hypothyroidism and thyroid autoimmunity are commonly associated with aa.aa cases should be screened for thyroid dysfunction and thyroid autoimmunity even in the absence of clinical manifestations suggestive of these diseases . aa cases should be screened for thyroid dysfunction and thyroid autoimmunity even in the absence of clinical manifestations suggestive of these diseases . alopecia areata is a common form of localized , non - scarring hair loss that occurs on any hair bearing skin . it is suspected to be an autoimmune disease , having a genetic predisposition and being influenced by environmental and ethnic factors . the autoimmune process appears to be t - cell mediated although antibodies to anagen phase hair follicle structures are seen in about 90% of patients . this autoimmune etiology has been proposed also on the basis of its association with various autoimmune diseases , including thyroid disorders , vitiligo , pernicious anemia , diabetes mellitus , lupus erythematosus , myasthenia gravis , lichen planus , atopic dermatitis , autoimmune polyendocrine syndrome type i and celiac disease . . thyroid disorders that may be associated with aa include hypothyroidism , hashimoto 's thyroiditis , graves disease and simple goiter . among these , the aim of this work was to determine whether aa is associated with thyroid autoimmunity or thyroid function abnormalities in egyptian patients . this study is a case - control study . it included 50 patients with aa without clinical evidence of thyroid disease ( group a ) that were selected randomly from dermatology outpatient clinic , menoufiya university hospital , menoufiya governorate , egypt during the period from june 2009 to february 2010 . fifty age and sex - matched healthy volunteers ( group b ) were selected as a control group . all patients were subjected to : 
 thorough history taking regarding : 
 onset , course and duration of aapast and family history of aa 
 dermatological examination with determination of site and number of lesionspatients with any autoimmune disorders were excluded.the severity of alopecia areata was graded according to kavak et al . , into : 
 mild : the presence of three or less patches of alopecia with a widest diameter of 3 cm or less , or the disease is limited to the eyelashes and eyebrows.moderate : existence of more than three patches of alopecia , or a patch greater than 3 cm at the widest diameter without alopecia totalis or alopecia universalis.severe : alopecia totalis or alopecia universalis.snake shaped plaques extending to the scalp border or loss of hair in the shape of a wave at the circumference of head defined as ophiasis . patients and controls were subjected to the following : 
 asking about symptoms of hyperthyroidism ( anxiety , insomnia , weight loss , increased appetite , excessive sweating , heat intolerance , bowel and menstural changes , and eye changes as buffiness and double vision ) and symptoms of hypothyroidism ( easy fatigability , slow movement , weight gain , loss of appetite , skin dryness , cold intolerance , hoarseness of voice , and constipation).thorough eye examination ( to detect staring look , exophthalmos , lid lag and external ocular movements ) and thyroid examination ( for size , consistency and pulsations).blood sampling : a sample of 10 ml of venous blood was put into plain tube , left to stand for 10 mins , then centrifuged at 4000 rpm for 5 mins , and then the serum was used for determination of free t3 , free t4 , tsh , tg - ab and tpo-ab.free t3 and free t4 were measured by immulite 2000 which is a solid phase , enzyme labeled chemiluminescent competitive immunoassay . the solid phase is coated with monoclonal murine anti t3 antibody and monoclonal murine anti t4 antibody respectively . the liquid phase consists of alkaline phosphatase conjugated to t3 and to t4 respectively.tsh was measured by immulite 2000 which is a solid phase , two - site chemiluminescent immunometric assay.tg-ab and tpo - ab were detected by enzyme linked immunosorbent assay , which is performed as a solid phase immunoassay . all patients were subjected to : 
 thorough history taking regarding : 
 onset , course and duration of aapast and family history of aa 
 dermatological examination with determination of site and number of lesionspatients with any autoimmune disorders were excluded.the severity of alopecia areata was graded according to kavak et al . , into : 
 mild : the presence of three or less patches of alopecia with a widest diameter of 3 cm or less , or the disease is limited to the eyelashes and eyebrows.moderate : existence of more than three patches of alopecia , or a patch greater than 3 cm at the widest diameter without alopecia totalis or alopecia universalis.severe : alopecia totalis or alopecia universalis.snake shaped plaques extending to the scalp border or loss of hair in the shape of a wave at the circumference of head defined as ophiasis . thorough history taking regarding : 
 onset , course and duration of aapast and family history of aa 
  onset , course and duration of aa past and family history of aa dermatological examination with determination of site and number of lesions patients with any autoimmune disorders were excluded . the severity of alopecia areata was graded according to kavak et al . , into : 
 mild : the presence of three or less patches of alopecia with a widest diameter of 3 cm or less , or the disease is limited to the eyelashes and eyebrows.moderate : existence of more than three patches of alopecia , or a patch greater than 3 cm at the widest diameter without alopecia totalis or alopecia universalis.severe : alopecia totalis or alopecia universalis.snake shaped plaques extending to the scalp border or loss of hair in the shape of a wave at the circumference of head defined as ophiasis . mild : the presence of three or less patches of alopecia with a widest diameter of 3 cm or less , or the disease is limited to the eyelashes and eyebrows . moderate : existence of more than three patches of alopecia , or a patch greater than 3 cm at the widest diameter without alopecia totalis or alopecia universalis . snake shaped plaques extending to the scalp border or loss of hair in the shape of a wave at the circumference of head defined as ophiasis . patients and controls were subjected to the following : 
 asking about symptoms of hyperthyroidism ( anxiety , insomnia , weight loss , increased appetite , excessive sweating , heat intolerance , bowel and menstural changes , and eye changes as buffiness and double vision ) and symptoms of hypothyroidism ( easy fatigability , slow movement , weight gain , loss of appetite , skin dryness , cold intolerance , hoarseness of voice , and constipation).thorough eye examination ( to detect staring look , exophthalmos , lid lag and external ocular movements ) and thyroid examination ( for size , consistency and pulsations).blood sampling : a sample of 10 ml of venous blood was put into plain tube , left to stand for 10 mins , then centrifuged at 4000 rpm for 5 mins , and then the serum was used for determination of free t3 , free t4 , tsh , tg - ab and tpo-ab.free t3 and free t4 were measured by immulite 2000 which is a solid phase , enzyme labeled chemiluminescent competitive immunoassay . the solid phase is coated with monoclonal murine anti t3 antibody and monoclonal murine anti t4 antibody respectively . the liquid phase consists of alkaline phosphatase conjugated to t3 and to t4 respectively.tsh was measured by immulite 2000 which is a solid phase , two - site chemiluminescent immunometric assay.tg-ab and tpo - ab were detected by enzyme linked immunosorbent assay , which is performed as a solid phase immunoassay . asking about symptoms of hyperthyroidism ( anxiety , insomnia , weight loss , increased appetite , excessive sweating , heat intolerance , bowel and menstural changes , and eye changes as buffiness and double vision ) and symptoms of hypothyroidism ( easy fatigability , slow movement , weight gain , loss of appetite , skin dryness , cold intolerance , hoarseness of voice , and constipation ) . thorough eye examination ( to detect staring look , exophthalmos , lid lag and external ocular movements ) and thyroid examination ( for size , consistency and pulsations ) . blood sampling : a sample of 10 ml of venous blood was put into plain tube , left to stand for 10 mins , then centrifuged at 4000 rpm for 5 mins , and then the serum was used for determination of free t3 , free t4 , tsh , tg - ab and tpo - ab . free t3 and free t4 were measured by immulite 2000 which is a solid phase , enzyme labeled chemiluminescent competitive immunoassay . the solid phase is coated with monoclonal murine anti t3 antibody and monoclonal murine anti t4 antibody respectively . tsh was measured by immulite 2000 which is a solid phase , two - site chemiluminescent immunometric assay . tg - ab and tpo - ab were detected by enzyme linked immunosorbent assay , which is performed as a solid phase immunoassay . results were collected , tabulated , and statistically analyzed by ibm personal computer and statistical package spss version 11 . data were statistically described in terms of range , mean  standard deviation ( sd ) , frequencies ( number of cases ) and relative frequencies ( percentages ) when appropriate . student 's t - test was used for comparison between two groups having quantitative variables . kruskal - wallis test was used for comparison between three or more groups not normally distributed having quantitative variables . chi - square test ( 2 ) was used to study association between two or more variables . sperman correlation coefficient ( r ) was used to detect association between qualitative and quantitative variables . results were collected , tabulated , and statistically analyzed by ibm personal computer and statistical package spss version 11 . data were statistically described in terms of range , mean  standard deviation ( sd ) , frequencies ( number of cases ) and relative frequencies ( percentages ) when appropriate . student 's t - test was used for comparison between two groups having quantitative variables . kruskal - wallis test was used for comparison between three or more groups not normally distributed having quantitative variables . chi - square test ( 2 ) was used to study association between two or more variables . sperman correlation coefficient ( r ) was used to detect association between qualitative and quantitative variables . it included 100 subjects divided into two main groups : it included 50 subjects with aa , 37 males and 13 females with age ranging from 6 - 50 years and with a mean  sd age of of 26.38  10.85 years . this group was subdivided according to the severity of aa into three subgroups : group a1 ( mild ) : it included 30 subjects , 21 males ( 42% ) and 9 ( 18% ) females with mean  sd age of 26.76  11.55 years . group a2 ( moderate ) : it included 10 subjects , 9 males ( 18% ) and 1 female ( 2% ) , with mean  sd age of 25.50  8.05 years . group a3 ( severe ) : it included 10 subjects , 7 males ( 14% ) and 3 females ( 6% ) , with mean  sd age of 26.10  12.03 years . clinical data of studied patients it included 50 age and sex - matched healthy control subjects , 35 males and 15 females , with age ranging from 6 - 50 years and with a mean  sd age of of 25.85  11.60 years . no evidence of thyroid disease was detected during local and general examination of patients and controls . among studied patients , six cases of them ( 12% ) were with severe aa and two cases ( 4% ) were with moderate aa [ table 2 ] . comparison of tsh , free t3 and free t4 among studied aa subgroups there were statistically significant differences between cases and controls regarding levels of tsh ( p < 0.05 ) , free t3 ( p < 0.05 ) and free t4 ( p < 0.001 ) [ table 3 ] . statistical comparison between cases and control groups regarding tsh , free t3 , free t4 , tg - ab and tpo - ab tg - ab were positive in 23 ( 46% ) cases . of these , eight cases were with subclinical hypothyroidism and the remaining 15 cases were euthyroid ( data not shown ) . tg - ab were negative in all control subjects with statistically significant difference between cases and controls ( p < 0.001 ) [ table 3 ] . of these , five cases were with subclinical hypothyroidism and the other 19 were euthyroid ( data not shown ) . tpo - ab were negative in all control subjects with statistically significant difference between cases and controls ( p < 0.001 ) [ table 3 ] . there were statistically significant differences among different subgroups of aa regarding tsh ( p < 0.01 ) , free t3 ( p < 0.01 ) and free t4 levels ( p < 0.05 ) [ table 4 ] . statistical comparison between subgroups of alopecia areata regarding tsh , free t3 and free t4 statistically significant differences were found among aa subgroups regarding the levels of both tg - ab ( p < 0.05 ) and tpo - ab ( p < 0.05 ) ) [ table 4 ] . a significant positive correlation was found between tg - ab and the levels of tsh ( p < 0.05 ) , free t3 ( p < 0.01 ) , free t4 ( p < 0.01 ) and tpo - ab ( p < 0.001 ) [ table 5 ] . pearson linear correlation between tg - ab , tpo - ab and other parameters in group ( a ) a significant positive correlation was found between tpo - ab and the levels of tsh ( p < 0.001 ) , free t3 ( p it included 50 subjects with aa , 37 males and 13 females with age ranging from 6 - 50 years and with a mean  sd age of of 26.38  10.85 years . this group was subdivided according to the severity of aa into three subgroups : group a1 ( mild ) : it included 30 subjects , 21 males ( 42% ) and 9 ( 18% ) females with mean  sd age of 26.76  11.55 years . group a2 ( moderate ) : it included 10 subjects , 9 males ( 18% ) and 1 female ( 2% ) , with mean  sd age of 25.50  8.05 years . group a3 ( severe ) : it included 10 subjects , 7 males ( 14% ) and 3 females ( 6% ) , with mean  sd age of 26.10  12.03 years . it included 50 age and sex - matched healthy control subjects , 35 males and 15 females , with age ranging from 6 - 50 years and with a mean  sd age of of 25.85  11.60 years . no evidence of thyroid disease was detected during local and general examination of patients and controls . among studied patients , six cases of them ( 12% ) were with severe aa and two cases ( 4% ) were with moderate aa [ table 2 ] . comparison of tsh , free t3 and free t4 among studied aa subgroups there were statistically significant differences between cases and controls regarding levels of tsh ( p < 0.05 ) , free t3 ( p < 0.05 ) and free t4 ( p < 0.001 ) [ table 3 ] . statistical comparison between cases and control groups regarding tsh , free t3 , free t4 , tg - ab and tpo - ab tg - ab were positive in 23 ( 46% ) cases . of these , eight cases were with subclinical hypothyroidism and the remaining 15 cases were euthyroid ( data not shown ) . tg - ab were negative in all control subjects with statistically significant difference between cases and controls ( p < 0.001 ) [ table 3 ] . of these , five cases were with subclinical hypothyroidism and the other 19 were euthyroid ( data not shown ) . tpo - ab were negative in all control subjects with statistically significant difference between cases and controls ( p < 0.001 ) [ table 3 ] . there were statistically significant differences among different subgroups of aa regarding tsh ( p < 0.01 ) , free t3 ( p < 0.01 ) and free t4 levels ( p < 0.05 ) [ table 4 ] . statistical comparison between subgroups of alopecia areata regarding tsh , free t3 and free t4 statistically significant differences were found among aa subgroups regarding the levels of both tg - ab ( p < 0.05 ) and tpo - ab ( p < 0.05 ) ) [ table 4 ] . a significant positive correlation was found between tg - ab and the levels of tsh ( p < 0.05 ) , free t3 ( p < 0.01 ) , free t4 ( p < 0.01 ) and tpo - ab ( p < 0.001 ) [ table 5 ] . pearson linear correlation between tg - ab , tpo - ab and other parameters in group ( a ) a significant positive correlation was found between tpo - ab and the levels of tsh ( p < 0.001 ) , free t3 ( p alopecia areata is a common cause of non - cicatricial alopecia that occurs in a patchy , confluent or diffuse pattern . it may occur as a single , self - limiting episode or may recur at varying intervals over many years . despite its long history the etiology of aa is not exactly known , however factors such as genetic predisposition , autoimmunity and stress have been suggested . the role of cell mediated immunity was suggested by some investigators due to the lymphocytic infiltrate surrounding the anagen hair follicles and often invading the outer root sheath . hair follicle - specific igg autoantibodies have been found in increased concentrations in the peripheral blood of aa affected individuals compared to kamada et al . , suggested that the immunologic mechanism for the development of aa involves an abnormal accumulation of c3 and sometimes igg and igm in the hair follicles of affected regions , and decreased numbers and disturbed function of t lymphocytes . in all autoimmune diseases , the first and more important is cell - mediated immune responses and the second is antibody - mediated immune responses . in aa and autoimmune thyroid dysfunction , both mechanisms play some role but like many more autoimmune diseases , the primary changes are due to t - cell - mediated immunity . alopecia areata frequently occurs in association with other autoimmune disorders such as generalized vitiligo , lichen planus , morphea , lichen sclerosus et atrophicus , pemphigus foliaceus , atopic dermatitis , hashimoto 's thyroiditis , hypothyroidism , endemic goiter , addison 's disease , pernicious anemia , lupus erythematosus , diabetes mellitus , down 's syndrome and others . the aim of this work was to determine whether aa is associated with thyroid autoimmunity or thyroid function abnormalities in egyptian patients . in the current study , hypothyrodism was found in eight patients ( 16% ) with significant differences between cases and controls regarding levels of tsh , free t3 and free t4 . similarily , kakourou et al . , reported that in evaluation of 157 patients with aa , there were 5% of patients with concomitant aa and thyroid disorder . those have had subclinical hypothyroidism of autoimmune aetiology that was revealed at the time of investigation . our results were also in agreement with a clinical study done by thomas and kadyan who reported that among the thyroid disorders , hypothyroidism was the most frequent form of thyroid function abnormalities associated with aa . also , kasumagi - halilovi detected that thyroid functional abnormalities in the form of hypothyrodism were found in 11.4% of aa patients . thomas and kadyan reported that hypothyroidism was evident in 14.1% of their studied aa population . seyrafi et al . , found thyroid function abnormalities in form of hypothyroidism in 8.9% of the studied aa cases . conversely , puavilai et al . , reported that the prevalence of thyroid disease in patients with aa was relatively low ( 7.2% ) with non - significant difference between patients and controls . although the effects of hypothyroidism on hair have long been known but the mechanism of such effects has not been elucidated . these can be explained by delayed or failure of resumption of anagen hair due to decreased metabolic rate which leads to loss of hair without replacement as well as increased telogen hair counts ( club hair ) before shedding . not all patients with hypothyroidism have alopecia ; thus , it is likely that the magnitude of effect of thyroid hormone on hair growth is variable and its expression may be conditioned by local factors and other hormonal influences . so patients with aa should be screened for thyroid functional abnormalities even in absence of manifestations of hypothyroidism . some investigators recommended the assessment of thyroid gland size and function every six months as this will contribute to the early detection of autoimmune thyroiditis amongst patients with aa , preventing further evolution to severe hypothyroidism . subclinical hypothyroidism is diagnosed when levels of free t3 and free t4 are normal but serum tsh is above the reference range . in this study , there were statistically significant differences among different subgroups of aa regarding tsh , free t3 and free t4 levels . the current study showed that tg - ab were positive in 23 patients ( 46% ) with aa . tg - ab were negative in all control subjects with significant difference between cases and controls . these results were similar to the study done by nanda et al . , who reported a significant increase in serum tg - ab ( 14% ) in children with aa . kurtev and ilev stated that the presence of thyroid autoantibodies in aa patients was 39.5% . they analyzed serum tg - ab level in patients with aa and found it to be elevated in 29.3% of their studied patients . tpo - ab were negative in all control subjects with significant difference between cases and controls . kasumagi - halilovi detected the frequency of thyroid autoantibodies ( tg - ab and tpo - ab ) in aa to be 23.7% that was significantly higher when compared to healthy controls . grandolfo et al . , stated that tg - ab and tpo - ab are found more frequenly in patients with aa than healthy controls . puavilai et al . , reported that there were non - significant differences between patients with aa and control subjects regarding the presence of tg - ab and tpo - ab . tg - ab and tpo - ab were positive in 15 and 19 euthyroid patients respectively . it had been reported that tg - ab and tpo - ab are frequently detectable in euthyroid individuals without functional thyroid abnormalities . prummel and weirsinga concluded that tpo - ab is frequently present in euthyroid subjects , and there is impelling evidence that this constitutes a pre - clinical form of hypothyroidism , although they are also associated with a slightly raised risk for hyperthyroidism . going with that , a number of large - scale studies have established a high prevalence of tpo - ab in normal euthyroid subjects . vanderpump et al . , concluded that the presence of tpo - ab was strongly associated with thyroid failure during 20 years follow up of tpo - ab positive euthyroid individuals . therefore , determination of tpo - ab status seems useful as first triage to select subjects out of a population in whom subsequent tsh testing and follow - up is clinically relevant . these include patients with family history of autoimmune thyroid disorders , patients with other autoimmune disorders and females before and during pregnancy . thyroid dysfunction is more common in women , and is of particular concern in women in reproductive age because abnormal maternal thyroid function during pregnancy has been associated with a wide variety of adverse maternal / fetal outcomes , including increased risk of pre - term birth , miscarriage , fetal death , impaired neuro - psychological development of the child as well as maternal post - partum thyroiditis . taken together , thyroid antibodies are means to identify a certain number of subjects whose thyroid function is completely normal but are at risk of thyroid dysfunction . so it 's of particular importance to follow up euthyroid patients with aa and positive thyroid antibodies . these subjects do not require any treatment but need to be followed up by tsh assay and morphological evaluation of the thyroid gland by ultrasonography to demonstrate an ongoing autoimmune thyroiditis even before modifications of thyroid function . in the current study , there were statistically significant differences among different subgroups of aa regarding the presence of tg - ab and tpo - ab . the significant positive correlation between both tg - ab and tpo - ab and levels of tsh , free t3 and free t4 , detected in the present work , were not previously reported . thomas and kadyan explained the association between aa and thyroid autoimmunity by the formation of organ specific autoantibodies that play a pathogenic role in both disorders . it has been suggested that the antigens in normal hair follicles are normally hidden from recognition by the immune cells . the immune cells need the help of major histocompatibility complex ( mhc ) proteins , which present antigens to immune cells . therefore , in normal hair follicles , where there is normally no or very low , mhc expression , the antigens are ignored . but mhc proteins could be induced in hair follicles by physical trauma and/or the mhc antigens may be  abnormally good  at presenting hair follicle antigens . once the hair follicles express mhc proteins , the immune cells can recognize antigens unique to the hair follicle so they go to work to get rid of them and in doing so , stop hair production . kurtiv and lliev assumed that , the histologic studies have shown cd3+hla - dr+lymphocytic infiltration in the epithelial cells of hair follicles , epidermal keratinocytes , and thyrocytes . these activated t lymphocytes play a role in the pathogenesis of aa and autoimmune thyroid dysfunction , as the aberrant hla - dr antigen statement on the surface of the epithelial cells is realized through hla - dr t lymphocytes . the increased number of activated t lymphocytes in the peripheral blood of patients with aa and autoimmune thyroid dysfunction , points not only to the participation of these lymphocytes in the pathogenesis of these diseases , but also to their inter - relationship . from this work we can support the idea of association between thyroid abnormalities and aa . so , patients with aa should be screened for thyroid functions and thyroid autoimmunity even in absence of clinical manifestations of thyroid dysfunction for early detection of subclinical thyroid abnormalities . these should be followed up for early detection of thyroid dysfunctionthere is significant positive correlation between thyroid antibodies and levels of tsh , free t3 and free t4.levels of tsh are significantly higher , and free t3 and free t4 are significantly lower in severe aa compared with mild and moderate cases.levels of tpo - ab and tg - ab are significantly higher in severe aa compared with mild and moderate cases . these should be followed up for early detection of thyroid dysfunction there is significant positive correlation between thyroid antibodies and levels of tsh , free t3 and free t4 . levels of tsh are significantly higher , and free t3 and free t4 are significantly lower in severe aa compared with mild and moderate cases . levels of tpo - ab and tg - ab are significantly higher in severe aa compared with mild and moderate cases .
context : alopecia areata ( aa ) is a common form of localized , non - scarring hair loss . the etiopathogenesis of the disease is still unclear , but the role of autoimmunity is strongly suggested . 
 aa is commonly associated with various autoimmune disorders ; the most frequent among them is autoimmune thyroid disorders.aim:to determine whether aa is associated with thyroid autoimmunity or thyroid function abnormalities in egyptian patients.materials and methods : fifty subjects with aa ( 37 males and 13 females ) without clinical evidence of thyroid disorders were selected from dermatology outpatient clinic , menoufiya university hospital , menoufiya governorate , egypt , during the period from june 2009 to february 2010 . 
 they were divided into 3 groups according to severity of aa . 
 fifty age and sex - matched healthy volunteers ( 35 males and 15 females ) were selected as a control group . every case and control were subjected to history taking , complete general and dermatological examination . 
 venous blood samples were taken from cases and controls after taking their consents for measurement of thyroid stimulating hormone ( tsh ) , free t3 , freet4 and detection of anti - thyroglobulin antibody ( tg - ab ) and anti - thyroid peroxidase antibody ( tpo - ab).results : subclinical hypothyroidism was detected in 16% of cases . there were statistically significant differences between cases and controls regarding levels of tsh , free t3 and free t4 . 
 there were significant differences between cases and controls regarding the presence of tg - ab and tpo-ab.conclusions:every patient with aa should be screened for thyroid functions and presence of thyroid autoantibodies even in absence of clinical manifestations suggestive of thyroid affection .