Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism. Treatment for congenital hypothyroidism: thyroxine alone or thyroxine plus triiodothyronine? Initial treatment dose of L-thyroxine in congenital hypothyroidism. Cognition and behavior at school entry in children with congenital hypothyroidism treated early with high-dose levothyroxine. L-Thyroxine Treatment of Preterm Newborns: Clinical and Endocrine Effects Outcome of Lower L-Thyroxine Dose for Treatment of Congenital Hypothyroidism Growth Follow-up in 100 Children with Congenital Hypothyroidism Before and During Treatment
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
BACKGROUND Congenital hypothyroidism ( CHT ) affects approximately one in 3000 to 4000 infants .
CHT is one of the most common preventable causes of learning difficulties .
Optimal management of CHT requires early diagnosis and prompt treatment to avoid abnormal neurodevelopmental outcome .
One of the main issues in the management of CHT relates to the initial dose of levothyroxine to be used in order to achieve optimal results in terms of intellectual development .
Currently , it remains unclear whether high dose thyroid hormone replacement is more effective than low dose in the treatment of CHT .
Further research is required to determine an appropriate dose that improves mental and psychomotor developmental outcomes .
OBJECTIVES To determine the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism .