they have significant effect on the synthesis , mobilization , and metabolism of lipids and lipoproteins .
dyslipidemia is a common metabolic abnormality in patients with thyroid disease , in either the overt or the subclinical forms of the disease .
it has been known that overt hypothyroidism is associated with premature coronary heart disease and one of the components of this assumed to be a deteriorated metabolism of atherogenic lipoproteins .
lipoprotein(a ) ( lp(a ) ) is a very large protein molecule wrapped around , and linked by a disulphide bond to , a ldl - like particle .
there is a strong relationship with lp(a ) and coronary heart disease , independent of the standard vascular risk factors .
autoimmune thyroiditis ( hashimoto thyroiditis ) is a very common disorder and it is the main reason for hypothyroidism .
there are considerable sufficient data between the overt hypothyroidism , dyslipidemia , and coronary heart disease , although there are conflicting reports on whether subclinical hypothyroidism or euthyroid autoimmune thyroid disease has any influence on the lipoprotein metabolism .
recently it was reported that thyroid autoimmunity may be an important mechanism for the occurrence of atherosclerosis   and it is well known that lp(a ) is one of the main risk factors for the atherosclerosis .
the aim of this study was to investigate the relationship of lipid parameters , lp(a ) levels , and thyroid hormones in hashimoto thyroiditis patients .
one hundred and fifty - four premenopausal female hashimoto patients with a mean age of 37.19  7.98  sd years , followed up and treated in our outpatient clinic between july 2013 and october 2013 , were enrolled in this study .
forty - eight patients had overt hypothyroidism ( age : 35.79  7.29  sd years ) , fifty patients had subclinical hypothyroidism ( age : 36.8  8.19  sd years ) , and fifty - six patients were euthyroid ( 36.3  8.11  sd years ) .
the control group consisted of 50 healthy volunteers with a mean age of 35.42  7.64  sd years .
the diagnosis of overt hypothyroidism ( oh ) was based on clinical findings , low serum free thyroxine ( ft4 ) levels , and high serum thyroid stimulating hormone ( tsh ) concentrations .
subclinical hypothyroidism ( sh ) was established in terms of tsh levels  4.2  miu / ml and normal ft4 levels .
euthyroid hashimoto ( eh ) was established as normal ft4 and tsh levels with only positive thyroid autoantibodies .
patients and controls with diabetes mellitus , current and ex - smokers , obesity ( body mass index ( bmi ) > 30 
kg / m ) , liver disease and systemic illness , excessive alcohol consumption , and a known family history of primary hyperlipidemia were excluded from the study .
none of the subjects were receiving treatment with estroprogestin therapy , diuretics ,  blockers or lipid lowering drugs , or other medications that might alter serum lipid parameters and thyroid functions .
none of the patients were receiving thyroid treatment and lipid level determinations were done on initial presentation , before the treatment . the simple index to determine insulin resistance
[ i.e. , homeostasis model assessment ( homa - r ) > or = 2.5 ] was used , and subjects who were determined to be positive for insulin resistance according to this index were also excluded .
the study was approved by local ethical committee . written informed consent was obtained from all the subjects .
chemiluminescence immunoassay was done to assess tsh ( normal 0.4 to 4.2  miu / ml ) , free thyroxine ( normal : 0.93 and 1.7  ng / dl ) , free triiodotironin ( normal : 2.54.3  ng / ml ) , and serum autoantibodies against thyroglobulin ( tgab ) ( normal : 0115  iu / ml ) and thyroid peroxidase ( tpoab ) ( normal : 034  iu / ml eclia ( modular analytics e170 ; roche diagnostics ) ) .
the measurements of total cholesterol ( total - c ) ( normal : 130200  mg / dl ) , high density lipoprotein ( hdl - c ) ( normal : > 50  mg / dl ) , low density lipoprotein ( ldl - c ) ( normal : 70130  mg / dl ) , and triglyceride ( tg ) ( normal : 60150  mg / dl ) levels were determined by enzymatic methods .
lipoprotein(a ) ( normal 030  mg / dl ) was measured in turbidimetric method by spectrophotometry ( crony , jooly 100 ) .
continuous data were expressed as the mean  sd and median and interquartile ranges , when appropriate .
one - way anova , mann - whitney u , and kruskal wallis tests were used to compare the parametric and nonparametric data of the groups .
the demographic data and the laboratory results of the entire study group are summarized in table 1 .
. however bmi was found higher in oh group than eh and controls as expected .
tsh levels were higher in oh group than the other groups ( p < 0.0001 ) .
sh patients also have higher tsh levels than the eh and control groups ( p < 0.0001 and p < 0.0001 ) .
tsh levels were in normal limits in both control group and eh group ; eh patients have slightly higher tsh values than the control group ; however no statistical difference was found ( p = 0.05 ) ( table 2 ) .
ft3 and ft4 levels were in normal limits in both eh and control groups and no difference was found in these parameters ( p = 0.13 and  p = 0.08 , resp . ) between two groups .
however , sh patients had lower ft4 and ft3 levels compared to eh ( p < 0.0001 and p = 0.002 , resp . ) and control group ( p < 0.0001 and p < 0.0001 ) .
ft3 and tf4 levels were significantly lower in oh group than the other groups ( p < 0.0001 and p <
total cholesterol , ldl - c , and tg levels were higher in total hashimoto groups than the control group ( p < 0.0001 in each ) .
oh group has higher total - c , ldl - c , and tg levels than eh and control group as expected ( p < 0.0001 ) .
oh patients also had higher total - c ( p = 0.004 ) , tg ( p = 0.01 ) , and ldl levels ( p = 0.008 ) compared to sh group . sh group had higher total - c ( p < 0.0001 ) , ldl - c ( p < 0.0001 ) , and tg levels ( p = 0.001 ) than the control group ( table 3 ) .
sh group also had higher total - c ( p = 0.02 ) levels than the eh group ; however ldl - c ( p = 0.08 ) and tg levels ( p = 0.16 ) were similar to the eh group ( table 4 ) .
on the other hand eh group has higher total - c ( p = 0.04 ) and ldl - c ( p = 0.01 ) levels but similar tg ( p = 0.05 ) levels to the control group .
lp(a ) levels were higher in total hashimoto group than the control group ( p = 0.005 ) .
oh patients had significantly higher lp(a ) levels compared to control group ( p < 0.0001 ) ; also patients with excess lp(a ) were more common in oh than the control group ( p < 0.0001 ) .
oh patients have similar lp(a ) levels to sh patients ( p = 0.39 ) and eh group ( p = 0.15 ) ; however , lp(a ) excess was more common in oh than the eh ( p = 0.01 ) group .
although lp(a ) levels were not different between oh and sh ( p = 0.86 ) group , excess lp(a ) was also similar ( p = 0.32 ) .
on the other hand sh group has similar lp(a ) levels ( p = 0.86 ) to eh group and the control group ( p = 0.07 ) . in sh group excess lp(a )
however , sh group has more lp(a ) excess than the control group ( p = 0.001 )
. moreover eh patients also have similar lp(a ) levels to control group ( p = 0.08 ) , but in eh group excess lp(a ) was more common than in the control group ( p = 0.03 ) .
lp(a ) was positively correlated with total - c ( p < 0.0001 , r = 0.41 ) , ldl - c ( p < 0.0001 , r = 0.42 ) , tg ( p = 0.001 , r = 0.22 ) , and tsh ( p = 0.003 , r = 0.20 ) and also negatively correlated with ft4 ( p = 0.003 , r = 0.20 ) .
tsh was positively correlated with total - c ( p < 0.0001 , r = 0.40 ) , ldl - c ( p < 0.0001 ,  r = 0.38 ) , and tg ( p = 0.005 ,  r = 0.19 ) .
ft4 was negatively correlated with total - c ( p < 0.0001 ,  r = 0.38 ) , ldl - c ( p < 0.0001 ,  p = 0.38 ) , and tg ( p = 0.007  r = 0.18 ) .
however , ft3 was negatively correlated with total - c ( p < 0.0001 ,  r = 0.29 ) and ldl - c ( p = 0.0001 ,  r = 0.29 ) , but no correlation was found with tg ( p = 0.138 ) and lp(a ) ( p = 0.058 ) . there was no correlation between lp(a ) levels and thyroid autoantibodies ( ( p = 0.054 , r = 0.19 ) for anti - tpo and for ( p = 0.09 ,  r = 0.23 ) anti - tg )
this cross - sectional study shows increased total - c and ldl - c , tg and lp(a ) levels in hashimoto cohort compared with controls .
lp(a ) was increased only in oh patients , although hyperlipoprotein(a)emia was more frequent in even euthyroid hashimoto patients .
hashimoto 's thyroiditis ( chronic autoimmune thyroiditis ) is the most common cause of hypothyroidism in iodine - sufficient areas of the world .
thyroid failure is seen in up to 10 percent of the population and its prevalence increases with age . in hypothyroidism major cardiovascular changes occur .
decreased cardiovascular output and cardiac contractibility , increased peripheral vascular resistance , and reduced heart rate result in cardiovascular dysfunction .
there are also significant changes in modifiable atherosclerotic risk factors such as dyslipidemia [ 8 , 9 ] .
this is due to decreased ldl receptors ' activity , resulting in decreased catabolism of ldl and idl .
moreover , a decrease in lipoprotein lipase ( lpl ) activity is found in overt hypothyroidism which decreases the catabolism of tg rich lipoproteins ; therefore oh patients showed to have increased tg levels [ 1 , 11 , 12 ] . in our cohort
oh patients had increased total - c , ldl - c , and tg levels compared to controls , in accordance with the literature . also in sh patients reported to have increased total - c and ldl - c [ 1315 ] .
in addition some studies have shown that , in sh , dyslipidemia may also be accompanied with increased tg levels [ 16 , 17 ] . in our study , total - c , ldl - c , and tg levels were higher in the sh than in the control group . interestingly , in our cohort eh patients also have increased ldl - c , total - c , and tg levels compared to the control group .
tsh levels in our eh patients were not different from the control group . however , most of eh patients ' ( 35 of 56 patients ; 62% ) tsh values were in high - normal range ( 24  ng / ml ) .
it has been recently reported that tsh levels in the upper limits of the reference range , in patients with coronary heart disease , had adverse effect on lipid profile .
reported increased total - c and ldl - c levels in subjects with high - normal tsh levels but with positive antithyroid antibodies .
also in a prospective population based study it has been shown that high tsh levels within the reference range may be associated with adverse serum lipids .
tsh levels may covary with blood pressure and lipid levels among people with apparently normal thyroid function .
similarly a recent large cohort study showed that tsh in the upper limit of the reference range ( above 2.5 
also recently reported studies showed that autoimmunity may have some effect on dyslipidemia independent of the thyroid function . in our cohort , the increased total - c and ldl - c levels in eh patients imply that autoimmunity may have some adverse effect on lipid profile independent of the tsh value .
lp(a ) is a form of ldl - c in which lp(a ) and apob are covalently bound by a disulphide bridge ; it may be particularly atherogenic and thrombogenic .
several studies have pointed out that high lp(a ) levels are associated with atherosclerotic disease , including myocardial infarction [ 23 , 24 ] .
it was shown that lp(a ) levels are increased in patients with oh and decrease after lt-4 treatment .
however , most studies to date have not found significantly elevated lp(a ) levels in patients with sh and have not demonstrated any effect of lt-4 treatment on serum lp(a ) concentrations [ 2527 ] .
it has been reported that euthyroid males and postmenopausal females with thyroid autoimmunity present with increased lp(a ) , implying the role of thyroid autoimmunity in the lp(a ) metabolism . in our study lp(a ) was increased in oh group , although lp(a ) levels were similar in sh , eh , and even in control group . however , lp(a ) excess , which we defined as lp(a ) > 30  mg / dl , was more frequent in oh group compared to other groups .
moreover the interesting point in this study , lp(a ) excess , was also more frequent in sc and even eh than the control group . according to this finding
, we may speculate that autoimmunity may have an influence on the lp(a ) metabolism , even with the normal tsh levels . in conclusion
, this study shows that , in hashimoto thyroiditis even in normal tsh values , dyslipidemia may occur and increased total - c , tg , ldl - c , and lp(a ) excess may occur , which are the potential risk factors for atherosclerosis , considering the fact that these patients should be closely followed up in terms of cardiovascular events .
 
 objective . 
 the risk of atherosclerotic heart disease is increased in autoimmune thyroiditis , although the reason is not clear . 
 lipoprotein(a ) ( lp(a ) ) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases . 
 the aim of this study is to investigate the relationship between lp(a ) levels and thyroid hormones in hashimoto patients 
 . method . 
 154 premenopausal female hashimoto patients ( 48 patients with overthypothyroid ( oh ) , 50 patients with subclinical hypothyroid ( sh ) , and 56 patients with euthyroid hashimoto to ( eh ) ) were enrolled in this study . 
 the control group consists of 50 age matched volunteers . in every group , thyroid function tests and lipid parameters with lp(a ) were measured . 
 lp(a ) excess was defined as lp(a ) > 30  mg / dl . 
 results . 
 total - c , ldl - c , tg , and lp(a ) levels were increased in hashimoto group . 
 total - c , ldl - c , and tg levels were higher in sh group than in the control group . 
 total - c and ldl - c levels were also higher in eh group compared to controls . 
 lp(a ) levels were similar in sh and eh groups with controls . 
 however , excess lp(a ) was more common in subclinical hypothyroid and euthyroid hashimoto group than in the control group . 
 conclusion . 
 the total - c and ldl - c levels and excess lp(a ) were higher even in euthyroid hashimoto patients . 
 thyroid autoimmunity may have some effect on lp(a ) and lipid metabolism . 
1. Introduction
2. Patients and Methods
3. Results
4. Discussion