according to the american thyroid association ( ata ) guidelines , a thyroid nodule ( tn ) is a discrete lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma . palpable thyroid nodules occur in 48% of the population , but nodules incidentally found by ultrasound ( us ) have a prevalence of 1367% . about 5% of the clinically apparent thyroid nodules are malignant , while nonpalpable nodules have the same risk of malignancy as palpable nodules of the same size . actually , the proportion of malignant nodules is higher , which reaches 515% [ 4 , 5 ] . with the wider use of neck imaging , the incidence of thyroid nodules has increased by up to 67% in recent decades , which means that we might face increasing prevalence of thyroid cancer in the near future . previous studies have shown the associations between tn and iodine level [ 6 , 7 ] and thyroid function parameters [ 8 , 9 ] . it is reported that the level of serum thyroxine is higher in individuals with tn than those without tn , and the level of serum thyroid stimulating hormone ( tsh ) is lower in individuals with tn [ 8 , 9 ] . with the development of westernized lifestyles in china , especially in its eastern regions , obesity and metabolic diseases have already become serious health problems . increased attention has been given to the relationship between thyroid function and the components of metabolic syndrome ( mets ) . it has been reported that free tetraiodothyronine ( ft4 ) is significantly associated with the components of mets [ 10 , 11 ] . insulin resistance ( ir ) is considered the key pathophysiological mechanism of all these phenomena . previous studies have investigated thyroid function and morphological alterations in relation to obesity   or glucose metabolism . our present study is a large - sample cross - sectional and cohort study to show the relationship between the prevalence of tn and thyroid function and mets components aged 20 to 90 . it also describes the prevalence and the age- and sex - specific distribution of tn in hangzhou , zhejiang province , china . in hangzhou , the median of hangzhou residents ' urinary iodine excretion is 178.80  g / l in 2010 , which indicates this is an iodine - adequate area according to the who criteria . the samples of the present single - center study were selected from the international health care center of the second affiliated hospital of zhejiang university college of medicine . this was a cross - sectional and cohort study , which was approved by the ethics committee of the hospital . all participants provided informed consent . from january to december 2009 , a total of 19622 participants ( 12814 men , 6808 women ) voluntarily underwent general health screening in our hospital , which included thyroid us , the parameters of thyroid function , thyroid autoantibodies , and anthropometric and laboratory data . the participants came from various occupations ( factory workers , medical workers , teachers , businessmen , athletes , bank clerks , civil servants , and housewives ) . the medical history of each participant was obtained from a questionnaire , including previous diagnoses of diabetes , hypertension , thyroid diseases , liver diseases , urticaria , and lipid abnormality , whether the subject was taking antidiabetic and/or antihypertensive medication and/or lipid - lowering drugs , and whether the subject had had thyroid therapy performed including medicine and/or surgery or radiotherapy for the head and neck . participants with any of the following characteristics were excluded from the study : ( a ) individuals with history of thyroid diseases ; ( b ) individuals with history of thyroid therapy at any time including medicines ( l - thyroxine , antithyroid gland medicine ) , operation , or radiotherapy for head and neck ; ( c ) individuals with some chronic diseases ( hepatic or renal dysfunction , cardiac failure , and urticaria ) ; ( d ) pregnant or lactating women ; ( e ) individuals with significant mental or neurological disorders ( depression , epilepsy , and schizophrenia ) ; ( f ) individuals with history of other endocrine diseases or autoimmune diseases ; ( g ) individuals with history of cancer(s ) ; ( h ) individuals with iodinated contrast material exposure in the previous 6 months ; ( i ) individuals with history of taking amiodarone . in the end , 13522 participants ( 8926 men , 4596 women ) were included ; of these , 1610 individuals who underwent health screening mentioned above both in 2009 and in 2012 ( 1109 men , 501 women ) were recruited for cohort research . those participants without thyroid disease at the beginning of the cohort study , 1061 in number ( 772 men , 289 women ) , underwent a follow - up study . and the remaining 57 persons with thyroid disease such as overt or subclinical hyperthyroidism and hypothyroidism and high thyroid autoantibody titers were excluded . euthyroidism was defined as tsh ( reference range , 0.354.60  miu / l ) , free triiodothyronine ( ft3 : reference range , 3.506.50  pm ) , and ft4 ( reference range , 8.9020.60  pm ) within the normal reference range . in our hospital the reference range of total tetraiodothyronine ( tt4 ) is 60.0 to 165.0  nm and total triiodothyronine ( tt3 ) is 1.23 to 3.02  nm , thyroid peroxidase antibodies ( tpo - ab ) is 0 to 34.00  iu / ml , and thyroglobulin antibodies ( tg - ab ) is 0 to 115.00  iu / ml . diagnoses of mets in our study were made according to the international diabetes federation ( idf ) criteria in 2006 , which were defined as central obesity ( defined as a wc  90  cm and  80  cm for chinese men and women , respectively , with other values for other ethnicities ) plus any two of the following four factors : ( 1 ) raised tg level ( 1.7  mm , 150  mg / dl ) or specific treatment for this lipid abnormality ; ( 2 ) reduced high - density lipoprotein cholesterol ( hdl - c ) ( < 1.03  mm , 40  mg / dl in men and < 1.29  mm , 50  mg / dl in women ) or specific treatment for these lipid abnormalities ; ( 3 ) raised blood pressure ( bp ) ( systolic  130  mmhg or diastolic  85  mmhg ) or treatment of previously diagnosed hypertension ; ( 4 ) raised fasting plasma glucose ( fpg  5.6  mm , 100  mg / dl ) or previously diagnosed type 2 diabetes . each participant underwent a detailed physical examination , including the measurement of bp and wc . wc was measured on bare skin with a folding tape in a horizontal plane , midway between the inferior margin of the ribs and the superior border of the iliac crest in centimeters to the nearest 0.1  cm . systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) were measured twice with an automatic blood pressure monitor ( kenz pm sp-1 , suzuken co. ltd . , nagoya , japan ) on the right upper arm with the participant seated quietly for at least 5  min ; the lower value of measurement was used in the report . thyroid was assessed by two experienced physicians using b - mode us imaging ( aloka alpha10 ; aloka co , ltd , tokyo , japan ) with a 10-mhz linear array probe . the physicians performing the imaging were registered us doctors who had a professional certificate for us measurement awarded by the ministry of health of china and were blinded to the clinical and laboratory results . venous blood samples were collected using routine methods between 0700  h and 0930  h after overnight fasting . tt4 , ft4 , tt3 , ft3 , and tsh were measured with an advia centaur xp immunity analyzer ( siemens corporation ) and thyroid autoantibodies ( tpo - ab and tg - ab ) were measured with a roche electrochemical immunity analyzer ( e170 ) . fpg , fasting insulin , tg , and hdl - c were measured with an olympus au4500 automatic chemistry analyzer ( olympus corporation , tokyo , japan ) . the homeostasis model assessment ( homa ) index for ir ( homa - ir ) was calculated as fasting insulin ( mu / l ) times fpg ( mmol / l ) divided by 22.5 . all continuous data were expressed as the mean  sd . the spss 17.0 software package ( spss inc . , chicago , il ) was used for statistical analysis . continuous data were used by independent - sample t - tests and category data were used by  tests for percentages . the age trend of tn prevalence was evaluated by  tests to assess tendency . in the cross - sectional study , multivariate binary logistic regression analysis using the enter method was applied to assess risk factors for the prevalence of tn ( which was a dependent variable ) , with sex , age , sbp , dbp , wc , homa - ir , insulin , fpg , hdl - c , tt4 , ft4 , tt3 , ft3 , and tsh as independent variables . univariate binary logistic regression analysis using diverse covariates as adjustment factors was performed to assess the impact on different independent variables . in the cohort study , multivariate binary logistic regression analysis used the forward lr or backward lr method to assess the risk factors for forming tn . all statistical tests were two - tailed , and p values < 0.05 were considered significant . as noted , the cross - sectional study included a total of 13522 participants ( 8926 men and 4596 women ) . the prevalence of tn was 34.97% ( 33.97% for men and 36.92% for women ) . the standardized morbidity rate of tn was 33.70% ( 31.82% for men and 35.35% for women ) , which was calculated from the population distribution in china in 2009 . the prevalence of tn for women was statistically higher than for men in the age ranges 40 to 59 and > 70 and was significantly higher in the age range 50 to 59 ( 49.54% versus 40.04% ,  = 29.044 , p < 0.001 ) , and so was the prevalence over all ages (  = 11.651 , p = 0.001 ) . furthermore , the prevalence of tn increased along with increased age ( trend  test :  = 1200.33 for both sexes , p < 0.001 ;  = 515.22 for men , p < 0.001 ;  = 921.56 for women , p < 0.001 ) . as shown in figure 1(b ) , the number of mets ( + ) participants , who were selected according to the standard of the idf , was 2774 ( 2234 men , 540 women ) , and the prevalence of tn was 41.71% ( 1157/2774 ) . the number of mets (  ) participants was 10748 ( 6692 men , 4056 women ) , and the prevalence of tn was 33.23% ( 3572/10748 ) . the prevalence of tn in the mets ( + ) group was higher than that in the mets (  ) group (  = 69.63 , p < 0.001 ) . as shown in table 1 , there was a significant correlation between the prevalence of tn and sbp , dbp , wc , insulin , and homa - ir using univariate binary logistic regression analysis . the prevalence of tn was not related to hdl - c in the crude model , but it was significantly related to it after adjustment by sex , age , tt4 , and tsh . the prevalence of tn was significantly related to fpg in the crude model but no longer significant after the above adjustment . with multivariate binary logistic regression analysis , thyroid nodule was defined as a dependent variable , while sex , age , sbp , dbp , wc , homa - ir , fpg , hdl - c , tt4 , ft4 , tt3 , ft3 , and tsh were independent . the results were almost consistent with the univariate binary logistic regression analysis when either the enter method or the forward lr method was used ( data not shown ) ; the prevalence of tn was significantly related to sex , age , and wc ( wc : or = 1.022 , 95% ci 1.0151.029 , p < 0.001 ) . wc was an independent risk factor for the prevalence of tn . in the current cross - sectional study , the individuals with autoimmune thyroiditis were considered as an independent group . according to the inclusion and exclusion criteria of this study and the diagnostic criteria of autoimmune thyroiditis , 989 individuals were included in this group ; of these , 332 individuals were autoimmune thyroiditis with nodule and 657 ones were autoimmune thyroiditis without nodule . in the group of autoimmune thyroiditis , the prevalence of tn was not related to any metabolic component whether univariate binary logistic regression analysis or multivariate binary logistic regression analysis was used ( data not shown ) . the morbidity of mets was 26.09% in autoimmune thyroiditis positive group and 17.37% in autoimmune thyroiditis negative group (  = 46.25 , or = 1.678 , 95% ci , 1.444~1.951 , and p < 0.001 ) . then , a multivariate binary logistic regression analysis was used : the impacts of autoimmune thyroiditis on mets were fbg ( or = 0.538 , 95% ci , 0.538~0.828 , and p < 0.001 ) , tg ( or = 0.780 , 95% ci , 0.651~0.935 , and p = 0.007 ) , and hdl ( or = 5.465 , 95% ci , 4.621~6.464 , and p < 0.001 ) . the morbidity of tn was 33.57% in autoimmune thyroiditis positive group and 34.97% in autoimmune thyroiditis negative group (  = 0.799 , p = 0.371 ) . the 1061 participants without thyroid disease in 2009 ( 772 men , 289 women ) were enrolled in the cohort study . the results of follow - up were shown in table 2 . for both men and women the prevalence of tn in 2012 was higher than that in 2009 ( 43.13% versus 33.97% for men , p < 0.001 ; 42.56% versus 36.92% for women , p = 0.006 ) . we compared the mean value by age and by wc between the follow - up group and the total population group , which included 13522 individuals in 2009 . there were no statistical differences ( age : 48.02  9.04 versus 48.32  9.84 , t = 1.008 , and p = 0.293 ; wc : 85.94  9.24 versus 85.67  9.40 , t = 0.884 , and p = 0.377 ) . the proportion of women was statistically different between the follow - up group and the total population group ( the proportion for women : 27.24% versus 33.99% , c ) . like the prevalence of tn in 2009 , the morbidity rates of tn in 2012 for both men and women gradually increased along with increasing age . we then studied whether the mets components of the participants in 2009 were responsible for the prevalence of tn in the follow - up . we found that the individuals with larger wc in 2009 were more inclined to suffer from tn in 2012 ( rr = 1.422 , p = 0.007 ) ( table 3 ) . we then analyzed whether the dynamic changes in the mets components contributed to the forming of tn . the gradually increasing tg level was a risk factor for new tn ( rr = 1.001 , p = 0.035 ) . it was also consistent whether the forward lr method or the backward lr method was used in the multivariate binary logistic regression analysis ( table 4 ) . 466 of the left individuals without diabetes ( with a number of 1023 ) developed thyroid nodule . there was no significant difference between the group with diabetes and the group without it (  = 0.049 , p = 0.852 ) . among all individuals without thyroid disease in 2009 , it was eventually found in the process of follow - up that 7 out of 1061 participants suffered from thyroid cancer ( 0.66% ) . our study showed that the prevalence of tn in mets ( + ) individuals was higher than that in mets (  ) individuals and that wc was an independent risk factor for tn . recently , more attention has been paid to the correlation between mets or its components and thyroid function and its volume . they thus conclude that the thyroid gland might be one of the  victims  of the insulin resistance syndrome . as defined in the idf criteria , central obesity is the core of mets , and ir is the key mechanism of mets . show that insulin receptors , once expressed at a sufficient level , signal a ( co)mitogenic cascade as efficiently as insulin - like growth factor-1 ( igf-1 ) receptors . we showed by univariate logistic analysis that both plasma insulin level and homa - ir were correlated with tn . the sympathetic nerve activity in individuals with central obesity is higher than that in individuals with peripheral obesity . elevation in the serum level of ft3 , which is one of the calorific hormones , is probably a compensatory mechanism for central accumulation of fat . the expression of lipogenic enzyme is mediated by t3 through the  subunit of the thyroxine receptor , which strengthens the accumulation of lipid droplets and is significantly responsible for forming and maintaining mature fat . therefore , sympathetic nerves passageway for central obesity is related to thyroid . as for the group of autoimmune thyroiditis , the prevalence of tn was not related to any metabolic component . this result indicates that autoimmune pathway might be one of mechanisms of tn forming , and autoimmunity might play a more important role than metabolism does in the tn forming process in this group . the size of the group of autoimmune thyroiditis might be one of the probable factors that influence the conclusion . in the current cohort study , we found both larger wc and gradually increasing tg level were risk factors for new tn . individuals with increasing tg levels in plasma are more inclined to develop central obesity and then suffer from larger wc . both our cross - sectional study and cohort study demonstrated that the larger wc was an independent risk factor for tn . as for the morbidity rate of thyroid cancer in the follow - up process , the size of the samples was too small to confirm that . a large - sample study is therefore recommended to confirm the correlation between thyroid cancer and mets . the previous study suggested that the tn prevalence is higher in women than in men . in the current study the difference existed mainly in the age range 40 to 59 . as we all know , women in this age range were menopausal . this phenomenon suggested that disorder of internal sex hormones might be responsible for the formation of tn . the wave of sex hormone binding globulin ( shbg ) might play an important role in this process [ 29 , 30 ] . our data indicates that the prevalence of tn in both men and women increases gradually with age , which is consistent with previous studies [ 31 , 32 ] . middle and elderly women have higher incidence of tn than men . there were some limitations to this study . firstly , there was lack of data regarding the mean volume of the thyroid glands and the size of thyroid nodules . secondly , no data from cytological and/or histopathological analyses of each tn was available for many participants as they refused fine needle aspiration investigations . thirdly , the participants did not come from the randomly selected samples , who voluntarily underwent general health screening and voluntarily participated in this cross - sectional study . however , with the large sample size and broad distribution of occupations in this study , our data could , to some degree , represent the general population . although the present study did not concern the other ethnicities , we researched some similar results which had been reported in korea , argentina , and turkey . the prevalence of tn in the mets ( + ) group is higher than in the mets (  ) group . there is a significant relationship between wc and the prevalence of tn , independently of age , gender , blood pressure , fasting glucose , hdl , insulin , and homa - ir . both the larger wc and the increasing tg are risk factors for forming thyroid nodules . the results of this study indicate that maintaining wc and tg in a suitable range might be helpful in decreasing the prevalence of tn .
objective . the association between thyroid nodule ( tn ) prevalence and metabolic syndrome ( mets ) has only rarely been examined in iodine - adequate areas and needs further clarification . 
 we investigated correlations between mets and tn prevalence in the iodine - adequate area of hangzhou , china . 
 material and method . a cross - sectional study that screened and recruited individuals for cohort research 3 years later . 
 the 13522 subjects ( 8926 men , 4596 women ) were screened in 2009 for all mets components , thyroid ultrasound ( us ) , and thyroid function . 
 cohort research recruited 1610 subjects who were screened in both 2009 and 2012 , of whom 1061 underwent follow - up research . 
 results . 
 the prevalence of tn was higher in the mets ( + ) group than in the mets (  ) group ( 2 = 69.63 , p < 0.001 ) and higher in women than in men ( 2 = 11.65 , p = 0.001 ) . 
 waist circumference ( wc ) was positively related to the prevalence of tn ( or = 1.022 , p < 0.001 ) . 
 individuals with greater wc in 2009 were more likely to suffer from tn in 2012 ( rr = 1.434 , p = 0.024 ) . 
 elevated triglyceride level was a risk factor for developing new tn ( rr = 1.001 , p = 0.035 ) . conclusion . 
 both greater wc and elevated triglycerides are risk factors for new tn in this iodine - adequate area in china .