thyroid - stimulating hormone ( also known as thyrotropin , tsh ) stimulates the thyroid gland to produce thyroxine ( t4 ) and triiodothyronine ( t3 ) , which is a metabolism - stimulating hormone . tsh is synthesized and secreted by thyrotrope cells in the anterior pituitary gland and regulates the endocrine function of the thyroid gland . production and secretion of tsh is stimulated by the hypothalamus , which produces thyrotropin - releasing hormone ( trh ) . production of tsh is inhibited by somatostatin , which is also produced by the hypothalamus , and via a negative feedback loop by t3 and t4 . they have high prevalence , chronic course , significant mental and somatic comorbidity and very high personal and societal costs ( lost productivity and increased medical expenses ) . also , many patients respond poorly to medications and have frequent and disrupting relapses . finally , although several biological markers have been identified , such as cortisol   or brain derived neurotrophic factor ( bdnf ) , none of them is conclusive , partly because they are shared by different disorders . tsh also can not be used as a single biomarker of any mental disorder , but could serve as an additional biomarker for improving diagnostic or therapeutic procedures . the relation between thyroid function and mental disorders thyroid disorders , including both hypothyroidism and hyperthyroidism , may be accompanied by various neuropsychiatric manifestations , ranging from depression   and anxiety   to psychosis . hypothyroidism clinical symptoms may mimic melancholic depression and dementia , while in elderly patients hyperthyroidism may mimic depression and pseudodementia . also , tsh levels are correlated with depression severity   and hyperthyroidism may increase the risk of developing bipolar disorders . have found higher rates of panic disorder , simple phobia , obsessive  compulsive disorder , major depressive disorder , bipolar disorder and cyclothymia in thyroid patients than in the general population . these findings would suggest that the co - occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities . reported that depression was observed more frequently among individuals with subclinical ( 49.7  % ) hypothyroidism than among individuals with overt hypothyroidism ( 16.8  % ) ( p  <  0.001 ) and subclinical hypothyroidism increased the risk for a patient to present depression more than four times ( or  =  4.9 ) . in schizophrenia results of thyroid function studies rao et al .   concluded that increased dopaminergic activity affects pituitary secretory functions and may lead to reduced tsh levels . subclinical hypothyroidism may be present in treatment - naive patients with schizophrenia and treatment with antipsychotics may increase basal tsh levels , while rao et al . higher basal tsh levels may be associated with a poorer treatment response in schizophrenia , while t4 levels showed a positive correlation with the severity of illness and the degree of clinical response to neuroleptic treatment . the above findings would suggest that the co - occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities . therefore , we have carried out this study in order to investigate differences in tsh level in patients with schizophrenia , unipolar depression , bipolar depression and bipolar mania . our psychiatry clinical hospital database was screened for serum thyroid - stimulating hormone ( tsh ) level . only the first entry for each patient from inpatient care units thus , we have assumed that most patients that we included in the study were in acute phase of their disorder . we focused on patients with schizophrenia ( all subtypes ) , bipolar disorder and unipolar depression . patients were grouped under diagnostic criteria as schizophrenia ( f20 according to icd-10 , 295 according to dsm - iv ) , unipolar depression ( f31 and f32 according to icd-10 , 296.2 and 296.3 according to dsm - iv ) , bipolar disorder ( f30 and f31 according to icd-10 , 296 . according to dsm - iv ) , bipolar depression ( f31.3f31.5 according to icd-10 , 296.6 according to dsm - iv ) and bipolar mania ( f30 and f31.0f31.2 according to icd-10 , 296.0 and 296.4 according to dsm - iv ) . in our unit diagnosis is based on the icd-10 criteria , dsm - iv codes were given as reference . blood samples were drawn for all patients between 8 and 9 a.m. after 12  h overnight fast . immediately after collecting blood samples tsh serum level was determined using automatic analyzer dirui cs-400 ( dirui , china ) . for the normal range three different criteria were used : ( 1 ) the currently accepted 0.45.0  iu / ml range ; ( 2 ) the 0.33.0  iu / ml range proposed by the american association of clinical endocrinology ; and ( 3 ) the 0.42.5  iu / ml range recommended by the national academy of clinical biochemistry ( nacb ) . simple descriptive statistics ( means and standard deviations ) were generated for continuous variables . for discrete variables number of patients and percentages are given . wallis test ( for tsh level ) or one - way anova ( for age ) , intra - group differences were analyzed using wilcoxon rank - sum test . ine the study group of 1,685 patients included in the analysis there were 63.1  % women ( n  =  1,064 ) . the proportion of women in the schizophrenia group ( n  =  769 ) was 50.5  % ( n  =  388 ) , in the unipolar depression group ( n  =  652 ) was 75.8  % ( n  =  494 ) , in the bipolar disorder group ( n  =  264 ) was 68.9  % ( n  =  182 ) , in the bipolar depression group ( n  =  203 ) was 71.9  % ( n  =  146 ) and in the bipolar mania ( n  =  61 ) was 59.0  % ( n  =  36 ) . the difference between the groups in the proportion of women was significant (   =  105.01 , df  =  3 , p  <  0.001 ) , with the lowest proportion of women in the schizophrenia group . in the schizophrenia group ( n  =  769 ) there were three patients with hebephrenic subtype , 20 patients with paranoid schizophrenia and catatonic symptoms , four with residual schizophrenia and two with simple - type schizophrenia . these subgroups were to small to include them into separate analysis and therefore we decided to combine all patients with schizophrenia into one group . figure  1 shows the total number of patients and stratification of patients into diagnostic groups.fig . 1total number of patients and stratification of patients into diagnostic groups total number of patients and stratification of patients into diagnostic groups the age ( mean    standard deviation ) of the study group was 46.4    19.8  years . mean age in the subgroups was : schizophrenia 40.0    16.2 , unipolar depression 52.1    21.7 , bipolar depression 52.8    18.4 , bipolar mania 45.3    19.8  years . one - way anova showed that there were significant age differences between the groups ( f  =  56.72 , df  =  3 , p  <  0.001 ) . post hoc comparisons using the bonferroni test showed that patients with unipolar- and bi - polar depression groups were significantly older ( p  <  0.001 for both groups ) . age distribution in the study sample is shown in table  1.table  1age distribution in the study samplediagnosisage categorytotal [ n ( % ) ] < 2020404060>60schizophrenia  men262487631381 ( 49.5 )  women3117211570388 ( 50.5 )  total57420191101769unipolar depression  men24205757158 ( 24.2 )  women9334165202494 ( 75.8 )  total11754222259652bipolar disorder  men1124212682 ( 31.1 )  women8436170182 ( 68.9 )  total19678296264bipolar depression  men516122457 ( 28.1 )  women4355057146 ( 71.9 )  total9516281203bipolar mania  men689225 ( 41.0 )  women48111336 ( 59.0 )  total1016201561 age distribution in the study sample we have found several significant correlations between age and tsh level . in the whole study group tsh level was negatively correlated with age ( r  =  0.23 , p  <  0.001 ) , but not in the bipolar mania ( p  =  0.07 ) group . weak correlations with age have been found in the schizophrenia ( r  =  0.21 , p  <  0.001 ) , unipolar depression ( r  =  0.23 , p  <  0.001 ) , bipolar depression ( r  =  0.25 , p  =  0.002 ) and bipolar disorder ( r  =  0.21 , p  =  0.005 ) groups . for the whole study group there was no difference between men and women for tsh levels ( 1.58    1.39 vs. 1.77    2.82  iu / ml , z  =  1.13 , p  =  0.25 ) . mean serum tsh level in the study groups was : schizophrenia 1.71    1.49  iu / ml , unipolar depression 1.63    1.95  iu / ml , bipolar disorder group 1.86    4.58  iu / ml , bipolar depression 2.00    5.18  iu / ml , bipolar mania 1.38    1.17  iu / ml , see fig . 2 . there was a significant difference between the serum level of tsh between patients with schizophrenia , unipolar depression , bipolar depression and bipolar mania ( h  =  11.58 , df  =  3 , p  =  0.009 ) . the highest level of tsh was found in the bipolar depression group ( 2.00    5.18  iu / ml ) and the lowest in patients with bipolar mania ( 1.38    1.17  iu / ml ) . the difference was also significant for the subgroup of men ( h  =  9.89 , df  =  3 , p  =  0.019 ) , but not for women ( h  =  4.93 , df  =  3 , p  =  0.17 ) . when patients with bipolar mania or depression were combined into one group ( bipolar disorder ) , there were also significant inter - group differences between patients with schizophrenia , unipolar depression and bipolar disorder ( h  =  8.62 , df  =  2 , p  =  0.013 ) . the lowest level was in patients with unipolar depression ( 1.63    1.95  iu / ml ) and the highest level was in patients with bipolar disorder ( 1.86    4.58  iu / ml ) , see fig . the difference was also significant for the subgroup of men ( h  =  7.49 , df  =  2 , p  =  0.023 , but not for women ( h  =  4.17 , df  =  2 , p  =  0.12).fig . 2mean tsh levels [ iu / ml ] with standard error in subjects with schizophrenia , unipolar depression , bipolar depression and bipolar maniafig . 3mean tsh levels [ iu / ml ] with standard error in subjects with schizophrenia , unipolar depression and bipolar disorder mean tsh levels [ iu / ml ] with standard error in subjects with schizophrenia , unipolar depression , bipolar depression and bipolar mania mean tsh levels [ iu / ml ] with standard error in subjects with schizophrenia , unipolar depression and bipolar disorder table  2 shows sex distribution in diagnostic groups for normal ranges of tsh . evaluation of the 0.45.0  iu / ml normal range revealed significant differences between diagnostic groups with regard to serum tsh categories (   =  16.29 , df  =  6 , p  =  0.012 ) . when patients with bipolar depression and bipolar mania were combined into one group ( bipolar disorder ) the difference was also significant (   =  14.78 , df  =  4 , p  =  0.005 ) . the overall rate of being above or below the normal range was 7.9  % for patients with schizophrenia , 13.9  % for patients with unipolar depression , 10.8  % for patients with bipolar disorder , 12.2  % for patients with bipolar depression , and 11.4  % for patients with bipolar mania . the rate of patients being below the normal range was the highest in patients with unipolar depression ( 11.0  % ) , while the rate of patients being above the normal range was the highest in patients with bipolar depression ( 4.4  % ) .with the exception of bipolar mania , the rate of patients being below or above the normal range was higher in women ( where it was higher only in patients with tsh level above the normal range ) . there was a significant difference between age of patients with tsh level below or above normal range ( below 56.3    17.6  years , normal range 45.5    19.8  years , above 48.2    19.8  years , f  =  19.26 , df  =  2 , p  <  0.001 ) . post hoc analysis showed that patients with tsh level below the normal range were significantly older comparing to patients with tsh level above ( p  =  0.042 ) or within the normal range ( p  <  0.001).table  2sex distribution in diagnostic groups for normal ranges of tshdiagnosistsh category [ ( iu / ml ) n ( % ) ] < 0.40.45.0>5.0<0.30.33.0>3.0<0.40.42.5>2.5schizophrenia44 ( 5.7)706 ( 91.8)19 ( 2.5)24 ( 3.1)659 ( 85.7)86 ( 11.2)44 ( 5.7)597 ( 77.6)128 ( 16.6 )  men20 ( 5.2)354 ( 92.9)7 ( 1.8)8 ( 2.1)331 ( 86.9)42 ( 11.0)20 ( 5.2)300 ( 78.7)61 ( 16.0 )  women24 ( 6.2)352 ( 90.7)12 ( 3.1)16 ( 4.1)328 ( 84.5)44 ( 11.3)24 ( 6.2)297 ( 76.5)67 ( 17.3)unipolar depression72 ( 11.0)561 ( 86.0)19 ( 2.9)47 ( 7.2)541 ( 83.0)64 ( 9.8)72 ( 11.0)482 ( 73.9)98 ( 15.0 )  men15 ( 9.5)141 ( 89.2)2 ( 1.3)10 ( 6.3)136 ( 86.1)12 ( 7.6)15 ( 9.5)123 ( 77.8)20 ( 12.7 )  women57 ( 11.5)420 ( 85.0)17 ( 3.4)37 ( 7.5)405 ( 82.0)52 ( 10.5)57 ( 11.5)359 ( 72.7)78 ( 15.8)bipolar disorder22 ( 8.3)232 ( 87.9)19 ( 2.5)15 ( 5.7)214 ( 81.1)35 ( 13.3)22 ( 8.3)191 ( 72.3)51 ( 19.3 )  men6 ( 7.3)74 ( 90.2)7 ( 1.8)3 ( 3.7)72 ( 87.8)7 ( 8.5)6 ( 7.3)64 ( 78.0)12 ( 14.6 )  women16 ( 8.8)158 ( 86.8)12 ( 3.1)12 ( 6.6)142 ( 78.0)28 ( 15.4)16 ( 8.8)127 ( 69.8)39 ( 21.4)bipolar depression16 ( 7.8)178 ( 87.7)9 ( 4.4)12 ( 5.9)162 ( 79.8)29 ( 14.3)16 ( 7.8)145 ( 71.4)42 ( 20.7 )  men2 ( 3.51)53 ( 93.0)2 ( 3.5)1 ( 1.7)50 ( 87.7)6 ( 10.5)2 ( 3.51)45 ( 78.9)10 ( 17.5 )  women14 ( 9.59)125 ( 85.6)7 ( 4.8)11 ( 7.5)112 ( 76.7)23 ( 15.7)14 ( 9.59)100 ( 68.5)32 ( 21.9)bipolar mania6 ( 9.8)54 ( 88.5)1 ( 1.6)3 ( 4.9)52 ( 85.2)6 ( 9.8)6 ( 9.8)46 ( 75.4)9 ( 14.7 )  men4 ( 16.0)21 ( 84.0)02 ( 8.0)22 ( 88.0)1 ( 4.0)4 ( 16.0)19 ( 76.0)2 ( 8.0 )  women2 ( 5.6)33 ( 91.7)1 ( 2.8)1 ( 2.8)30 ( 83.3)5 ( 13.9)2 ( 5.6)27 ( 75.0)7 ( 19.4 ) sex distribution in diagnostic groups for normal ranges of tsh evaluation of the 0.33.0  iu / ml normal range revealed significant differences between diagnostic groups with regard to serum tsh categories (   =  15.55 , df  =  6 , p  =  0.016 ) . when patients with bipolar depression and bipolar mania were combined into one group ( bipolar disorder ) the difference was also significant (   =  14.45 , df  =  4 , p  =  0.006 ) . the overall rate of being above or below the normal range was 14.3  % for patients with schizophrenia , 17.0  % for patients with unipolar depression , 19.0  % for patients with bipolar disorder , 20.2  % for patients with bipolar depression , and 14.7  % for patients with bipolar mania . the rate of patients being below the normal range was the highest in patients with unipolar depression ( 7.2  % ) , while the rate of patients being above the normal range was the highest in patients with bipolar depression ( 14.3  % ) .with the exception of bipolar mania , the rate of patients being below or above the normal range was higher in women ( where it was higher only in patients with tsh level above the normal range ) . there was a significant difference between age of patients with tsh level below or above normal range ( below 57.9    17.1  years , normal range 46.1    19.8  years , above 43.7    19.3  years , f  =  16.50 , df  =  2 , p  <  0.001 ) . post hoc analysis showed that patients with tsh level below the normal range were significantly older comparing to patients with tsh level above ( p  <  0.001 ) or within the normal range ( p  <  0.001 ) . evaluation of the 0.42.5  iu / ml normal range revealed significant differences between diagnostic groups with regard to serum tsh categories (   =  16.69 , df  =  6 , p  =  0.010 ) . when patients with bipolar depression and bipolar mania were combined into one group ( bipolar disorder ) the difference was also significant (   =  15.36 , df  =  4 , p  =  0.004 ) . the overall rate of being above or below the normal range was 22.3  % for patients with schizophrenia , 26.0  % for patients with unipolar depression , 27.6  % for patients with bipolar disorder , 28.5  % for patients with bipolar depression , and 24.5  % for patients with bipolar mania . the rate of patients being below the normal range was the highest in patients with unipolar depression ( 11.0  % ) , while the rate of patients being above the normal range was the highest in patients with bipolar depression ( 20.7  % ) .with the exception of bipolar mania , the rate of patients being below or above the normal range was higher in women ( where it was higher only in patients with tsh level above the normal range ) . there was a significant difference between age of patients with tsh level below or above normal range ( below 56.3    17.6  years , normal range 46.4    19.7  years , above 42.0    20.2  years , f  =  24.58 , df  =  2 , p  <  0.001 ) . post hoc analysis showed that patients with tsh level below the normal range were significantly older comparing to patients with tsh level above ( p  <  0.001 ) or within the normal range ( p  <  0.001 ) , while patients with tsh level above the normal range were younger than patients with tsh level within the normal range ( p  =  0.002 ) . patients were divided into four group : 20 , > 20  years and 40 , > 40  years and 60  years and > 60  years . age distributions of tsh level are shown in table  3 for patients with schizophrenia , in table  4 for patients with unipolar depression , in table  5 for patients with bipolar disorder , in table  6 for patients with bipolar depression and in table  7 for patients with bipolar mania . there were significant differences between tsh level in age groups of schizophrenia patients ( p  <  0.001 ) , in men ( p  <  0.001 ) but not in women ( p  =  0.077 ) . comparing men with women , tsh level was higher in women only in the subgroup of patients aged 4060 ( p  =  0.008 ) , while other differences were not significant . in patients with unipolar depression there were significant differences between tsh level in age groups ( p  <  0.001 ) , both in men ( p  <  0.001 ) and in women ( p  <  0.001 ) . comparing men with women , tsh level was higher in women only in the subgroup of patients aged > 60 ( p  =  0.002 ) , while other differences were not significant . in patients with bipolar disorder there were significant differences between tsh level in age groups ( p  =  0.026 ) , in women ( p  =  0.031 ) but not in men ( p  =  0.23 ) . there were no differences in age groups between men and women with bipolar disorder . in patients with bipolar depression there were significant differences between tsh level in age groups ( p  =  0.014 ) but not in men ( p  =  0.06 ) and in women ( p  =  0.19 ) . there were no differences in age groups between men and women with bipolar depression . in patients with bipolar mania there were no significant differences between tsh level in age groups ( p  =  0.64 ) , also in men ( p  =  0.11 ) and in women ( p  =  0.07 ) . comparing men with women , tsh level was higher in women only in the subgroup of patients aged 2040 ( p  =  0.012 ) , while other differences were not significant ( table  7 ) . table  3mean tsh level ( in iu / ml ) in patients with schizophreniatotalage category 
 p 
 < 2020 - 4040 - 60>60men1.68    1.571.93    0.901.75    1.321.42    2.301.64    1.72h  =  29.62 
 p  <  0.001women1.73    1.401.84    1.031.81    1.361.62    1.561.63    1.38h  =  6.84 
 p  =  0.077total1.71    1.491.88    0.961.77    1.331.54    1.891.63    1.48h  =  27.56 p  <  0.001 
 p 
 z  =    0.87 
 p  =  0.38z  =  0.68 
 p  =  0.49z  =    0.57 
 p  =  0.56z  =    2.66 
 p  =  0.008z  =    0.42 
 p  =  0.66 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum testtable  4mean tsh level ( in iu / ml ) in patients with unipolar depressiontotalage category 
 p 
 < 2020404060>60men1.39    0.982.20    1.191.72    1.041.37    0.910.96    0.63h  =  31.18 
 p  <  0.001women1.71    2.171.98    1.101.59    1.221.86    3.341.47    1.22h  =  26.72 
 p  <  0.001total1.63    1.952.03    1.121.64    1.151.74    2.921.36    1.14h  =  48.46 
 p  < 0.001 
 p 
 z  =    1.49 
 p  =  0.13z  =  1.03 
 p  =  0.30z  =  0.66 
 p  =  0.51z  =    0.04 
 p  =  0.96z  =    3.04 
 p  =  0.002 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum testtable  5mean tsh level ( in iu / ml ) in patients with bipolar disordertotalage category 
 p 
 < 2020 - 4040 - 60>60men1.43    1.121.74    1.021.53    1.361.59    1.281.09    0.70h  =  4.21 
 p  =  0.23women2.05    5.462.73    2.281.94    1.221.49    1.372.51    8.63h  =  8.87 
 p  =  0.031total1.86    4.582.16    1.691.80    1.271.52 7.39h  =  9.28 
 p  =  0.026 
 p 
 z  =    0.89 
 p  =  0.37z  =    0.57 
 p  =  0.56z  =    1.73 
 p  =  0.08z  =  0.48 
 p  =  0.62z  =    0.86 
 p  =  0.38 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum testtable  6mean tsh level ( in iu / ml ) in patients with bipolar depressiontotalage category 
 p 
 < 2020404060>60men1.56    1.201.90    0.871.84    1.471.84    1.581.15    0.69h  =  4.71 
 p  =  0.19women2.17    6.053.54    2.591.93    1.271.63    1.472.71    9.54h  =  7.11 
 p  =  0.06total2.00    5.182.63    1.911.90    1.321.67    1.482.25    8.02h  =  10.63 
 p  =  0.014 p 
 z  =    0.28 
 p  =  0.77z  =    0.98 
 p  =  0.32z  =    0.44 
 p  =  0.65z  =  0.39 
 p  =  0.69z  =    0.45 
 p  =  0.64 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum testtable  7mean tsh level ( in iu / ml ) in patients with bipolar maniatotalage category 
 p 
 < 20204040 - 60>60men1.16    0.891.61    1.190.91    0.861.26    0.630.33    0.35h  =  5.94 
 p  =  0.11women1.54    1.311.92    1.922.01    1.040.90    0.421.66    1.66h  =  6.77 
 p  =  0.07total1.38    1.171.74    1.431.46    1.081.06    0.541.48    1.61h  =  1.66 
 p  =  0.64 
 p 
 z  =  1.07 
 p  =  0.28z  =  0.00 
 p  =  1.00z  =  2.52 
 p  =  0.012z  =  1.17 
 p  =  0.23z  =  1.69 
 p  =  0.09 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum test mean tsh level ( in iu / ml ) in patients with schizophrenia 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum test mean tsh level ( in iu / ml ) in patients with unipolar depression 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum test mean tsh level ( in iu / ml ) in patients with bipolar disorder 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum test mean tsh level ( in iu / ml ) in patients with bipolar depression 
 inter age - subgroups , kruskal wallis test 
 men versus women , wilcoxon rank - sum test mean tsh level ( in iu / ml ) in patients with bipolar mania 
 inter age - subgroups , kruskal the aim of this retrospective , cross - sectional , naturalistic study was to investigate differences in tsh level in acute phase of schizophrenia , unipolar depression , bipolar depression and bipolar mania . we have analyzed tsh level in age subgroups of diagnostic groups , as well as distribution of results within and outside three different normal ranges . we have found that patients with bipolar disorder have the highest level of tsh , while the lowest level was seen in patients with unipolar depression . when patients with bipolar mania and bipolar depression were analyzed as separate groups , we have found that patients with bipolar depression had the highest level of tsh , while the lowest level was found in patients with bipolar mania . this difference can not be explained only by differences in age between study groups since patients with unipolar- and bi - polar depression were significantly older comparing to other study groups . the direction of tsh abnormalities ( to hypothyroidism or hyperthyroidism ) depended on the normal range used for analysis . when the widest normal range was used ( 0.45.0  iu / ml ) the abnormality was mainly in the direction of hyperthyroidism , while for other two ranges the abnormality was mainly in the direction of hypothyroidism . these observations were independent on diagnostic group and sex , with the exception of patients with bipolar mania , but this group was much smaller and thus under representative comparing to other diagnostic groups . patients with bipolar depression had the highest rate of being above or below normal range of tsh level . with the exception of bipolar mania , in all diagnostic groups there were differences in tsh level between predefined age groups . in patients with schizophrenia and unipolar depression older patients had the lowest level of tsh . in patients with bipolar disorder and bipolar depression lowest tsh levels were in patients aged 4060 ( there were no significant differences between tsh level in age groups of patients with bipolar mania ) . this is contradictory to the results of the population - based national health and nutrition examination survey ( nhanes ) , where positive correlation between age and tsh level was found in a large ( n  =  17,353 ) sample . this observation might be explained by the fact that our study sample has various potential risk factors of thyroid dysfunction , associated with clinical diagnosis and resulting from treatment . on the other hand , our results are consistent with results of the german study , which show that age was the only independent factor and was significantly inversely associated with tsh . meta - analysis of thyroid dysfunctions in europe showed that the prevalence of undiagnosed hypothyroidism was 4.94  % and the prevalence of undiagnosed hyperthyroidism was 1.72  % . the prevalence of both previously diagnosed and undiagnosed hypothyroidism and hyperthyroidism was 3.05 and 0.75  % , respectively . for depression , 14  % of patients are found to have overt hypothyroidism while subclinical hypothyroidism occurs in 440  % of these patients . in 868 elderly psychiatric long - term care patients 10.8  % had elevated tsh , 8  % in those with a prior diagnosis of hypothyroidism , while low tsh levels were found in 0.07  % patients . according to our data the prevalence of clinical and subclinical hypothyroidism in the study sample may be as high as 4.420.7  % ( in patients with bipolar depression , for normal range 0.45.0 and 0.42.5  iu / ml , respectively ) . as reported by cole et al . patients with bipolar depression and with optimal thyroid profile experienced remission 4  months faster than the remainder of the study group . this study provides further evidence that patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range and nearly three - quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response . regarding hyperthyroidism , the prevalence of clinical and subclinical hyperthyroidism in the study sample may be as high as 7.211.0  % ( in patients with unipolar depression , for normal range 0.33.0 and 0.42.5 or 0.45.0  iu / ml , respectively ) . the rate of low tsh in patients with bipolar disorder ( tsh  <  0.4  iu / ml , 8.3  % ) in this study was higher than previously reported ( 6.2  % ) . as noted by these authors , since we have no data on free t4 level , our interpretation of tsh level might be inaccurate and can be used only as rough estimations . moreover , it should be noted that a state of  brain hypothyroidism  was reported in patients with depression . this state of brain hypothyroidism occurs in systemic euthyroidism and may result from a defect of thyroid hormone receptor or impaired thyroid hormone transporter . in the large nhanes study mean serum tsh was 1.50 iu / ml and was higher in females than males . comparing to this result , in our study sample mean serum tsh levels were higher in patients with schizophrenia ( 1.71 iu / ml ) , unipolar depression ( 1.63 iu / ml ) , bipolar disorder ( 1.86 iu / ml ) , bipolar depression ( 2.00 iu / ml ) and lower in patients with bipolar mania ( 1.38 iu / ml ) . as above , this may also be explained by the fact that our study sample was not population - based and it reflects associations between mental disorders and thyroid dysfunctions . in conclusion , our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders ( both unipolar and bipolar ) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions . this also confirms the need to monitor tsh level regularly in patients with all types of mood disorders . when low normal tsh ranges are used ( 0.3 - 3.0 or 0.4 - 2.5 iu / ml ) , we could detect subclinical thyroid dysfunctions in higher number of highly susceptible patients ( lowering the normal tsh range from 0.4 - 5.0 to 0.4 - 2.5 caused a five to eight - fold increase in the number of patients who had tsh levels outside the normal range ) . this is particularly important in the light of recommendations of the american association of clinical endocrinologists , which state that  the diagnosis of subclinical hypothyroidism must be considered in every patient with depression  . our study has some limitations , which results mainly from its retrospective and naturalistic design . we have no clinical data , data for subtypes of bipolar disorder type i and ii and rapid cycling . diagnostic groups were based on diagnosis at discharge from the hospital , so it might be inaccurate in some cases , where strict diagnostic procedure using clinical criteria was not done . we only have data representing current medical condition and have no information regarding past thyroid disorders and their treatment . we also have no date on detailed thyroid assessment ( t3 , t4 , anti - thyroid autoantibodies , results of ultrasonograph examinations ) . diagnostic groups of our study were not homogenous , there were less women in the schizophrenia group comparing to other groups , while patients with unipolar and bipolar depression were significantly older comparing to other groups . also , the bipolar disorder group was smaller comparing to schizophrenia and unipolar disorder ( this is particularly true for bipolar mania group ) . these factors may affect results of inter- and intra - group comparisons . in case of patients with bipolar disorder lithium may cause hypothyroidism , it was also reported that anti - depressants   as well as haloperidol   may affect thyroid functions and we have no detailed data on treatment that could be included in the analysis . on the other hand , the large sample size and ability to compare three major clinical groups ( schizophrenia , unipolar depression and bipolar disorder ) are strengths of the study .