thyroid diseases are among the most common endocrinological disorders . depending on the levels of thyroid hormones , it can also be classified as subclinical ( normal thyroid stimulating hormone - tsh ) or clinical ( abnormal tsh ) . disturbances in thyroid metabolism affect various organs such as the heart , vessels , and kidney [ 16 ] . with altered thyroid functions , changes in oxygen demand , the contractility of the heart , cardiac output , and systemic vascular resistance lead to a hectic environment and worsening cardiovascular outcomes [ 79 ] . carotid intima media thickness ( ca - imt ) measurement by doppler usg is a validated method to determine extent of atherosclerosis [ 10 , 11 ] . age , male sex , smoking , diabetes , hypertension , and dyslipidemia are among the well - known risk factors for atherosclerosis . also , several other risk factors such as obesity , sedentary lifestyle , high hs - crp , homocysteine , lipoprotein , and plasminogen activator inhibitor 1 ( pai-1 ) have been linked to atherosclerotic cardiovascular diseases . accelerated atherosclerosis is well known in autoimmune rheumatic diseases compared to other autoimmune diseases such as thyroid autoimmunity [ 13 , 14 ] . thyroid hormones via blood vessel dilatation , production of vasodilator molecules , inhibition of angiotensinogen ii receptor expression , and its signal transduction regulate endothelial function and vascular homeostasis and have anti - atherosclerosis effects [ 1518 ] . regarding thyroid hormones , both clinical and subclinical hypothyroidism has been linked to atherosclerosis [ 19 , 20 ] . moreover , it has been shown that thyroid hormone replacement therapy leads to regression of subclinical hyperthyroidism [ 2124 ] . a major contributor to this problem data on the association between hyperthyroidism and atherosclerosis is less clear . with this background in mind , our aim was to investigate the extent of atherosclerosis in subclinical and clinical hypo- and hyperthyroidism along with potential roles of homocysteine and pai-1 in an otherwise healthy population . of the first two patients who applied to the endocrinology outpatient clinic with symptoms and/or signs of thyroid dysfunction each day and met the inclusion and exclusion criteria below were stratified into the corresponding thyroidism groups according to their thyroid function results ( subclinical and clinical hypothyroidism , subclinical and clinical hyperthyroidism ) . group 1 included patients with high tsh and normal ft3 and ft4 levels ( subclinical hypothyroidism ) , group 2 high tsh and low ft3 and ft4 levels ( clinical hyperthyroidism ) , group 3 low tsh and normal ft3 and ft4 levels ( subclinical hyperthyroidism ) , and group 4 low tsh and now ft3 and ft4 levels ( clinical hyperthyroidism ) . inclusion criteria were to be aged between 18 and 65 years , to have thyroid hormone dysfunction assessed by laboratory findings , to have a body mass index of 2030  kg / m , to have no history of any kind of thyroid dysfunction , and not to be on thyroid hormone replacement . exclusion criteria were to have history of diabetes , hypertension , coronary artery disease , and familial hypercholesterolemia , to be on lipid lowering drugs , and to have body mass index < 20  kg / m or > 30 ft3 , ft4 , and tsh were measured by chemiluminescence method by an automated analyzer ( immulite 2000 , siemens , germany ) . normal ranges for ft3 were 1.84.2  pg / ml , for ft4 0.81.9  ng / dl , and for tsh 0.44  mu / ml . fibrinogen levels were measured nephelometrically according to the manufacturer 's protocol by using a commercially available kit on behring bcs coagulation analyzer ( dade bering , schwalbach , germany ) . plasminogen activator inhibitor 1 ( pai-1 ) activity was measured according to the manufacturers ' protocol with indirect chromogenic assay by using spectrolyse pai-1 elisa kit ( american diagnostics , usa ) . the study protocol was approved by local ethics committees and informed consent was obtained from each patient . ultrasonographic studies on common carotid arteries were carried out by gray - scale high - resolution color doppler ultrasound ( prosound ssd- 3500 sv aloka , zug , switzerland ) equipped with 12  mhz linear transducer . the same operator performed all procedures on both sides of two longitudinal images of the each common carotid artery on the morning in supine position . average of the two ca - imt ( proximal and distal ) values from each side was used to calculate mean ca - imt on each side . comparisons between two groups were assessed with the student 's unpaired t - test or mann - whitney test , as appropriate . pearson 's and spearman 's rank correlations were used to assess correlations of fibrinogen , homocysteine , hs - crp , and pai-1 with left and right ca - imt . correlation was analyzed both in the whole population except control and also in the subgroups . all statistical analyses were performed using spss , version 15 ( chicago , il , usa ) . mean ft3 , ft4 , and tsh levels were 3.02  0.67  pg / ml , 1.13  0.24  ng / ml , and 6.91  1.74  iu / ml . mean homocysteine level was 12.76  3.11  mmol / l , hs - crp 5.98  7.84  mg / l , and pai-1 52.21  31.93  ng / ml . mean ft3 , ft4 , and tsh levels were 2.52  0.92  pg / ml , 0.76  0.29  ng / ml , and 29.87  23.65  iu / ml . mean homocysteine level was 15.05  9.87  mmol / l , hs - crp 5.41  3.48  mg / l , fibrinogen 283.00  81.16  mg / dl , and pai-1 42.78  33.65  ng / ml . mean ft3 , ft4 , and tsh levels were 3.46  0.53  pg / ml , 1.33  0.18  ng / ml , and 0.12  0.09  iu / ml . mean homocysteine level was 11.93  3.72  mmol / l , hs - crp 3.80  1.72  mg / l , fibrinogen 275.37  68.42  mg / dl , and pai-1 53.83  37.21  ng / ml . mean ft3 , ft4 , and tsh levels were 6.7  3.33  pg / ml , 2.90  1.70  ng / ml , and 0.01  0.02  iu / ml . mean homocysteine level was 10.23  3.13  mmol / l , hs - crp 3.93  1.91  mg / l , fibrinogen 275.37  68.42  mg / dl , and pai-1 53.83  37.21  ng / ml . as would be expected , patients with subclinical hypothyroidism had higher bmi compared to the control ( p = 0.035 ) . comparison of the clinical and demographical parameters of the groups is shown in table 1 . serum homocysteine levels were significantly higher in hypothyroidic patients compared to the control ( p = 0.003 ) . fibrinogen levels were higher in patients with subclinical hypothyroidism compared to other groups ( p < 0.05 ) . comparison of the clinical and demographical parameters of the groups is presented in table 2 . whereas total cholesterol , ldl , and homocysteine were correlated with ca - imt , hs - crp , pai-1 , and fibrinogen were not ( figure 1 ) . the correlation of homocysteine with ca - imt was derived from the strong correlation in the clinical hypothyroidism group ( figure 1 ) . in this study , we provide , for the first time , data on the association between several novel surrogate cardiovascular markers ( hs - crp , fibrinogen , homocysteine , and pai-1 ) and ca - imt in patients with clinical / subclinical hypo- and hyperthyroidism . only homocysteine level was associated with ca - imt and this was derived from the strong association between homocysteine and ca - imt in patients with clinical hypothyroidism . reported higher levels patients with hypothyroidism compared to the controls [ 25 , 26 ] . in other studies , there was no difference in pai-1 levels in patients with subclinical hypothyroidism compared to the control [ 28 , 29 ] . in hyperthyroidic patients , higher levels in patients with hyperthyroidism were reported [ 30 , 31 ] . our results confirm no difference between hypo- and hyperthyroidism groups and also with control . also , we report that in these patients pai-1 levels are not related to ca - imt , a marker of atherosclerosis . we also did not find any association between bmi and pai-1 levels , which is proposed as a production site for pai-1 in any of the groups . hyperhomocysteinemia is proposed as a contributor to atherosclerosis by stimulating oxidation of ldl and causing endothelial dysfunction [ 3335 ] . it is suggested that levels are increased in hypothyroidic patients and are decreased in hyperthyroidic patients . also alteration of ldl in hypothyroidism makes it plausible . in the new mexico elder health survey , no difference in patients with subclinical hypothyroidism ( n = 112 ) compared to patients with tsh  4.6  mcu / ml ( 643 ) was observed . our study confirms the finding that levels are higher in clinically hypothyroidic patients compared to control and not different from the control in patients with subclinical hypothyroidism . in line with the previous literature , levels are lower in hyperthyroidic patients compared to hypothyroidic patients but are not statistically different than the control . the association between homocysteine levels and ca - imt is not clear [ 4143 ] . our results show a positive correlation between homocysteine levels and ca - imt derived from the strong correlation between these 2 parameters in patients with clinical hypothyroidism . several studies have reported a positive association between crp levels and cardiovascular events and atherosclerosis [ 4447 ] . it is suggested that crp may be a reflection of the inflammation caused by smoking , obesity , metabolic syndrome , and other classical cardiovascular risk factors [ 48 , 49 ] . various studies have reported contradicting results on association between crp levels and severity and progression of atherosclerosis [ 5053 ] . in patients with hypothyroidism data on the level of crp is contradictory [ 5458 ] . in a study by christ - crain et al . , despite no association between thyroid hormone levels and crp , levels were found higher in hypothyroidic patients , but thyroid hormone replacement did not have any effect on crp levels in patients with subclinical hypothyroidism . a similar finding was observed in the study by lee et al . in our study , levels were higher in patients with subclinical and clinical hypothyroidism compared to other groups , but yet not statistically significant . also , no relation with ca - imt was present . possible explanation for these results may be the differences in the study population , as well as the sample size . our results also confirm the previous data that crp levels are not different from controls in hyperthyroidic patients [ 60 , 61 ] . the strongest side of our study is comparison between thyroidism subgroups along with a comparison with a control . the major limitation of our study is its cross - sectional nature and measurement at one time - point . despite most of the studies in the literature have enrolled less than 30 patients in comparison studies , the number of patients in each group in our study may still be considered relatively small . a further study enrolling higher number of patients and analyzing the value of these parameters in a time - dependent manner may yield more data on this issue . as a conclusion , our results show that homocysteine and fibrinogen levels are higher in patients with clinical and subclinical hypothyroidism , respectively . homocysteine level was associated with ca - imt in patients with thyroidism , and this was derived from the strong association between homocysteine and ca - imt in patients with clinical hypothyroidism . determination of homocysteine in clinical hypothyroidic patients may provide information on the cardiovascular burden . also , therapy to reduce homocysteine levels may be an important approach in these patients to decrease the cardiovascular burden .
background . data on the relationship between homocysteine , plasminogen activator inhibitor 1 , hs - crp , fibrinogen , and carotid intima media thickness ( ca - imt ) is plenty but contradicting and the majority of the studies investigated this issue in only specific 
 thyroidism groups . 
 the aim of this paper was to investigate these relations in patients with subclinical and clinical hypo- and hyperthyroidism . 
 methods . in this cross - sectional study , 16 patients from each thyroidism group and 20 healthy cases were enrolled . 
 fibrinogen levels and plasminogen activator inhibitor 1 ( pai-1 ) activity were assessed . 
 ca - imt was determined by gray - scale high - resolution color doppler ultrasound . 
 results . 
 serum homocysteine levels were higher in hypothyroidic patients compared to the control ( p = 0.003 ) . 
 fibrinogen levels were higher in patients with subclinical hypothyroidism compared to other groups ( p < 0.05 ) . 
 there was no difference between groups regarding pai-1 . whereas total cholesterol , homocysteine , and ldl were correlated with caimt , hs - crp , pai-1 , and fibrinogen were not . in the clinical hypothyroidism group , 
 the correlation of homocysteine with ca - imt was derived from the correlation between ca - imt and homocysteine . 
 conclusions . 
 homocysteine and fibrinogen levels are higher in patients with clinical and subclinical hypothyroidism , respectively . 
 homocysteine level is associated with ca - imtonly in patients with clinical hypothyroidism .