Language Disorders in Language Disorders in Children with congenital Children with congenital

hypothyroidismhypothyroidism

Abd El Baky, A,A, Abd El Baky, A,A,

Mammdoh, HM.,Mammdoh, HM.,

Zaky EA,Zaky EA,

Abd El Wahab, MM,Abd El Wahab, MM,Unit of Phoniatrics, Department of Unit of Phoniatrics, Department of Otolaryngology, Otolaryngology, Minia UniversityMinia University..

The thyroid hormones are a major physiological regulator The thyroid hormones are a major physiological regulator

of the brain development. Cell differentiation, migration of the brain development. Cell differentiation, migration

and gene expression are altered as a consequence of the and gene expression are altered as a consequence of the

thyroid hormone deficiency or excess. thyroid hormone deficiency or excess.

Thyroid hormone deficiency when established during the Thyroid hormone deficiency when established during the

critical period of neuronal differentiation produces critical period of neuronal differentiation produces

permanent and severe alteration in the anatomy and permanent and severe alteration in the anatomy and

function of the nervous system (function of the nervous system (cretinismcretinism) ) ((Bernal & Bernal &

Nunez, 1995).Nunez, 1995).

Congenital hypothyroidism Congenital hypothyroidism (CH)(CH) is the deficiency of is the deficiency of

thyroid hormone. Which may be severe and its thyroid hormone. Which may be severe and its

symptoms develop in early weeks of life, in others, symptoms develop in early weeks of life, in others,

lower degree of deficiency occurs, and manifestations lower degree of deficiency occurs, and manifestations

may be delayed for months may be delayed for months (Dessault & Walker, 1993).(Dessault & Walker, 1993).

The prevalence of congenital hypothyroidism is The prevalence of congenital hypothyroidism is

1/40.0001/40.000 infants worldwide infants worldwide ..

Congenital hypothyroidism is Congenital hypothyroidism is twicetwice as common in girls as common in girls

as in boys as in boys (Delange, 1989)(Delange, 1989) . .

Thyroid hormone deficiency does not cause major Thyroid hormone deficiency does not cause major

changes in the gross anatomy of the brain, but it changes in the gross anatomy of the brain, but it

impairs the cytoarchitechture of the neocortex inimpairs the cytoarchitechture of the neocortex in

the cerebellum the cerebellum ( ( Glorieux et al, 1988).Glorieux et al, 1988).

Also, there are changes in the cortical patterns of Also, there are changes in the cortical patterns of

lamination and axonal projection lamination and axonal projection ((Bargagna, 1989).Bargagna, 1989).

Several steps of the brain development seem Several steps of the brain development seem

to be slow down by the deficiency of thyroid to be slow down by the deficiency of thyroid

hormones whereas glial cell formation (gliosis) hormones whereas glial cell formation (gliosis)

and the neuronal cell death are increased. and the neuronal cell death are increased.

T3 regulates the level of neurotrophine to T3 regulates the level of neurotrophine to

promote the development of the cerebral promote the development of the cerebral

cortex cortex (Noven & Arenes, 2006).(Noven & Arenes, 2006).

Magnetic resonance imaging was Magnetic resonance imaging was

reported that most patients with CH reported that most patients with CH

had mild cerebral cortical atrophy in had mild cerebral cortical atrophy in

the frontal and parietal lobes and the frontal and parietal lobes and

identified a delay in myelination in identified a delay in myelination in

patients with untreated congenital patients with untreated congenital

hypothyroidism hypothyroidism (Alves et al., 2004).(Alves et al., 2004).

The neonatal screening programs and early

treatment of CH has been effective in

preventing the serious brain damage and

mental retardation; it is still controversial

whether these patients achieve normal

cognitive skills and language development

or not (Heyerdal et al, 1991).

Also, with early recognition and treatment of CH, with early recognition and treatment of CH,

these children are slower in development than the these children are slower in development than the

normal children. they concluded that congenital normal children. they concluded that congenital

hypothyroidism affect the brain development hypothyroidism affect the brain development

before birth. Some of these effects last after birth before birth. Some of these effects last after birth

even if the replacement therapy is given regularly even if the replacement therapy is given regularly

since birth.since birth.

Glorieux et al, (1988)Glorieux et al, (1988) studied the mental studied the mental

development of the hypothyroid infants and they development of the hypothyroid infants and they

found that there was no difference between the found that there was no difference between the

global quotient in the 12 months. But at age of 18 global quotient in the 12 months. But at age of 18

months and 36 months, the hypothyroid group had months and 36 months, the hypothyroid group had

scientifically lower mean global quotient than the scientifically lower mean global quotient than the

control group. This was mainly in the performance control group. This was mainly in the performance

as well as the in hearing and language aquestion. as well as the in hearing and language aquestion.

Also Also Fuggle et al (1988)Fuggle et al (1988) reported that reported that

congenital hypothyroidism may be associated congenital hypothyroidism may be associated

with hearing and language impairment. with hearing and language impairment.

The problems in receptive language, auditory The problems in receptive language, auditory

processing and reading may persist in processing and reading may persist in

hypothyroid children, particularly if their hypothyroid children, particularly if their

treatment with l-thyroxin is delayed into the treatment with l-thyroxin is delayed into the

third week of life. third week of life.

On psychometric tests, the hypothyroid On psychometric tests, the hypothyroid

group was observed to perform group was observed to perform

scientifically poorer than the normal child scientifically poorer than the normal child

at 3 years of age but seemed to catch up at 3 years of age but seemed to catch up

by age 5 and did not differ on an by age 5 and did not differ on an

expressive language test given at ago of 7 expressive language test given at ago of 7

years years ((Rovet et al,1992Rovet et al,1992).).

Aim Of the workAim Of the work

The objective of this study is to The objective of this study is to

estimate the size of language disorder estimate the size of language disorder

and detect the factors influencing and detect the factors influencing

language acquisition in the children language acquisition in the children

with congenital hypothyrodism. with congenital hypothyrodism.

Subjects and MethodsSubjects and Methods This study included This study included 6060 children. children.

TheThe( ( study groupstudy group)) included included 4040 children who complained from children who complained from

congenital hypothyrodism. This group were collected from el congenital hypothyrodism. This group were collected from el

Minia Insurance Hospital –Pediatric unit. The range of age of Minia Insurance Hospital –Pediatric unit. The range of age of

this group from this group from 3 to 83 to 8 years. years.

The results from the study group were compared to another The results from the study group were compared to another

group group ((control groupcontrol group)), which included , which included 2020 normal children . The normal children . The

range of age of this group from range of age of this group from 3 to 83 to 8 years Children of both years Children of both

groups were matched in the age and sex.groups were matched in the age and sex.

subject

G1G1: the children with congenital : the children with congenital

hypothyroidism with controlled level T3 and hypothyroidism with controlled level T3 and

TSH .TSH .

G2G2: the children with congenital : the children with congenital

hypothyroidism with uncontrolled level T3 and hypothyroidism with uncontrolled level T3 and

TSH.TSH.

G3G3: the children with normal thyroid function.: the children with normal thyroid function.

MethodsMethods

Each child of the 3 groups was Each child of the 3 groups was

subjected to the protocol of language subjected to the protocol of language

assessment, which applied in assessment, which applied in The The

Unit of Phoniatrics-El Minia University Unit of Phoniatrics-El Minia University

Hospitals.Hospitals.

ResultsResults

70 68

71

10

20

30

40

50

60

70

80

90

100

G1 G2 G3

Non-statistical significant difference was obtained between G1 , G2 and G3 as

regard the age (P<0.05).

Age with months

8

14

5

13

119

0

2468

101214161820

G1 G2 G3

male

female

Non-statistical significant difference was obtained between G1 , G2 and G3 as regard sex (P<0.05).

I.QI.Q

7265

82

50

60

70

80

90

100

G1 G2 G3

A statistical significant differences were obtained between

G1 and G2 as regard the I.Q (P>0.05).

A high statistical significant differences were obtained

between G1 and G3 as regard the I.Q (P>0.05).

Mental ageMental age

62

43

75

20

30

40

50

60

70

80

90

100

G1 G2 G3

A statistical significant differences were obtained between G1

and G2 as regard the mental age (P>0.05).

A high statistical significant differences were obtained

between G1 and G3 as regard the mental age (P>0.05).

Age with months

Social ageSocial age

58

38

70

20

30

40

50

60

70

80

90

100

G1 G2 G3

A statistical significant differences were obtained between G1 and G2 as regard the social age (P>0.05).

A high statistical significant differences were obtained between G1 and G3 as regard the social age (P>0.05).

Age with months

Language ageLanguage age

43

23

57

10

20

30

40

50

60

70

80

G1 G2 G3

A statistical significant differences were obtained between G1

and G2 as regard the language age (P>0.05).

A high statistical significant differences were obtained

between G1 and G3 as regard the language age(P>0.05).

TSH levelTSH level

1.6

14.3

0.61

3

5

7

9

11

13

15

17

19

G1 G2 G3

A statistical significant differences were obtained between G1

and G2 as regard the TSH level(P>0.05).

A high statistical significant differences were obtained

between G1 and G3 as regard the TSH level (P>0.05).

T4 levelT4 level

1.20.6

1.8

0

1

2

3

4

5

G1 G2 G3

A statistical significant differences were obtained between G1

and G2 as regard the T4 level (P>0.05).

A high statistical significant differences were obtained

between G1 and G3 as regard the T4 level (P>0.05).

The audiological assessmentThe audiological assessment::

Non-statistical significantNon-statistical significant difference was obtained difference was obtained

between the two groups as regard the audiological between the two groups as regard the audiological

evaluation (P. evaluation (P. << 0.05). 0.05).

II: CorrelationsII: Correlations::

A high A high positivepositive significant correlation was obtained significant correlation was obtained

between the language , mental, social age and IQ in between the language , mental, social age and IQ in

correlation with the level of correlation with the level of T4T4 in G1 and G2 (r=0.76). in G1 and G2 (r=0.76).

A high A high negativenegative significant correlation was obtained significant correlation was obtained

between the language , mental, social age and IQ in between the language , mental, social age and IQ in

correlation with the level of correlation with the level of TSHTSH in G1 and G2 (r=-0.87). in G1 and G2 (r=-0.87).

DiscussionDiscussion

This study aimed at investigating the language This study aimed at investigating the language

developmental outcomes of the children with congenital developmental outcomes of the children with congenital

hypothyroidism (hypothyroidism (study groupstudy group) in comparison to the ) in comparison to the

children who with normal thyroid functional (children who with normal thyroid functional (control control

groupgroup). The two groups were matched as possible in ). The two groups were matched as possible in

their sociodemographic data (their sociodemographic data (age and sexage and sex) in order to ) in order to

show the effect of the hypothyroidism in the language show the effect of the hypothyroidism in the language

abilities of their children.abilities of their children.

In this study, there was In this study, there was significantsignificant difference difference

between the hypothyroid and normal thyroid between the hypothyroid and normal thyroid

functional children as regard the functional children as regard the IQ , mental and IQ , mental and

social agesocial age. Moreover , There was . Moreover , There was high high

significantsignificant difference between the controlled difference between the controlled

hypothyroidism and non- controlled hypothyroidism and non- controlled

hypothyroid functional children as regard the hypothyroid functional children as regard the IQ IQ

, social and mental age, social and mental age..

This result matched to This result matched to Glorieux et al, (1988)Glorieux et al, (1988) who who

found that, the hypothyroid group had scientifically found that, the hypothyroid group had scientifically

lower mean global quotient than the control group. lower mean global quotient than the control group.

They said that their results may represent the They said that their results may represent the

manifestations of brain damage occurs even with early manifestations of brain damage occurs even with early

detection and treatment of hypothyroidism. Also, detection and treatment of hypothyroidism. Also,

Koibuchi and Chin, ( 2000)Koibuchi and Chin, ( 2000) found that the children with found that the children with

severe CH, had mean IQ scores 10 to 22 points below severe CH, had mean IQ scores 10 to 22 points below

that of their siblings .that of their siblings .

AlsoAlso, Nacfau et al (2005), Nacfau et al (2005) found that the CH children found that the CH children

who were being treated for hypothyroidism starting who were being treated for hypothyroidism starting

before the age of before the age of 2 years2 years. Their IQ scores lay within the . Their IQ scores lay within the

normal range ( 71- 122; mean 92.4), but 77% showed at normal range ( 71- 122; mean 92.4), but 77% showed at

least one sign if impaired brain function. least one sign if impaired brain function. ClumsinessClumsiness

was found in 33%, was found in 33%, behaviour disordersbehaviour disorders in 23%, in 23%,

language disorderslanguage disorders in 20%, in 20%, learning disorderslearning disorders in 26%, in 26%,

squintsquint in 53%, in 53%, nystagmusnystagmus in 10%, and in 10%, and minor motor minor motor

disordersdisorders in 50%. in 50%.

In the other handIn the other hand, Heyerdal et al, (1991) , Heyerdal et al, (1991) found that found that

even with early recognition and treatment of even with early recognition and treatment of

congenital hypothyroidism, these children are slower congenital hypothyroidism, these children are slower

in development than the normal children. they in development than the normal children. they

concluded that congenital hypothyroidism affect the concluded that congenital hypothyroidism affect the

brain development before birth. Some of these effects brain development before birth. Some of these effects

last after birth even if the replacement therapy is last after birth even if the replacement therapy is

given regularly since birth.given regularly since birth.

The results obtained from the Arabic language test The results obtained from the Arabic language test

revealed a revealed a significant differencesignificant difference between the between the

hypothyroidism and normal thyroid functional children hypothyroidism and normal thyroid functional children

as regard the as regard the language agelanguage age. Moreover , There was . Moreover , There was high high

significantsignificant difference between the controlled difference between the controlled

hypothyroidism and non- controlled hypothyroid hypothyroidism and non- controlled hypothyroid

functional children as regard functional children as regard language agelanguage age. These . These

results are in agreement with those ofresults are in agreement with those of Glorieux et al, Glorieux et al,

(1988)(1988) , Fuggle et al (1988), Fuggle et al (1988) and and Rovet et al,(1992Rovet et al,(1992),),

Miller et al ( 2002)Miller et al ( 2002) revealed that the treated revealed that the treated

hypothyroid group had significant increased hypothyroid group had significant increased

verbal memory retrieval. Results suggest that verbal memory retrieval. Results suggest that

specific memory retrieval deficits associated specific memory retrieval deficits associated

with hypothyroidism can resolve after with hypothyroidism can resolve after

replacement therapy with levothyroxine.replacement therapy with levothyroxine.

But But our result not matched toour result not matched to Denman (1984)Denman (1984) who who

found that the CH group did not differ from control found that the CH group did not differ from control

children on tests of children on tests of phonological processingphonological processing

(WJRMT Word Attack), (WJRMT Word Attack), writingwriting (test of written (test of written

language ( TOWL), or language ( TOWL), or spellingspelling ( WRAT_R spelling). ( WRAT_R spelling).

The results of the supplementary tests also The results of the supplementary tests also

indicated no difference in indicated no difference in languagelanguage and and memorymemory

tasks.tasks.

Rovet et al., (1995)Rovet et al., (1995) indicate that the indicate that the

neuropsychological functioning of neuropsychological functioning of

children with congenital children with congenital

hypothyroidism (CH) is affected by hypothyroidism (CH) is affected by

factors associated with the disease factors associated with the disease

and its treatment. and its treatment.

Their nonverbal or visuospatial intellectual abilities Their nonverbal or visuospatial intellectual abilities

were sensitive to the were sensitive to the etiologyetiology of hypothyroidism, of hypothyroidism,

whereas several aspects of memory were sensitive whereas several aspects of memory were sensitive

to the to the timingtiming of thyrotropin (TSH) normalization. of thyrotropin (TSH) normalization.

With regard to With regard to etiologyetiology, children with athyreosis , children with athyreosis

scored significantly below the other groups on scored significantly below the other groups on

indices of nonverbal intelligence and arithmetic indices of nonverbal intelligence and arithmetic

achievement. achievement.

Cohen (1997)Cohen (1997) concluded that the important of the age at concluded that the important of the age at

normalization of TSH affected selective aspects of normalization of TSH affected selective aspects of

memory and attention functioning. Specifically, children memory and attention functioning. Specifically, children

with CH who normalized by with CH who normalized by I to 2 monthsI to 2 months of age, scored of age, scored

higher than those normalizing later on indices of higher than those normalizing later on indices of

immediate and delayed visual memory and attention. immediate and delayed visual memory and attention.

While, children who normalized by While, children who normalized by 3 months3 months of age of age

performed better than those normalizing past this age performed better than those normalizing past this age

on indices of global memory, visual memory and on indices of global memory, visual memory and

learning.learning.

The study revealed that, A high The study revealed that, A high positive significant positive significant

correlationcorrelation was obtained between the language , was obtained between the language ,

mental, social age and IQ in correlation with the mental, social age and IQ in correlation with the

level of level of T4T4 in the study group, Also, A in the study group, Also, A high negative high negative

significant correlationsignificant correlation was obtained between the was obtained between the

language , mental, social age and IQ in correlation language , mental, social age and IQ in correlation

with the level of with the level of TSHTSH in the study group. in the study group.

This result is matched to This result is matched to Kooistra et al Kooistra et al

(1995)(1995) showed Significant correlations showed Significant correlations

between the start of therapy and both between the start of therapy and both

motor scores and performance IQ scores at motor scores and performance IQ scores at

the age of 7 years in children with severe the age of 7 years in children with severe

hypothyroidism. hypothyroidism.

Also, Also, Soon and Song (2001)Soon and Song (2001) observed that children's observed that children's

thyroid hormone levels at the time of testing were thyroid hormone levels at the time of testing were

positively correlated with indices of memory, positively correlated with indices of memory,

language, speed of processing, and fine motor language, speed of processing, and fine motor

performance, whereas TSH levels were negatively performance, whereas TSH levels were negatively

associ ated with receptive language and recognition associ ated with receptive language and recognition

memory skills. memory skills.

Conclusion& RecommendationConclusion& Recommendation

There is evident that the children with congenital There is evident that the children with congenital

hypothyroidism show poorer language development hypothyroidism show poorer language development

in comparison to normal children, moreover the in comparison to normal children, moreover the

children with uncontrolled congenital children with uncontrolled congenital

hypothyroidism show worsen in language, mental, hypothyroidism show worsen in language, mental,

social age and IQ in comparison to that children with social age and IQ in comparison to that children with

controlled hypothyroidism and normal children.controlled hypothyroidism and normal children.

The need for diagnosis and treatment of children The need for diagnosis and treatment of children

with congenital hypothyroidism as soon after birth with congenital hypothyroidism as soon after birth

as possible, preferably no later than the second as possible, preferably no later than the second

week of life .it is also important to screen week of life .it is also important to screen

hypothyroid children for hearing problems and to hypothyroid children for hearing problems and to

provide remediation in language. provide remediation in language.

The present study provide several challenges for the The present study provide several challenges for the

behavioral pediatrician who may have children with behavioral pediatrician who may have children with

congenital hypothyroidism in his or her practice. It is congenital hypothyroidism in his or her practice. It is

important to monitor these children frequently and important to monitor these children frequently and

closely to ensure thyroid hormone levels closely to ensure thyroid hormone levels

maintained .maintained .