congenital hypothyroidism in neonates and very young infants is usually caused by thyroid 
 dysgenesis associated with an absent , ectopic , or hypoplastic thyroid gland , and can be 
 detected by neonatal screening in the general population .
although this illness itself is 
 considered to be unchanged throughout the patient s life , it can be transient in certain 
 cases , for example , infants of mothers with chronic autoimmune thyroiditis ( 1 ) .
hypothyroidism in young children is mostly caused by chronic autoimmune thyroiditis , but it 
 is quite rare before the age of 3 ( 2 ) .
thomas 
 et al . described four children , nine months to two years of age at the 
 time of diagnosis , who had hypothyroidism that was most likely to have been caused by 
 chronic autoimmune thyroiditis ( 3 ) .
trab , such as tsh - binding 
 inhibitor immunoglobulin ( tbii ) and thyroid stimulating antibody ( tsab ) , have been detected 
 in most patients with hyperthyroidism due to graves disease .
this patient trab 
 changed from a blocking type to a stimulating type in association with the development of 
 hyperthyroidism ( 4 ) . in this report
, we describe a first case with hyperthyroidism , who was diagnosed with ch at 
 neonatal screening and since then had been treated for 13 yr with thyroid hormone .
his mother was healthy , and his father had a 
 clinical history of hyperthyroidism , which was treated with antithyroid drugs for one year 
 when he was 42 .
the patient s birth weight was 2770 g , and his gestational age was 40 wk . at 
 the age of 16 d
, he was referred to our hospital because of positive results at neonatal 
 screening for ch .
the dried blood tsh at the ages of 5 and 12 d were 76.76 
 u / ml and 38.08 u / ml , respectively .
at the age of 16 d , 
 the serum levels of tsh , t4 and t3 were 91.0 u / ml 
 ( adult normal range : 0.45.0 ) , 6.9 g / dl ( adult normal range : 3.712.1 ) and 
 1.36 ng / ml ( adult normal range : 0.71.8 ) , respectively .
the size of the right distal femoral epiphysis was 6  3 mm and that 
 of the left was 6.5  4 mm on x - ray examination .
he was diagnosed with subclinical 
 congenital hypothyroidism and received hormone replacement therapy from the age of 34 d. the 
 initial dose was 15 mg of desiccated thyroid a day . at the age of 55 d ,
the patient s serum 
 level of tsh was 38.5 u / ml and serum level of free t4 was 0.94 
 ng / ml ( adult normal range : 0.782.12 ) . at the age of 18 mo ,
the scan demonstrated a thyroid gland normally 
 located with homogeneous uptake of radioactive iodine ; the uptake rate was 15% ( normal 
 range , 1040% ) at 24 h. the potassium thiocyanate discharge test showed 25% , and a defect in 
 iodine organification was suspected .
his growth spurt started at about the age of 13 and his adolescence was of the 
 slightly delayed type . ) . at the age of 3 , both the serum level of anti - microsome antibody and 
 anti - thyroglobulin antibody were negative . at the age of 6 ,
the medication was changed to 
 l - thyroxine from desiccated thyroid . at the age of 8 ,
the patient s iq score on wisc - r 
 intelligence test was 133 ( normal 105.4  20.7 ) , and his evaluated bone age was delayed one 
 year compared with his chronological age .
the dosage of l - thyroxine was gradually increased 
 as he grew and the maximum dose was 110 g / day at the age of 11 ( fig .
the dosage of thyroid hormone was gradually 
 increased as he grew and the maximum dose was 110 g / day .
at the age of 13 yr and 4 mo , the serum 
 level of tsh dropped to an undetectable level . ) . until the age of 13 ,
however , at the age of 13 yr and 4 mo , his serum level of tsh dropped to an 
 undetectable level .
the dosage of l - thyroxine was tapered off and eventually eliminated at 
 the age of 14 .
the patient s height and weight were almost the mean until the age of 
 11 .
his growth spurt started at about the age of 13 and his adolescence was of the 
 slightly delayed type .  
the dosage of thyroid hormone was gradually 
 increased as he grew and the maximum dose was 110 g / day .
at the age of 13 yr and 4 mo , the serum 
 level of tsh dropped to an undetectable level .
physical findings at the age of 14 were as follows : height , 165.1 cm ; weight , 50.2 kg ; 
 blood pressure , 124/63 mmhg ; pulse rate , 109 beats / min .
blood examination revealed the following data : free t4 , 4.22 ng / dl ( 0.821.63 ) ; 
 free t3 , 12.0 pg / ml ( 2.04.9 ) ; tsh , less than 0.03 u / ml 
 ( 0.414.01 ) ; trab , 62.5% ; anti - microsome antibody ,  25600 ; anti - thyroglobulin antibody , 
 negative .
a thyroid scan demonstrated a diffuse goiter with homogeneous uptake of radioactive iodine ; 
 the uptake rate was 60% at 24 h. having confirmed hyperthyroidism , therapy was started with antithyroid drugs ( fig .
one month after the start of therapy , the serum level of free t4 
 was normalized .
after two months of therapy , the serum level of tsh had risen to a 
 detectable level . ) .
one month after that , the 
 patient s serum level of free t4 was normalized , and the dosage of mmi was 
 tapered .
two months after the therapy , the patient s serum level of tsh had risen to a 
 detectable level ; however trab was still high , and the dosage of mmi was tapered again and 
 l - thyroxine therapy was added .  
one month after the start of therapy , the serum level of free t4 
 was normalized .
after two months of therapy , the serum level of tsh had risen to a 
 detectable level .
the patient s height and weight were almost the mean until the age of 11 . at annual x - ray 
 examinations ,
bone ages were delayed only one year as compared with his chronological age , 
 and the patient s growth spurt started at about the age of 13 .
his adolescence was of the 
 slightly delayed type . at the age of 15 ,
his height was 167 cm , and his weight was 57 kg 
 ( fig .
the mental development of children with ch has been improved as a result of early detection 
 by neonatal screening and an appropriate therapy ( 5 , 
 6 ) .
newborns classified false positive at ch 
 screening have a very high risk of subclinical hypothyroidism in infancy and early childhood 
 ( 7 ) . nevertheless , it is difficult to decide whether 
 a case should be treated or not in cases such as transient hypothyroidism , transient 
 hyperthyrotropinemia , mild congenital hypothyroidism , and persistent hyperthyrotropinemia at 
 the early phase of consultation ( 8) .
the present case was considered subclinical ch with high tsh and normal t4 
 levels .
thus thyroid hormone replacement therapy was started at the age of 34 d. the 
 patient s serum levels of tsh were sometimes high , and as he grew , the dosage of thyroid 
 hormone was escalated to a maximum dose of 110 g / day until the age of 11 . 

his clinical course was consistent with that of permanent ch till the age of 13 , and it is 
 speculated that he suffered from an iodine organification defect at that time .
van der gaag et al . found transplacental passage of maternal 
 immunoglobulins may play a part in the pathogenesis of ch ( 9 ) .
kato et al . described two cases of ch detected by screening 
 whose sera contained high levels of antibodies in early childhood , and concluded that the 
 antibodies were not derived from maternal immunoglobulins but produced on their own ( 10 ) .
therefore we hypothesize that in the present case hypothyroidism was transient due to 
 immaturity of iodine organification in the thyroid gland as nose et al . 

described previously ( 11 ) , and that afterwards 
 hyperthyroidism developed due to an autoimmune disease , and was diagnosed with the results 
 of serum trab and the thyroid scan .
it is also possible that the patient had several clones 
 of antibodies against thyroid from his early infancy .
although the patient s mother had no 
 thyroid disease and his antibodies were negative in early childhood , a clonal change in his 
 antibodies might have happened and their binding properties could have been altered from the 
 blocking type to the stimulating type ( 4 , 12 ) .
further analysis of thyroid function is 
 apparently necessary to assign the immunological basis of this case and additional follow - up 
 data should be accumulated during the treatment course of this patient .
 we encountered a case with hyperthyroidism at the age of 14 who had been 
 diagnosed with congenital hypothyroidism ( ch ) and had received thyroid hormone replacement 
 therapy . at the age of 16 d , 
 the patient was referred to our hospital because of positive 
 results at neonatal screening for ch . 
 serum level of tsh was 91.0 u / ml 
 and serum level of t4 was 6.9 g / dl . 
 the patient was diagnosed as having 
 hypothyroidism , and hormone replacement therapy was started . 
 thereafter the dosage of 
 thyroid hormone was adjusted and increased gradually as he grew to a maximum dose of 110 
 g / day at the age of 11 . until the age of 13 , the patient s serum 
 levels of tsh were within the normal range ; then , at the age of 13 yr and 4 mo , his serum 
 level of tsh dropped to a level below the detectable range . 
 the dosage of administered 
 thyroid hormone was tapered off and eventually eliminated at the age of 14 . a thyroid scan 
 and a radioactive iodine uptake test demonstrated a diffuse goiter with homogeneous uptake 
 of radioactive iodine ; the uptake rate was 60% at 24 h , and the serum level of tsh 
 receptor antibody ( trab ) was 62.5% at that time . 
 administration of an antithyroid drug was 
 started after confirmation that our patient had developed hyperthyroidism . 
 there have been 
 no case reports similar to our case . 
Introduction
Case Report
Discussion