human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To evaluate the influence of initial and postinitial treatment factors on cognitive , psychomotor , and psychological outcome in schoolchildren with congenital hypothyroidism ( CH ) . STUDY DESIGN We studied 45 patients ( 19 with severe CH and 26 with mild CH ) and 37 control children by correlating  initial and postinitial treatment factors ( free thyroxine and thyroid-stimulating hormone [ TSH ] concentrations , and the percentage of overtreatment and undertreatment periods ) with the results of  neuropsychological tests and behavior  ( as reported on the Teacher Report Form [ TRF ] ) . RESULTS The global IQ of the children with CH was comparable to that of the controls ; visuomotor and verbal scores were lower , and total TRF scores were higher . Ethnic group , previous development , and overtreatment predicted IQ and verbal scores , with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated . As initial treatment was less satisfactory , total TRF scores were higher . CONCLUSIONS Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields . Overtreatment may advance cognitive development in 5 - 1/2- to 7-year-olds . Suboptimal initial treatment may lead to behavioral problems . We recommend that TSH concentrations be maintained within the normal range in patients with CH OBJECTIVE To compare the effects of therapy with thyroxine ( T4 ) plus triiodothyronine ( T3 ) versus T4 alone from the first days of life in screened congenital hypothyroid ( CH ) infants . METHODS We examined 14 CH infants diagnosed by neonatal screening and a group of control infants . CH patients were divided r and omly into 2 groups , 1 treated with T4 alone ( group 1 ) and the other treated with T4 plus T3 ( liothyronine ; group 2 ) . In all patients  electrocardiography and thyroid hormone evaluations  were performed before and 15 and 30 days and 3 , 6 , and 12 months after the beginning of therapy . Psychological tests were also performed at 6 and 12 months of age in CH patients and in other matched controls . RESULTS After 15 days of treatment , serum thyrotropin ( TSH ) levels become normal in 5 of 7 cases of group 1 ( median TSH level 10.7 micro U/ml ) and in 1 of 7 cases of group 2 ( median TSH level 72.5 micro U/ml ) . At the same period , serum-free thyroid hormone levels were within the normal range in both groups , but free T4 values were significantly higher in group 1 than in group 2 and in controls . At the subsequent examinations , free T4 values were within the upper normal limit in group 1 , whereas they remained within the normal range in group 2 . No clinical or electrocardiographic signs of heart disease were found in any of the patients . The psychometric quotient in CH infants was significantly lower than in controls , but similar in patients of group 1 and group 2 . CONCLUSIONS The combined treatment with T4 plus T3 seems not to show significant advantages , at least in our experimental conditions , compared with the traditional treatment with T4 alone in early treated CH infants . A further longer and more extensive follow-up is m and atory OBJECTIVES To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism ( CH ) by evaluating the time course of rise of thyroxine ( T(4 ) ) and free T(4 ) concentrations into an established " target range " and normalization of thyroid-stimulating hormone ( TSH ) and to reevaluate the " target range " for T(4 ) and free T(4 ) concentrations during the first 2 weeks of CH treatment . STUDY DESIGN Infants of birth weight 3 to 4 kg with CH ( n = 47 ) detected by newborn screening were r and omly assigned into three L-thyroxine treatment dose arms : 37.5 microg/day ( group 1 ) ; 62.5 microg/day for 3 days , then 37.5 microg/day ( group 2 ) ; and 50 microg/day ( group 3 ) .  Serum T(4 ) , free T(4 ) , triiodothyronine ( T(3 ) ) , free T(3 ) , and TSH were measured before treatment and at 3 days and 1 , 2 , 4 , 8 , and 12 weeks after treatment . RESULTS T(4 ) and free T(4 ) concentrations increased into the target range ( 10 to 16 microg/dL ) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1 ; 50 microg/day ( average 14.5 microg/kg/day ) provided the most rapid normalization of TSH by 2 weeks . With the use of linear regression analysis of T(4 ) versus TSH or free T(4 ) versus TSH plots , the intercept at the lower range of normal for TSH ( 1.7 mU/L ) showed T(4 ) = 19.5 microg/dL and free T(4 ) = 5.23 ng/dL. CONCLUSIONS Initial dosing of 50 microg/day ( 12 - 17 microg/kg per day ) raised serum T(4 ) and free T(4 ) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy . We recommend consideration of a somewhat higher " target range " of 10 to 18 microg/dL for T(4 ) and 2 to 5.0 ng/dL for free T(4 ) during the first 2 weeks of L-thyroxine treatment . After 2 weeks of treatment , the target range drops to 10 to 16 microg/dL for T(4 ) and 1.6 to 2.2 for free T(4 ) OBJECTIVE To document cognition and behavior at school entry in these patients . Study design Eighteen children with congenital hypothyroidism ( CH ; 9 severe and 9 moderate , based on a surface of the knee epiphyses at diagnosisor=0.05 cm(2 ) ) treated from a median of 14 days with a median of 12.0 microg/kg per day of levothyroxine  were evaluated at 5 years , 9 months , with the McCarthy Scale and the Question naire for Evaluation of Social Behavior , as were 40 control children . RESULTS The global IQs at 5 years , 9 months , were similar : medians ( range ) were 102 ( 87 to 133 ) , 102 ( 84 to 135 ) , and 115 ( 88 to 136 ) ( not significant ) for severe CH , moderate CH , and control children , respectively . The behavioral scores of CH children were within the normal range . However , the number of times when plasma TSH was > 6.0 mIU/L during treatment was correlated positively with anxiety ( P=.02 ) and inattention ( P=.05 ) , whereas the number of times TSH was < 0.8 mIU/L was correlated with lower verbal scores ( P=.05 ) . CONCLUSIONS Children with severe CH treated early with a high dose of levothyroxine have normal global development and behavior at school entry Preterm newborns have low serum thyroxine ( T4 ) levels compared with late-gestational fetuses . Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction . We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age < 31 wk . Forty newborns were r and omized in a double blind protocol : 20 infants received a daily dose of 20 μg/kg l-T4 for 2 wk , whereas 20 control infants received saline .  Serum concentrations of T4 , triiodothyronine ( T3 ) , reverse T3 ( rT3 ) , thyroglobulin ( TG ) , and TSH were measured weekly as well as serum levels of GH , prolactin , and IGF-I. After 2 wk , a TSH-releasing hormone ( TRH ) test was performed . Neonatal illness and outcome was evaluated by noting heart rate , oxygen requirement , duration of ventilation , development of chronic lung disease , oral fluid intake , and weight gain ; a Bayley score was done at the corrected age of 7 mo . l-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels , whereas the postnatal decline in serum rT3 was more gradual . l-T4 treatment was associated with a decrease in serum TG and TSH levels . TRH injection induced a definite rise in serum TSH and T3 in controls , but not in L-T4 treated newborns . Neither l-T4 treatment , nor TRH administration appeared to alter circulating levels of prolactin , GH , or IGF-I. In contrast to the pronounced endocrine effects , no clinical effects of l-T4 administration were detected The appropriateness of the recommended L-thyroxine dose ( 10 - 15 μg/kg/day ) for the treatment of congenital hypothyroidism has been question ed because of the risk of iatrogenic hyperthyroidism . We report the outcome of 23 newborns with congenital primary hypothyroidism treated with 25 μg L-thyroxine per day ( 5.3 - 9.2 μg/kg/day ) and followed for an average of 59 months . Serum thyroxine ( T4 ) values increased ( X = 11.4 ± 2.7 μg/dL ) within 4 weeks posttherapy ; eight infants had T4 levels ≥13 μg/dL on only half the currently recommended dose . Thyroid-stimulating hormone ( TSH ) values remained elevated in 18 of 21 patients for 2 - 21 months despite a high-normal T4 . Psychometric tests were performed in 19 of the 23 patients . The mean Full Scale IQ for the congenital hypothyroid group ( n = 16 ) was 101.4 ± 13.2 with comparable Verbal and Performance IQ scores . Patients with a bone age ( BA ) of ≤32 weeks or T4 < 2 μg/dL at initial evaluation had significantly Lower Verbal IQ scores . A st and ardized parent-report assessment of behavioral and emotional functioning revealed subgroup scale scores that were indistinguishable from non clinical norms . We conclude that ( 1 ) average range IQ scores and positive behavioral adaptation are observed in congenitally hypothyroid children treated with L-thyroxine doses lower than currently recommended ; ( 2 ) the L-thyroxine dose should be individualized to prevent iatrogenic hyperthyroidism ; ( 3 ) TSH normalization should not be a primary objective of treatment , and ( 4 ) a prospect i ve study comparing the advantages and risks of different doses of L-thyroxine is needed In order to assess the influence of age at onset of treatment on subsequent growth , height , weight , head circumference ( HC ) and bone age as estimated by Greulich-Pyle and TW2-RUS methods , 100 children with congenital hypothyroidism ( CH ) were studied before and during adequate treatment up to 5 years of age . The patients were divided into five groups according to age at the start of treatment : Group 1 : < 2 months ( n = 26 ) ; Group 2 : 2 - 3 months ( n = 13 ) ; Group 3 : 3 - 6 months ( n = 21 ) ; Group 4 : 6 - 12 months ( n = 20 ) ; Group 5 : 12 - 24 months ( n = 20 ) . Before treatment , groups 1 and 2 differed significantly from the others in height ( p < 0.001 ) . With hormone therapy , catch-up growth was observed in groups 3 to 5 , but at age 5 years no differences were found between groups . In all groups , height at 5 years of age correlated significantly with children 's midparental height ( p < 0.002 ) . Bone age was initially retarded in groups 3 to 5 , but approximated the chronological age by age 5 years . Initially , HC was less affected than height and remained relatively larger up to age 5 years in all groups . These findings show that thyroid hormone replacement in CH as late as 24 months corrects the short stature and delayed bone age by age 5 years 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To evaluate the influence of initial and postinitial treatment factors on cognitive , psychomotor , and psychological outcome in schoolchildren with congenital hypothyroidism ( CH ) . STUDY DESIGN We studied 45 patients ( 19 with severe CH and 26 with mild CH ) and 37 control children by correlating  initial and postinitial treatment factors ( free thyroxine and thyroid-stimulating hormone [ TSH ] concentrations , and the percentage of overtreatment and undertreatment periods ) with the results of  neuropsychological tests and behavior  ( as reported on the Teacher Report Form [ TRF ] ) . RESULTS The global IQ of the children with CH was comparable to that of the controls ; visuomotor and verbal scores were lower , and total TRF scores were higher . Ethnic group , previous development , and overtreatment predicted IQ and verbal scores , with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated . As initial treatment was less satisfactory , total TRF scores were higher . CONCLUSIONS Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields . Overtreatment may advance cognitive development in 5 - 1/2- to 7-year-olds . Suboptimal initial treatment may lead to behavioral problems . We recommend that TSH concentrations be maintained within the normal range in patients with CH OBJECTIVE To compare the effects of therapy with thyroxine ( T4 ) plus triiodothyronine ( T3 ) versus T4 alone from the first days of life in screened congenital hypothyroid ( CH ) infants . METHODS We examined 14 CH infants diagnosed by neonatal screening and a group of control infants . CH patients were divided r and omly into 2 groups , 1 treated with T4 alone ( group 1 ) and the other treated with T4 plus T3 ( liothyronine ; group 2 ) . In all patients  electrocardiography and thyroid hormone evaluations  were performed before and 15 and 30 days and 3 , 6 , and 12 months after the beginning of therapy . Psychological tests were also performed at 6 and 12 months of age in CH patients and in other matched controls . RESULTS After 15 days of treatment , serum thyrotropin ( TSH ) levels become normal in 5 of 7 cases of group 1 ( median TSH level 10.7 micro U/ml ) and in 1 of 7 cases of group 2 ( median TSH level 72.5 micro U/ml ) . At the same period , serum-free thyroid hormone levels were within the normal range in both groups , but free T4 values were significantly higher in group 1 than in group 2 and in controls . At the subsequent examinations , free T4 values were within the upper normal limit in group 1 , whereas they remained within the normal range in group 2 . No clinical or electrocardiographic signs of heart disease were found in any of the patients . The psychometric quotient in CH infants was significantly lower than in controls , but similar in patients of group 1 and group 2 . CONCLUSIONS The combined treatment with T4 plus T3 seems not to show significant advantages , at least in our experimental conditions , compared with the traditional treatment with T4 alone in early treated CH infants . A further longer and more extensive follow-up is m and atory OBJECTIVES To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism ( CH ) by evaluating the time course of rise of thyroxine ( T(4 ) ) and free T(4 ) concentrations into an established " target range " and normalization of thyroid-stimulating hormone ( TSH ) and to reevaluate the " target range " for T(4 ) and free T(4 ) concentrations during the first 2 weeks of CH treatment . STUDY DESIGN Infants of birth weight 3 to 4 kg with CH ( n = 47 ) detected by newborn screening were r and omly assigned into three L-thyroxine treatment dose arms : 37.5 microg/day ( group 1 ) ; 62.5 microg/day for 3 days , then 37.5 microg/day ( group 2 ) ; and 50 microg/day ( group 3 ) .  Serum T(4 ) , free T(4 ) , triiodothyronine ( T(3 ) ) , free T(3 ) , and TSH were measured before treatment and at 3 days and 1 , 2 , 4 , 8 , and 12 weeks after treatment . RESULTS T(4 ) and free T(4 ) concentrations increased into the target range ( 10 to 16 microg/dL ) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1 ; 50 microg/day ( average 14.5 microg/kg/day ) provided the most rapid normalization of TSH by 2 weeks . With the use of linear regression analysis of T(4 ) versus TSH or free T(4 ) versus TSH plots , the intercept at the lower range of normal for TSH ( 1.7 mU/L ) showed T(4 ) = 19.5 microg/dL and free T(4 ) = 5.23 ng/dL. CONCLUSIONS Initial dosing of 50 microg/day ( 12 - 17 microg/kg per day ) raised serum T(4 ) and free T(4 ) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy . We recommend consideration of a somewhat higher " target range " of 10 to 18 microg/dL for T(4 ) and 2 to 5.0 ng/dL for free T(4 ) during the first 2 weeks of L-thyroxine treatment . After 2 weeks of treatment , the target range drops to 10 to 16 microg/dL for T(4 ) and 1.6 to 2.2 for free T(4 ) OBJECTIVE To document cognition and behavior at school entry in these patients . Study design Eighteen children with congenital hypothyroidism ( CH ; 9 severe and 9 moderate , based on a surface of the knee epiphyses at diagnosisor=0.05 cm(2 ) ) treated from a median of 14 days with a median of 12.0 microg/kg per day of levothyroxine  were evaluated at 5 years , 9 months , with the McCarthy Scale and the Question naire for Evaluation of Social Behavior , as were 40 control children . RESULTS The global IQs at 5 years , 9 months , were similar : medians ( range ) were 102 ( 87 to 133 ) , 102 ( 84 to 135 ) , and 115 ( 88 to 136 ) ( not significant ) for severe CH , moderate CH , and control children , respectively . The behavioral scores of CH children were within the normal range . However , the number of times when plasma TSH was > 6.0 mIU/L during treatment was correlated positively with anxiety ( P=.02 ) and inattention ( P=.05 ) , whereas the number of times TSH was < 0.8 mIU/L was correlated with lower verbal scores ( P=.05 ) . CONCLUSIONS Children with severe CH treated early with a high dose of levothyroxine have normal global development and behavior at school entry Preterm newborns have low serum thyroxine ( T4 ) levels compared with late-gestational fetuses . Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction . We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age < 31 wk . Forty newborns were r and omized in a double blind protocol : 20 infants received a daily dose of 20 μg/kg l-T4 for 2 wk , whereas 20 control infants received saline .  Serum concentrations of T4 , triiodothyronine ( T3 ) , reverse T3 ( rT3 ) , thyroglobulin ( TG ) , and TSH were measured weekly as well as serum levels of GH , prolactin , and IGF-I. After 2 wk , a TSH-releasing hormone ( TRH ) test was performed . Neonatal illness and outcome was evaluated by noting heart rate , oxygen requirement , duration of ventilation , development of chronic lung disease , oral fluid intake , and weight gain ; a Bayley score was done at the corrected age of 7 mo . l-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels , whereas the postnatal decline in serum rT3 was more gradual . l-T4 treatment was associated with a decrease in serum TG and TSH levels . TRH injection induced a definite rise in serum TSH and T3 in controls , but not in L-T4 treated newborns . Neither l-T4 treatment , nor TRH administration appeared to alter circulating levels of prolactin , GH , or IGF-I. In contrast to the pronounced endocrine effects , no clinical effects of l-T4 administration were detected The appropriateness of the recommended L-thyroxine dose ( 10 - 15 μg/kg/day ) for the treatment of congenital hypothyroidism has been question ed because of the risk of iatrogenic hyperthyroidism . We report the outcome of 23 newborns with congenital primary hypothyroidism treated with 25 μg L-thyroxine per day ( 5.3 - 9.2 μg/kg/day ) and followed for an average of 59 months . Serum thyroxine ( T4 ) values increased ( X = 11.4 ± 2.7 μg/dL ) within 4 weeks posttherapy ; eight infants had T4 levels ≥13 μg/dL on only half the currently recommended dose . Thyroid-stimulating hormone ( TSH ) values remained elevated in 18 of 21 patients for 2 - 21 months despite a high-normal T4 . Psychometric tests were performed in 19 of the 23 patients . The mean Full Scale IQ for the congenital hypothyroid group ( n = 16 ) was 101.4 ± 13.2 with comparable Verbal and Performance IQ scores . Patients with a bone age ( BA ) of ≤32 weeks or T4 < 2 μg/dL at initial evaluation had significantly Lower Verbal IQ scores . A st and ardized parent-report assessment of behavioral and emotional functioning revealed subgroup scale scores that were indistinguishable from non clinical norms . We conclude that ( 1 ) average range IQ scores and positive behavioral adaptation are observed in congenitally hypothyroid children treated with L-thyroxine doses lower than currently recommended ; ( 2 ) the L-thyroxine dose should be individualized to prevent iatrogenic hyperthyroidism ; ( 3 ) TSH normalization should not be a primary objective of treatment , and ( 4 ) a prospect i ve study comparing the advantages and risks of different doses of L-thyroxine is needed In order to assess the influence of age at onset of treatment on subsequent growth , height , weight , head circumference ( HC ) and bone age as estimated by Greulich-Pyle and TW2-RUS methods , 100 children with congenital hypothyroidism ( CH ) were studied before and during adequate treatment up to 5 years of age . The patients were divided into five groups according to age at the start of treatment : Group 1 : < 2 months ( n = 26 ) ; Group 2 : 2 - 3 months ( n = 13 ) ; Group 3 : 3 - 6 months ( n = 21 ) ; Group 4 : 6 - 12 months ( n = 20 ) ; Group 5 : 12 - 24 months ( n = 20 ) . Before treatment , groups 1 and 2 differed significantly from the others in height ( p < 0.001 ) . With hormone therapy , catch-up growth was observed in groups 3 to 5 , but at age 5 years no differences were found between groups . In all groups , height at 5 years of age correlated significantly with children 's midparental height ( p < 0.002 ) . Bone age was initially retarded in groups 3 to 5 , but approximated the chronological age by age 5 years . Initially , HC was less affected than height and remained relatively larger up to age 5 years in all groups . These findings show that thyroid hormone replacement in CH as late as 24 months corrects the short stature and delayed bone age by age 5 years 
    Output:
    