also increased in SCH patients (CRP 12.7 ± 2.34, IC 6–60.24 ± 5.68), when compared to control group (CRP 1.7 ± 0.76, IL-6 11.37 ± 3.04).
Table 1: Levels of thyroid-stimulating hormone, lipid profile, and inflammatory markers in subclinical hypothyroidism patients vis-a-vis control

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It can be deduced from [Table 2] that the correlation of TSH with TC, triglycerides, VLDL, LDL, and LDH/HDL ratio was significantly positive in SCH patients. Similarly, the correlation of TSH with CRP and IL-6 was also significantly positive. Whereas, the correlation of TSH with FT3 was negative and with FT4 and HDL was positive in SCH but not statistically significant.
Table 2: Correlation of thyroid-stimulating hormone with lipid profile and inflammatory markers in subclinical hypothyroidism patient's

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  Discussion Top

SCH is more common than overt hypothyroidism. In recent times, it is being diagnosed more frequently than overt hypothyroidism.[12] The continuing debatable aspects regarding SCH are the associated dyslipidemic state, cardiovascular risk, and neuromuscular and psychiatric dysfunction underlying pro-inflammatory state, etc. The clear concepts in this aspect are yet to be obtained.[13],[14]

This study supports the hypothesis that SCH is associated with relatively increased inflammatory markers levels along with dyslipidemia compared to control group and they can give rise to the future development of cardiovascular risk in SCH. The levels of inflammatory markers were found to be elevated in patients group as compared to control in this study.

CRP is a very well-established, strong predictor of cardiovascular events.[15] In this study, both case and control groups did not have any medical history of inflammatory disease.

Several studies done in the past have produced varied results regarding the SCH and disturbed lipid parameters, which are still not clearly defined.[16],[17]

In our study, TSH is positively correlated with values of all the lipid parameters estimated in SCH patients except HDLC. Increased levels of TC, triglycerides, and LDL cholesterol in SCH in this study were also observed by various studies.[18],[19] HDL cholesterol concentration is decreased in our study; the same results are also observed in Erdem et al.[20]

SCH was not associated with hyperlipidemia in the Whickham survey.[15] In the Rotterdam study, TC was lower in SCH patients as compared to euthyroid patients.[21]

The occurrence of cardiovascular event is not solely dependent on atherogenic lipoproteins, but it is based on the balance between atherogenic and atheroprotective lipoproteins.[22] The existing focus on LDL as the primary cause in atherogenesis is now diverted by the more efficient ratio of the lipid parameters LDL/HDL ratio.[23]

One-unit increase in the LDL/HDL ratio is associated with a 75% increase in the risk of MI.[24] The LDL/HDLC ratio is a better predictor of dyslipidemia in assessing the risk of heart disease than LDLC alone. The ratios of LDLC/HDLC reflect the movement of cholesterol by entry and depart in the arterial intima.[25] Several studies have shown that the LDLC/HDLC ratio is not affected by dietary cholesterol.[26],[27]

This study suggests that the levels of inflammatory markers (CRP and IL-6) were relatively higher in SCH patients than the control group and they were positively correlated with TSH level in SCH group. Studies have shown elevated levels of CRP in SCH patients,[28],[29] which were positively correlated with TSH concentration.[30]

CRP is a strong predictor of cardiovascular risk. It is a marker of the underlying pro-inflammatory process of atherosclerosis. Duntas and Wartofsky suggested that SCH has been strongly associated with cardiovascular risk along with abnormal CRP.[31] Vayá et al. supported this study by reporting that CRP level was significantly higher in SCH.[32] IL-6, a pro-inflammatory cytokine, indirectly promotes atherogenesis by increasing hepatic production of CRP.[33] Significantly higher concentration of IL-6 in SCH patients in this study was supported by Taddei et al.[34] and Türemen et al.[35] IL-6 release is stimulated by TSH in adipocytes.[36]

  Conclusion Top

From this study, it is concluded that SCH patients are associated with dyslipidemia and increased inflammatory markers which may result in the future development of cardiovascular risk. According to the American Thyroid Association, there is a recommendation of routine screening of both sexes at 35 years of age, thereafter, every 5 years for the early diagnosis of SCH. Further studies are also required for a general assumption on the aspects that correlation between obesity and variations of normal thyroid function exists or not with more focus on mechanistic prospects.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1], [Table 2]


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