subclinical hypothyroidism ( sh ) is defined as a serum thyroid - stimulating hormone ( tsh ) level above the upper limit of normal despite normal levels of serum free thyroxine . regarding the clinical importance of the disease , there is no clinical evidence related to the adverse effects or the benefits of l - thyroxine therapy for these patients . hypothyroidism is associated with lower oxygen expenditure , heat production , and basal metabolic rate . resistin is a peptide hormone synthesized by rstn gene , belonging to the relm family . during its discovery , due to its resistance to insulin resistin is secreted from adipocytes , muscle , and pancreas cells , but mainly from mononuclear cells . in animal models , resistin has been reported to be associated with insulin resistance and diabetes mellitus , but the exact function in humans is not clear . in obese patients no correlation was present between resistin and insulin sensitivity , but resistin correlated with insulin sensitivity index in obstructive sleep apnea [ 68 ] . resistin has proinflammatory cytokine properties and its role in inflammatory diseases independent of insulin resistance had been reported . resistin is reported to be an independent and strong predictor of major cardio- and cerebrovascular events . c - reactive protein ( crp ) , named after its ability to precipitate somatic c - polysaccharide of streptococcus pneumonia , is a reliable marker systemic inflammation and tissue damage . due to its wide reference range , high - sensitive measurement methods were developed for screening properties . it is used as an strong marker in inflammatory , cardiovascular , and infectious diseases . results of studies that investigated changes in crp and resistin in thyroid dysfunction are contradictory . in hypo- and hyperthyroidism , increase , decrease , or no change have been reported [ 1214 ] . in sh with subtle thyroid dysfunction , studies of the effect of normalization of thyroid - stimulating hormone levels on resistin , crp , and body composition are rare . we aimed to determine the levels of resistin and hs - crp in women with sh , and potential effects of l - thyroxine therapy on those levels . thirty - six women with sh and 27 age- and bmi - matched healthy control women were included . body weight , waist circumference ( wc ) , waist - to - hip ratio ( whr ) , fat mass ( fm ) and lean mass ( lm ) quantified by bioelectrical impedance analysis , tsh , ft4 , ft3 , total cholesterol ( tc ) , triglycerides ( tg ) , hdl - c , ldl - c , fasting glucose and insulin , levels were determined in all participants . patients with sh who offered treatment received l - thyroxine treatment for 6 months in a prospective design after which all measurements were repeated . resistin and hs - crp levels were measured from frozen samples after the completion of the study . thyroid function tests are measured using electro chemiluminescent immunoassay ( roche diagnostics indianapolis , in , usa ) . the functional sensitivity of the tsh assay was 0.014 iu / ml ( range 0.005100 iu / ml ) . patients with tsh levels between 4.2 to 10 miu / ml with normal ft4 values are accepted to have sh . plasma glucose is measured with a spectrometric analyzer with glucose oxidase method and insulin levels are measured with immunoradiometric assay immunotech irma , czech republic ) [ intraassay coefficient of variation ( cv ) 4.3% , interassay cv 3.4% ] . insulin sensitivity homa ( homeostasis model assessment ) is calculated as [ fasting plasma glucose ( mmol / l)x fasting plasma insulin]/ 22.5 . body composition is measured after an overnight fast with bioimpedance analysis using tanita ( tanita , bc-418 ma type segmental body analysis monitor , japan ) . total body fat and truncal fat percentage , fat and lean mass ( kg ) were recorded . resistin is measured with elisa from frozen samples ( biovendor , human resistin elisa , biovendor laboratorni medicina , czech republic ) ( sensitivity 0.033 ng / ml , test limit 50 ng / ml , intra - assay variation 2.83.4% , inter- assay variation 5.16.9% ) . hs - crp is measured with the highly sensitive near infrared particle immunoassay rate- method ( immageimmunochemistry systems crph test , beckman - coulter galway , ireland ) . all statistical analyses were performed using spss 13.0 ( spss , chicago , il , usa ) . student t test and paired - sample t test , mann whitney and wilcoxon tests were used to compare groups where appropriate . thirty - six women with sh and 27 healthy sex- and - age matched controls were included in the study . patients with sh had higher tsh and lower ft4 levels compared to the control group ( table 2 ) . the rest of the parameters , including resistin and hs - crp , were similar between groups . l - t4 treatment decreased tsh and increased ft4 significantly ( p<0.0001 and p<0.0001 , respectively ) , but did not change the rest of the parameters ( table 3 ) . lt4 treatment did not change either resistin or hs - crp levels ( table 4 ) . resistin levels correlated positively with hs - crp ( p=0.034 and rs=0.355 ) at the beginning of the study ( p=0.012 , rs=0.426 ; and p=0.028 , and rs=0.382 , respectively ) . basal hs - crp correlated positively with weight , bmi , waist , whr , fm and tg ( table 5 ) . resistin did not correlate with any of the parameters at the end of the study ; on the other hand , hs - crp correlated with bmi , whr , fm , tg , and homa at the end of the study ( table 6 ) . our results suggest that women with sh have similar resistin and hs - crp levels in comparison with age- and bmi - matched healthy women . sh is a unique disease because it is presented with a sole increase in tsh , but normal free thyroid hormone levels . some studies reported an increase in sh , but the rest of them could not find any change compared to control groups [ 17,19,2123 ] . we could not demonstrate a difference in hs - crp levels in women with sh compared to the control group , and treatment with lt4 did not have any effect on these parameters . in spite of the absence of any difference between the control group and patients with sh , hs - crp correlated with weight - related parameters . crp levels are closely associated with parameters of adiposity , insulin resistance , and metabolic syndrome [ 2527 ] . presence of inflammatory cells in the adipose tissue may be the cause of changes , even if we were not able to demonstrate any difference in amount of the adipose tissue . the interactions between the metabolic pathways and inflammation occurring through an activation of the adipose tissue still remains mysterious . adipokines ( leptin and adiponectin ) had been studied in sh and controversial results had been reported . there is only limited data available related to resistin , a unique molecule regarding its role in insulin sensitivity and inflammation in thyroid disorders . as a product of adipose tissue resistin plays an important role in the pathogenesis of obesity - related insulin resistance and type 2 diabetes mellitus in animal models , but its precise role in humans is debatable [ 3,3638 ] . resistin has some proinflammatory cytokine properties and plays an important role in inflammatory diseases irrespective of its role in insulin resistance . it has been suggested that resistin modulates molecular pathways that maintain cross - talk between inflammation and metabolic markers . thyroid hormone abnormalities and resistin interference has been studied in different diseases [ 14,29,3941 ] . demonstrated an increase in resistin and tsh in thyroid cancer patients during withdrawal of thyroid hormones for iodine scan , but this increase was not different from the control group . high doses of triiodothyronine did not have any effect on resistin , whereas diminished leptin and adiponectin gene expression in calorie - restricted obese rats . contrary to this , a positive correlation between resistin , ft3 , and ft4 had been documented by yaturu et al . . in a study including 43 hyperthyroid and 23 control patients , resistin levels were higher in hyperthyroid patients and decreased after restoration of the thyroid hormone levels . . showed similar results in untreated graves patients in whom resistin levels were higher compared to simple goiter and hashimoto disease patients . iglesias et al also documented higher resistin in hyperthyroidism , which was explained by an increase insulin resistance in hyperthyroidism . kaplan et al . showed short - term thyroidectomy - induced hypothyroidism did not affect adipokines . our inability to document a correlation between insulin sensitivity parameters and resistin suggests the presence of alternative pathways through which resistin plays a role . our study is a prospective study in which the same patients with sh were evaluated after they became euthyroid . the group was homogenous in terms of metabolic and adipose tissue functions because all patients were premenopausal women , although the possibility of extrapolation of this data to men is not clear . when hypothyroidism is present , changes occur in body temperature , food consumption , all parameters in glucose and lipid consumption , and energy metabolism . approximately 40% of genes expressed in adipose tissue are novel and 2030% of them can synthesize proteins . the changes in energy metabolism , even in sh status , may affect adipokine levels . the trh - tsh pathway affects fat metabolism through a complex interaction between hypothalamus , hypophysis , thyroid , and adipose tissue [ 4850 ] . with the presently available data it is impossible to form conclusions about changes in adipocytokines according to thyroid status . gender and patient characteristics , degree and duration of thyroid dysfunction , antibody concentrations , metabolic effects of other hormones , and possible effects of intermediate metabolism may all be responsible for the conflicting results related to the relationship between thyroid and adipocytokine .
backgroundsubclinical hypothyroidism ( sh ) is defined by increased thyrotropin ( tsh ) and normal free thyroxine ( ft4 ) and free triiodothyronine ( ft3 ) levels . 
 resistin is secreted from adipose tissue and is reported to be associated with insulin resistance and/or inflammation . 
 high sensitive crp ( hs - crp ) is a reliable marker of inflammation . 
 data related to levels of resistin and hs - crp in sh and the effect of l - thyroxine treatment on those is limited . 
 we aimed to determine the levels of resistin and hs - crp in women with sh , and potential effects of l - thyroxine therapy on those levels.material/methodsthirty-six patients with sh and 27 age- and bmi - matched healthy control women were included . 
 waist circumference ( wc ) , waist - to - hip ratio ( whr ) , resting energy expenditure ( ree ) , fat mass ( fm ) and lean mass ( lm ) , tsh , free t4 ( ft4 ) , free t3 ( ft3 ) , total cholesterol ( tc ) , triglycerides ( tg ) , and hdl- and ldl - cholesterol were determined in all participants . 
 patients received l - thyroxine treatment for 6 months , after which all measurements were repeated . 
 resistin and hs - crp levels were studied from frozen samples after the completion of the study.resultsthe 2 groups had similar values for wc , whr , fm , lm , tc , tg , hdl - c , ldl - c , resistin , and hs - crp at the beginning . 
 ft4 were higher , whereas tsh was lower in the control group . 
 resistin and hs - crp levels did not change after treatment . 
 hs - crp correlated with bmi and fm before and after treatment.conclusionsour results suggest that achievement of euthyroid status by replacement therapy did not change resistin or hs - crp levels in women with sh . 
 hs - crp correlated with parameters of obesity , which emphasizes the role of body weight in inflammation .