hashimoto 's thyroiditis or chronic autoimmune thyroiditis is the most common cause of acquired hypothyroidism or goiter in children over 6 years of age in iodine - sufficient areas of the world . the patients generally are genetically predisposed to the disease and family history of thyroid disorder is seen in up to 3040% of patients [ 1 , 2 ] . this condition is characterized by lymphocytic infiltration and destruction of thyroid parenchyma and high serum concentration of autoantibodies against thyroid tissue . documenting high serum concentrations of anti - thyroid peroxidase ( anti - tpo ) and/or anti - thyroglobulin ( anti - tg ) autoantibodies is sufficient to diagnose chronic autoimmune thyroiditis as the cause of a patient 's hypothyroidism . the prevalence of autoimmune thyroiditis ( defined by characteristic echographic pattern and elevated concentration of anti - tpo and/or anti - tg autoantibodies ) in schoolchildren is approximately 2.5% . the genetic factors which are associated with hashimoto 's thyroiditis lie in the human leukocyte antigen ( hla ) complex , while an association with cytotoxic t - lymphocyte - associated protein 4 ( ctla-4 ) or a closely linked gene has also been described [ 5 , 6 ] . type 1 diabetes mellitus , like autoimmune thyroiditis , is an organ - specific autoimmune disease which is caused by a complex interaction of genetic and environmental factors . it is reported that hla and ctla-4 polymorphism is associated with type 1 diabetes mellitus as well as with autoimmune thyroid disease [ 4 , 5 , 7 ] . most patients with newly diagnosed type 1 diabetes mellitus have elevated concentrations of autoantibodies against langerhans islet -cells . the antigens for these antibodies are insulin ( iaa ) , glutamic acid decarboxylase ( gad ) , insulinoma associated autoantigen 2 ( ia2a ) , and zinc transporter 8 ( znt8a ) . the autoantibodies appear in the blood at as early as 6 months of age and are detectable several years before the clinical manifestation of the disease [ 8 , 9 ] . these antibodies can have both a diagnostic and predictive value for type 1 diabetes mellitus . if the incidence rate continues to increase on the existing path , there is the risk of doubling of global incidence . there is large evidence that autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus is increased by up to 2030% [ 11 , 12 ] . in contrast , little is known about anti - islet cell autoimmune status in patients with autoimmune thyroid disease . therefore we evaluated the concentration of antibodies against glutamic acid decarboxylase ( gad ) which are widely used as a diagnostic and predictive tool for type 1 diabetes mellitus . we studied georgian school - aged children , up to 16 years of age , who had been diagnosed as having chronic autoimmune thyroiditis . enmedic ,  a clinic which has nearly a hundred years of experience in the field of endocrinology and to which patients with endocrine pathology are referred from all regions of georgia . the exclusion criteria for this study were diabetes mellitus , first - degree relatives with type 1 diabetes mellitus , other autoimmune conditions , turner syndrome , and down syndrome . the diagnosis of chronic autoimmune thyroiditis was established by the responsible pediatric endocrinologist , confirmed by elevated levels of serum thyrotropin ( tsh ) and autoantibodies against thyroid peroxidase and/or thyroglobulin . the exclusion criteria for control subjects were first - degree relatives with type 1 diabetes mellitus and a history of thyroid disease . the serum concentrations of anti - tpo and anti - tg antibodies were investigated in the control group and were not elevated , within reference range , in all subjects recruited in this group . glutamic acid decarboxylase antibodies were detected using quantitative elisa ( produced by rsr limited , uk ) . the assay has specificity of 99% and sensitivity of 72% . cut - off value for positive results was established as 5  u / ml . to assess the plasma concentration of anti - tpo and anti - tg antibodies we used the advia centaur xp anti - tpo and anti - tg assays ( produced by siemens ) using chemiluminescent technology . samples were defined as anti - tpo positive when the level was higher than 60  iu / ml and anti - tg positive when the level was higher than 60  iu / ml . we use advia centaur xp tsh assay ( produced by siemens ) for measurement of tsh plasma concentration , and reference range was 044.0  iu / ml , and we use advia centaur xp ft4 assay ( produced by siemens ) for measurement of free thyroxine ( ft4 ) plasma concentration , and reference range was 0.82.0  ng / dl . fisher 's exact probability test was used to assess the significance of differences of gad positivity between the patients with autoimmune thyroiditis and healthy control subjects . the study was approved by the local ethical committee of v. iverieli endocrinology metabology dietology center study number enm-001 , in agreement with helsinki declaration ( 1977 ) regarding ethical standards for clinical studies in medicine . the patient group consisted of 41 children ( 10 males and 31 females ) , aged from 6 to 16 ( mean 13.15 ; median 13.00 ; sd 2.231 ) . as the control group there were 51 healthy subjects ( 17 males and 34 females ) , age from 6 to 16 years ( mean 12.96 ; median 13.00 ; sd 2.441 ) . in the study group 37 of the 41 patients ( 90.2% ) were receiving treatment with levothyroxine , three ( 7.3% ) had primary hypothyroidism ( without goiter ) with tsh elevation ( tsh values were from 11.57 to 137.42  iu / ml ; median : 74.89 ) , six ( 14.6% ) had subclinical hypothyroidism ( without goiter ) ( tsh values were from 5.12 to 7.36  iu / ml ; median : 5.28 ) , five ( 12.2% ) had primary hypothyroidism with diffuse goiter ( tsh values were from 15.24 to 150.01  iu / ml ; median : 37.45 ) , 21 ( 51.2% ) had subclinical hypothyroidism with diffuse goiter ( tsh values were from 4.43 to 6.28  iu / ml ; median : 4.98 ) , four ( 9.8% ) had subclinical hypothyroidism with nodular goiter ( tsh values were from 4.67 to 4.99  iu / ml ; median : 4.88 ) , one had primary hypothyroidism with nodular goiter , and one presented with hyperthyroidism and diffuse goiter ( table 1 ) . of the 41 patients with autoimmune thyroiditis 4 ( 9.8% ) none of the 51 control subjects was positive for gad . in the four gad positive patients three had diffuse goiter and one had nodular goiter , and among them two had primary hypothyroidism and two had subclinical hypothyroidism ( table 2 ) . the frequency of gad positivity in the autoimmune thyroiditis group was significantly higher than in the control subjects ( p = 0.036 ) ( table 3 ) . the assessment of other anti - islet antibodies , antibodies against adrenal glands , and iga tissue transglutaminase antibodies is also planned . glutamic acid decarboxylase of 65  kda ( gad65 ) is one of the major autoantigens for type 1 diabetes mellitus . glutamic acid decarboxylase catalyzes the synthesis of gamma - aminobutyric acid ( gaba ) , which is known as a major inhibitory neurotransmitter in the central nervous system ( cns ) , but it is also present outside the cns . it is also found in -cells of islets of langerhans , but its functional role remains largely unknown . antibodies to glutamic acid decarboxylase serve as a predictor and marker of type 1 diabetes mellitus . the predictive sensibility of gad antibodies for type 1 diabetes mellitus in the general population is approximately 50% . in our study we show that the frequency of gad positivity in the autoimmune thyroiditis group was significantly higher than in the control subjects ( p = 0.036 ) . our findings support the concept that patients with autoimmune thyroid disease may be at high risk of developing type 1 diabetes mellitus , as is concluded by the studies of healthy children from the general population , which show marked increase of incidence of type 1 diabetes mellitus in subjects with positive serum antibodies against pancreatic islet cells [ 15 , 16 ] . according to our findings we concluded that the screening for gad antibodies in patients with autoimmune thyroid disease may reveal the individuals with increased risk of developing type 1 diabetes mellitus ; however , the importance of screening autoantibodies and then follow - up of antibody positive patients remains controversial , as the disease can not be prevented so far . but it is still very important to reveal the different risk groups as recent studies revealed a markedly reduced rate of diabetic ketoacidosis and other complications at onset of type 1 diabetes in individuals screened for islet autoantibodies . in the study we found that the frequency of gad antibody positivity in autoimmune thyroiditis patients was significantly higher ( 9.8% , p = 0.036 ) than in the control group . our findings support the concept that patients with autoimmune thyroid disease may develop type 1 diabetes mellitus in future life . though the onset of type 1 diabetes can not be prevented , it is still very important to reveal the different risk groups as the knowledge of the increased risk can help to prevent acute onset of the disease with ketoacidosis and concomitant morbidities .
aim . chronic autoimmune thyroiditis and type 1 diabetes mellitus are organ - specific autoimmune diseases . 
 there is large evidence that autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus is increased , but little is known about anti - islet cell autoimmune status in patients with chronic autoimmune thyroiditis . 
 we evaluated the concentration of antibodies against glutamic acid decarboxylase ( gad ) which are widely used as a diagnostic and predictive tool for type 1 diabetes mellitus , in school - aged georgian children with chronic autoimmune thyroiditis . 
 methods . 
 the frequency of anti - gad antibodies was measured in georgian school - aged children with chronic autoimmune thyroiditis and compared to healthy age and sex matched controls . 
 results . of the 41 patients with chronic autoimmune thyroiditis 4 ( 9.8% ) were positive for gad antibodies . 
 the frequency of gad positivity in the chronic autoimmune thyroiditis group was significantly higher than in the control subjects ( p = 0.036 ) . conclusion . in the study we found that the frequency of gad antibody positivity in autoimmune thyroiditis patients was significantly higher ( 9.8% , p = 0.036 ) than in the control group . 
 our findings support the concept that patients with autoimmune thyroid disease may develop type 1 diabetes mellitus in future life .