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University of Khartoum

Faculty of Medicine
Post graduate Medical Studies Board

Frequency rate of thyroid disease and other


associated conditions in children with Down's
Syndrome in Khartoum State

By
Dr. Gubartella Mohammed Zein Babiker
M.B.B.S (University of Khartoum)

A thesis submitted in partial fulfillment for the requirements of the Degree of


Clinical MD in Paediatrics and Child Health,
April, 2004

Supervisor
Dr. El Tahir Medani El Shibly
Associate Prof.- Consultant Pediatrician
M.P.H (Harvard, America)
M.D (U. of K.)
FRCPCH (London)
M.P.C.H and M.B.B.S (U. of K.)

(

)(78

To
my lovely parents,
my family
&
all innocent, happy, friendly children with Down's syndrome
whom I love

I am deeply grateful to my supervisor Dr. Etahir Medani


Elshibly, Associate Prof. of paediatrics, University of Khartoum, who
kindly directed me forwards and guided me in doing this work.
I would like to thank Dr. Ali Arabi, he was kind and helpful.
I wish to thank all teachers of respective Institutes and
schools for their patience and support.
I am greatly indebted to Mr. Yousif Ali Yousif and Dr. Elfatih
Yaagoub and the working staff in the Radiation and Isotopes Center,
Khartoum (RIC).
I wish to express my appreciation and thanks to all children
with Down's syndrome and their parents who were the core of the
study and willing to make this work possible.
I would like also to extend my thanks to Miss Widad
A/Magsood for typing this manuscript.

ABBREVIATIONS

ACHT

Acquired hypothyroidism

CHD

Congenital heart diseases

CHT

Congenital hypothyroidism

CNS

Central nervous system

DIT

Di-iodotyrosine

DM

Diabetes mellitus

DNA

Deoxyribonucleic acid

DS

Down's syndrome

FT4

Free T4

MID

Monoiodotyrosine

mu/L

Micro-unit per litre

IQ

Intellectual quotient

PCR

Polymerase cell reaction

rT3

Reverse Tri-iodothyronine

T3

Tri-iodothyronine

T4

Thyroxin

TSH

Thyroid stimulating hormone

TBG

Thyroxin binding globulin

TRH

Thyroxin -releasing hormone

T3RU

Tri-iodothyronine resin uptake

UE3

Unconjugated estriol

ABSTRACT

Thyroid disturbances is a well recognized association with


Down's syndrome.
This study is descriptive cross-sectional facility-based study,
aimed to determine the frequency rate of common thyroid
disturbances in children with Down's syndrome. It was conducted in
most hospitals in Khartoum State and in seven institutes for children
with special needs and rehabilitation schools in Khartoum and
Omdurman cities, in the period from 1st of April 2002 to 31st of march
2003.
The total of 96 children with DS, aged < 16 years, male to
female ratio was 1.34: 1.
All children in the study were surveyed and investigated for
thyroid function by measuring TSH, T4 and T3 levels.
Frequency of thyroid disturbances was 38 (39.6%), twenty
(20.8%) had definite hypothyroidism, 17(17.7%) had evidence of
thyroid dysfunction and subclinical hypothyroidism and one (1%) had
hyperthyroidism. Two neonates had congenital hypothyroidism, no
significant sex association was found. There was poor correlation

between clinical symptoms and biochemical thyroid dysfunction.


Other associated conditions in children with Down's syndrome and
thyroid diseases were congenital heart diseases, diabetes mellitus,
alopecia cataract and genitourinary tract anomalies.


.

.

2002/4/1 2003/3/31.
16
96
: .1 : 1.34
: ) (TSH
) (T4, T3 (%39.6 ) 38
) (% 20.8 (%17.7)17
.
.


.
:
.

LIST OF FIGURES
Page No.
Fig. 3.1

Age and sex distribution of the study group

Fig. 3.2

Distribution of study group according to social status 57

Fig. 3.3

Child education distribution of the study group

Fig. 3.4

Distribution of the study group according to


parent's consanguinity

Fig. 3.5

59

60

Distribution of children in the study according to


height centile

Fig. 3.7

58

Distribution of children in the study according to


weight centile

Fig. 3.6

56

61

Distribution of children in the study according to


thyroid status

62

LIST OF TABLES
Page No.
Table 3.1: Distribution of mothers' age at time of conception
of the study group

63

Table 3.2: Distribution of fathers' age at time of conception


of the study group

64

Table 3.3: Distribution of the study group according to


fathers' education

65

Table 3.4: Distribution of the study group according


to mothers' education

66

Table 3.5: Distribution of the study group according


to fathers' occupation

67

Table 3.6: Distribution of the study group according


to mothers' occupation

68

Table 3.7: Distribution of birth order in the study group

69

Table 3.8: Distribution of number of sibs of children in


the study group

70

Table 3.9: Distribution of the study group according


to gestational age

70

Table 3.10: Frequencies of common symptoms of thyroid disorders in


DS in the study children

71

Table 3.11: TSH and T4 levels for the study group compared to
the age specific range

72

Table 3.12: Frequencies of TSH ranges in the study group with high
TSH and normal T4 levels

72

Table 3.13: Frequencies of TSH ranges in the study group with high
TSH and low T4 levels

73

Table 3.14: Frequencies of T4 levels of the study group compared


to age specific ranges

73

Table 3.15: Frequencies of T3 levels of the study group compared


to age specific ranges

74

Table 3.16: TSH level of the different age groups of the children
in the study

74

Table 3.17: T4 level of the different age groups of the children


in the study

75

Table 3.18: Thyroid disturbances in relation to sex among


children in the study

75

Table 3.19: Common symptoms of thyroid disorder in DS found in


children with thyroid disturbances in the study
Table 3.20: Associated conditions among children with thyroid
disturbances in the study group

76
77

TABLE OF CONTENTS
Page
Dedication....I
AcknowledgmentII
List of Abbreviations.....III
English Abstract....V
Arabic Abstract.........VI
List of Figures.....VII
List of Tables ....VIII

CHAPTER ONE
1. INTRODUCTION AND LITERATURE REVIEW......1
1.1. Historical background

1.2. Epidemiology

1.3. Incidence

1.4. Cytogenic and pathogenesis of DS

1.4.1. Types of defects

1.4.1.1. Regular trisomy 21 or (non-dysjunction)

1.4.1.2. Translocation

1.5. Pathophysiology

1.6. Clinical features

1.6.1. Abnormalities
1.6.2. Occasional abnormalities

8
10

1.6.3. Principal features in newborn & diagnosis and


case definition

11

1.6.3.1. Diagnostic index for DS

12

1.6.3.2. Prenatal screening for trisomy 21 (DS)

12

1.7. Natural history

14

1.7.1. Mental retardation

14

1.7.2. Social development

15

1.7.3. Motor development

15

1.7.4. Sexual development

15

1.7.5. Speech development

15

1.7.6. Growth

16

1.7.7. Life expectancy

16

1.8. Thyroid gland

18

1.8.1. Histological structure

18

1.8.2. Normal thyroid development & thyroid


hormones synthesis

19

1.8.3. Regulation of thyroid synthesis

20

1.8.3.1. Neural control of pituitary-thyroid function

20

1.8.3.2. Auto-regulation of the thyroid gland

21

1.8.4. Hormone synthesis

21

1.8.5. Hormone degradation

22

1.8.6. Hormone transport

22

1.8.7. Cellular effect

23

1.8.8. Thyroid function tests

23

1.8.8.1. Static test

23

1.8.8.2. Dynamic tests

24

1.8.8.3. Radiologic studies

25

1.8.9. Abnormal thyroid functions


1.8.9.1. Hypothyroidism

25
25

1.8.9.1.1. Congenital hypothyroidism (CHT)

26

1.8.9.1.2. Acquired hypothyroidism (AHT)

27

1.8.9.2. Compensated hypothyroidism

28

1.8.9.3. Hyperthyroidism

28

1.8.10. Management of thyroid disorder

29

1.8.10.1. Hypothyroidism

29

1.8.10.2. Hyperthyroidism

30

1.8.10.3. Subclinical hypothyroidism

30

1.9. Down syndrome and thyroid disturbances


1.9.1. Prevalence studies

30
30

1.9.1.1. Congenital hypothyroidism (CH)

32

1.9.1.2. Acquired hypothyroidism

33

1.9.1.2.1. Clinical features

34

1.9.1.3. Hyperthyroidism

35

1.9.2. Other conditions possibly associated with DS and


thyroid disorders
1.9.3. Treatment of thyroid disorder in DS

36
36

JUSTIFICATION

38

OBJECTIVES

39

CHAPTER TWO
2. PATIENTS AND METHODS

40

2.1. Study design

40

2.2. Study area

40

2.3. Study duration

41

2.4. Study Population

41

2.5. Case definition

41

2.6. Inclusion criteria

41

2.7. Exclusion criteria

41

2.8. Sample

42

2.8.1. Size

42

2.8.2. Design

42

2.9. Study techniques

42

2.9.1. Consent

42

2.9.2. Research team

43

2.9.3. Input of the author

43

2.9.4. Research tools

43

2.9.4.1. Data collection technique

43

2.10. Data entry and statistical methods

44

2.11. Budget

44

2.12. Encountered difficulties

45

CHAPTER THREE
3. RESULTS
3.1. Socio-demographic characteristic

46

3.1.1. Age and sex characteristic of the study population

46

3.1.2. Description of the social status of the study group

46

3.1.3. Mother's age at the time of conception

46

3.1.4. Fathers' age at time of conception

47

3.1.5. Child education

47

3.1.6. Fathers' education

47

3.1.7. Mothers' education

48

3.1.8. Fathers' occupation

48

3.1.9. Mothers' occupation

48

3.1.10. Parents consanguinity

49

3.1.11. Childbirth order

49

3.1.12. Number of sibs

49

3.1.13. Number of abnormal sibs (dysmorphic or retarded)

49

3.1.14. Family history of abnormal members

49

3.1.15. Gestation age for children in the study

49

3.1.16. History of irradiation during pregnancy

49

3.1.17. Weight centile for children in the study

49

3.1.18. Height centile for children in the study

49

3.2. Frequencies of common symptoms of thyroid disorder in DS


in the study group

50

3.3. Associated conditions

50

3.4. Clinical pattern of thyroid disturbances

51

3.4.1. Types of thyroid disorder in the study group

51

3.4.2. TSH levels

51

3.4.3. T 4 levels

52

3.4.5. T3 levels

52

3.4.5. Age and thyroid disturbances

52

3.4.6. Sex and thyroid disturbances

53

3.4.7. Common symptoms of thyroid disorders in DS found


in children with thyroid disturbances in the study

53

3.4.8. Associated condition among children with thyroid


disturbances in the study group

55

CHAPTER FOUR
4. DISCUSSION

78

4.1. Frequencies and sociodemographic characters

78

4.2. Clinical pattern

79

4.3. Clinical symptoms

79

4.4 Associated condition in DS children with thyroid


disturbances in the study group

82

CONCLUSION

84

RECOMMENDATIONS

85

REFERENCES

87

APPENDIX (Questionnaire)

INTRODUCTION AND LITERATURE REVIEW

Trisomy 21 or Downs syndrome (DS) is the most common


autosomal chromosome abnormality in live born infants, the most
frequent and best known trisomy in human(1,2). Despite the fact that
more than half of the trisomy 21 conceptions abort early in
pregnancy(2). It is the single most common cause of severe learning
disability, accounting for one third of all cases of learning disability(3).
In Sudan it was found that DS is the most frequent cause of mental
retardation

in

institulized

retardation,

hypotonia,

mentally

dysmorphic

retarded
facial

children.(4)Mental

features

and

other

phenotypic traits characterize the syndrome(2,5).

1.1. Historical background:


Seguin(6) described the condition now known as DS as
(Furfuranceous) cretinism, in an attempt to differentiate the condition
from that of stable cretins. Unintentionally, therefore, over one
hundred and thirty years ago a link between DS and thyroid disease
had been proposed.

John Langdon Down influenced by the then prevalent racial


hypothesis, described the condition now bears his name, as
Mongols (look like people coming from Mongolia) and thought that
the affected people were a form of regression in evolution(7). During
the early part of last century other endocrine disorder were implicated
in the etiology of DS.

Some author suggested that pituitary

dysfunction was the main factor in the pathogenesis(8,9). The matter


was finally resolved when in 1959 Lejeune and his co-workers
demonstrated that the syndrome was a result of trisomy of
chromosome 21(10). It is only since then Mongols are known to have
fourty-seven instead of fourty-six chromosomes in their cells. One of
Dr. John Langdon Down central contributions to people with DS came
with his differentiation of infantile hypothyroidism disease from
trisomy 21 with recognition of two of the sources of childhood
disability came the beginning of real opportunity to sort out causes
and possibilities for treatment of some of the major conditions that
affect children(7,11).
The relation between DS and thyroid function has remained
close and interwind in several ways. At several periods over the past
hundred odd years thyroid hormone therapy has been advocated for

treatment of a variety of syndromes lumped as mental retardation


and some individuals with Down's syndrome have probably benefited.
The association of thyroid pathology with DS has become well
recognized and many studies have explored various aspect of
association(11).

At the turn of the last century, a pathological

association between DS and thyroid disorders was described by


Bournville (1903)(12). Clinical and histopathiological confirmation soon
followed (Hill 1908, Gordon 1930, Pannacchietti 1935, Benda 1949)
(13,14,15,16)

. However the first case of a person with DS and clinical

hyperthyroidism was reported by Gilehrist in 1946 and of clinical


hypothyroidism by Maranon et al in 1951(17,18). At the turn of the last
millennium thyroid disease in the DS population continues to be the
focus of ongoing interest and research (Kennedy et al 1992) (19).

1.2. Epidemiology:
It occurs in all areas of the world, no known ethnic predilection
exists.(20)There is an increased male to female ratio (1.15 : 1) in new
born with DS(21).

1.3. Incidence:
The incidence of DS is approximately one in 600-800 live
births(2,5). The incidence is estimated to be more than twice as high

among all conceptions than it is among live births. More than half of
the trisomy 21 conceptions abort early in pregnancy(2). The
occurrence of trisomy 21 increases with advancing maternal age(2)
(see the table).
Incidence of trisomy 21 at birth in relation to maternal age(5).
Maternal age

Incidence

15-29

1:1500

30-34

1:800

35-39

1:270

40-44

1:100

>45

1:50

1.4. Cytogenic and pathogenesis of DS:


Majority of individual with DS carry 47 chromosomes. The
extra chromosome being what was designated as chromosome 21(2),
they have 3 copies of chromosome 21. Trisomy to all or part of
chromosome 21 is present(1).

1.4.1. Types of defects:1.4.1.1. Regular trisomy 21 or (non-dysjunction):The majority of cases (95%) have 3 fine standing copies of
chromosome 21, usually arises from the failure of paired (replicated)
chromosomes to separate (mitotic non-dysjunction) one cell end with
only one copy (monosomic) and the other with 3 copies (trisomic) of
the specific chromosome(1,2,5). Occasionally, normal separation
occurs but one member fails to migrates, this is known as (anaphase
log)(22). The risk of having a child with extra chromosome 21
increases with advancing maternal age. This risk rises dramatically
after 35 years of age. Most children with trisomy 21 are born to
women younger than 35 years of age, however, because most
women give birth before 35 years of age(23).
The mechanism of increased incidence of trisomy 21 in
foetuses of older mothers is not understood. The extra chromosome
come from the father in only a small percentage of cases.

The

recurrence risk for parent of children with trisomy 21 increases to 1%2% (unless age-related risk is greater) (23).

1.4.1.2. Translocation:
2 - 4% are due to the transfer of a chromosome material to
form one chromosome to another chromosome. It may be centre
fusion (Robertsonian) or reciprocal. The majority of translocation that
give rise to DS involve the translocation of the third number 21
chromosome to another chromosome (Fusion at the centromere)
usually a D-group (number 13,14 or 15) or a G-group (number 21 or
22) chromosome(5,23).
(i)

Of all cases of translocation to are de novo (i.e. not


familial).

(ii)

- of translocation cases are familial, meaning that


one of the parent has a balanced translocation involving one
number 21 chromosome and another chromosome. In these
cases, the recurrence risk may be as high as 15% in future
pregnancies(2,23). Translocation accounts for 9% of the children
with DS born to mothers younger than 30 years of age(2).
Phenotype in translocated DS is not distinguishable from that
of regular trisomy 21 DS individuals.

(iii)

Mosaicism:

about 1% of children with DS has

chromosome mosaicism, with some cells normal and some

cells trisomic.

It results from a mitotic division error that

occurred during early embryonic development(2,5,23).

The

phenotypic expression of such mosaic karyotype ranging from


mild clinical presentations to those showing typical DS(2).

1.5. Pathophysiology:The extra chromosome 21 affects almost every organ system


and results in a wide spectrum of phenotypic consequences. These
include life-threatening complications, significant alteration of life
cause (e.g. mental retardation), and dysmolrphic physical features.
DS Syndrome results in decreased prenatal viability and increased
prenatal and post natal morbidity, children are delayed in their
physical

growth,

maturation,

bone

development

and

dental

eruption(1,24,25).
The presence of an extra copy of the proximal part of 21 and
22, 3 region appear to result in the typical physical phenotype: mental
retardation, characteristic facial features, hand anomalies and
congenital heart defects. Molecular analysis revealed that 21& 22, 1922, 3 region appears to contain gene(s) responsible for the
congenital heart disease observed in DS(24,26,27). The new gene
(DSCR1); identified from region 21 & 22, 1-922, 2 is highly expressed

in the brain and heart and is involved in the pathogenesis of DS, in


particular, mental retardation and/or cardiac defects(27).

Abnormal

physiological functions affect thyroid metabolism and intestinal


malabsorption(28). Frequent infections are presumably due to impaired
immune responses and there is increased incidence of autoimmunity
including hypothyroidism and rare Hashimoto thyroiditis.

Diabetes

mellitus develops in many affected patients. Premature senescence


causes cataracts and Alzheimer disease. Bone marrow dysfunction
is indicated by leukomoid reactions of infancy and increased risk of
acute leukaemia(29).

1.6. Clinical features:


Children with DS have a characteristic appearance that can
be defined in terms of their dysmorphic features. They also have a
number of other characteristic functional and structural abnormalities,
that are part of the syndrome(23).
1.6.1. Abnormalities:(5)
General:

- Hypotonia.

Small

open

protruded tongue.
-

Diastasis recti.

mouth

and

Hyperflexibility of joints.

Short stature.
CNS:

- Mental deficiency.

Craniofacial:

- Brachycephaly.

Flat faces profile.

Flat occipit.

Microcephaly.

Up slanting palberal fissures.

Thin

cranium

with

wide

fontanels and delayed closure.


-

Hypoplasia

to

aplasia

of

frontal sinuses.
-

Small nose with depressed


nasal bridge.
Eyes:

Speckling iris (Brushfields spots) with peripheral


hypoplasia of iris.

Fine lens opacities (by slit


lamp examination) 59% refractive errors.
Ears:

- Small, over-folding of angulated upper helix.

Dentation:

- Hypoplasia, irregular placement.

art:

Neck:

- Short neck.

Hands:

- Short hand, hypoplasia of fifth finger (60%).

Clinodactyly (50%).

Simian crase (45%), single


crease 40%.

Distal

position

of

palmar

axial triradius (84%).


-

Ulnar

loop

dermal

ridge

pattern on all digits (35%).


Feet:

- Wide gap between 1st and 2nd toes.


planter crease between 1st

and 2nd toes.


-

Open

field

dermal

ridge

pattern in hallucal area sole (50%).


Pelvis:

- Hypoplasia.

- Anomaly in about 40%, atrioventricular communis,


ventricular

septal

defect,

patent

ductus

arteriosus, ventricular septal defect.


Skin:

- Loose folds in posterior neck (infancy).

Hair:

- Fine, soft and often sparese.

Genitalia:

- Small penis, hypogonadism (infertility 100%).

1.6.2. Occasional abnormalities:


Seizures less than 5%. Strabismus 33%, nystagmus 15%,
keraconus 6%. Cataract 1.3%, low set ears, web neck, funnel chest,
tracheo-esophageal fistula, duodenal atresia, tetralogy of fallot,
incomplete fusion of vertebral arches of lower spine 37%. Only 11
ribs, cryptorchidism, syndactyly of 2nd and 3rd toes. The incidence of
leukaemia is close to 1%(5). Hirschsprung's disease(28), obstructive
sleep

apnea,(29)

dementia,(30)

atlantoaxial

instability.(31)Thyroid

disorders are more common, diabetes mellitus (DM)(5,32).


1.6.3. Principal features in newborn & diagnosis and case definition:
The diagnosis can be made shortly after birth. The following
ten features of DS in the new born are set forth by Hall who found at
least four of these abnormalities in all new born and six or more in
89% of them(33):Hypotonia

80%.

Poor moro reflex

85%.

Hyperflexibility of joints

80%.

Excess skin on back of neck

80%.

Flat facial profile

90%.

Slanted palpebral fissures

80%.

Anomalous auricles

60%.

Dysplasia of pelvis

70%.

Dysplasia of mid-phalanx of fifth finger

60%.

Simian crease

45%.

1.6.3.1. Diagnostic index for DS:


Also there is a diagnostic index made by Rex A.P., Preus M. for
fast clinical diagnosis(34). The features are:3 dermatoglyphic traits (hallucal and forefinger pattern
and Palmer triradius).
2 physical traits (ear length and internipple distance).
3 other clinical findings (Brush field spots, wide spaced
first toe and excess back neck skin).
This index can diagnose 95% of patients who are suspected
of having the syndrome with confidence of 99.9%.
1.6.3.2. Prenatal screening for trisomy 21 (DS):
Screening for foetal aneuploidy has evolved from a risk
assessment based on maternal age to the present approach, which
uses ages and levels of maternal serum analysis.

In second trimester, levels of alpha-fetoprotein, human


chorionic gonadotropin and unconjugated estriol are used to refine
estimates of risk based on maternal age, and this approach will
identify approximately 65% of foetuses with DS, with false +ve rate of
4.5-5% over the past 5 years(35). Inhibin A has been added by many
laboratories, and may increase the rate of detection to 75%(36). Over
the past five years first trimester screening approaches have been
developed. The use of maternal age and levels of two biochemical
analysis, pregnancy associated plasma protein A and the three B
subunit of human chorionic gonadotropin has resulted in a detection
rate of 60-65% for trisomy 21(37).
Ultrasonographic measurement of foetal nuchal translucency,
when combined with maternal age can independently detect 77% of
case of DS with similar false positive rate of 5%(38).
Mathematical modeling has suggested that combining the
measurement of biochemical analysis and nuchal translucency during
the first trimester may identify up to 89% of cases of DS, with false
positive rate of 5%(39,40).
Prenatal diagnosis of foetal trisomies is usually performed by
cytogentic analysis from amniotic fluid (aminocentesis) between

14th-18th weeks of pregnancy in big risk mother, also can be done by


chorionic villus sampling between 14th-18th weeks of pregnancy.
Fluorescent polymerase cell reaction (PCR) and short tandem
repeats:
it is a rapid method even from single foetal cell, can diagnose
DS within 24 hours of amniocentesis or from foetal cells isolated from
maternal blood(41). In general the invasive methods should be
administered to high-risk group only. In less than 35 years maternal
age maternal serum screening can be used(2).

Mothers blood is

checked for three items, alpha-fetoproteins will be decreased


especially after 20 weeks, unconjugated estriol (UE3), will be
decreased, human chorionic gonadotrophin: total HCG is increased in
2nd trimester but better in 1st trimester(2,40).

1.7. Natural history:


1.7.1. Mental retardation:
Childrens with Down Syndrome have moderate to severe
mental retardation with an intellectual quotient (IQ) in range of 20-75
(mean IQ is approximately 50).(5,42) DS children under 3 years had a
developmental quotient above 50 whereas none of those in the three
to nine years group had IQ above 50, though the range is generally

said to be 25-50.

The mean IQ for older patients is 24(5). Thus

intellectual function shows a decline with age in adult with DS


attributed to a presenile dementia.

It is therefore, particularly

interesting to note the relationship between DS and Alzheimers


disease(43).

1.7.2. Social development:


Social performance is usually beyond the expected for mental
age, generally they are good babies are often affectionate and good
humored happy children, they tend toward mimicking, are friendly,
have a good sense of rhythm and enjoy music. 13% have serious
emotional problems.(5)
1.7.3. Motor development:
Children with DS are hypotonic, muscle tone tends to
improve with age, but the early developmental milestones are
eventually reached(1,5,42).
1.7.4. Sexual development:
The development of secondary sexual characteristic is
delayed in DS. The girls can menstruate and can be fertile, whereas

the males are considered infertile and have relatively low serum
testosterone values(5,42).
1.7.5. Speech development:
It is slower than motor activity. The DS child uses words and
possibly phrases at 3 years but rarely speaks in sentences before 4-6
years. Coordination is often poor, and the voice tends to be
raucous(5).
1.7.6. Growth:
Growth in children with DS differs markedly from that of
normal children(44,45). Short stature is a cardinal feature of DS(45).
The growth retardation of children with DS commences prenatally(46).
After birth growth velocity is most reduced between 6 months and 3
years of age(45,47). Puberty generally occurs somewhat early and is
associated with an impaired growth spurt(45,48). During the first eight
years secondary centres of ossification are often late in development.
During the later childhood the osseous maturation is more normal
and final height is usually attained around 15 years of age(5).
Statural growth is a well known indicator of health during childhood.
As growth and final height differs markedly between children with DS
and

healthy

children,

standard

growth

charts

have

been

developed(45,49,50). The American Growth Charts are frequently used


allover the world(44). For the majority the cause of growth retardation
is not known(51). Some condition leading to poor growth (congenital
heart disease,(52,53)sleep related upper airway obstruction,(54) celiac
disease,(55,56)thyroid

hormone

deficiency,(57,58)and

nutritional

inadequacy caused by feeding problems(59,60) occur more frequently


among those with the syndrome. There is also high prevalence of
overweight/obesity, particularly in adolescence and adult life(61,62).
1.7.7. Life expectancy:
Life expectancy of DS population is reduced compared to
general population. Approximately 85% of infants survive to one year
and 50% can be expected to live longer than 50 years.
The major cause of early mortality is congenital heart defects,
44% of those with cardiac anomalies die in infancy, between infancy
and 40 years of age mortality rate is not much greater than the
normal, expectancy for DS reach a relative plateau during the 20s,
when they reach 30s more than 30% experience dementia
characterized by rapid deterioration of mental and emotional health.
In addition to the congenital heart disease, oesophageal
atresia, Hirschsprung disease, duodenal atresia and leukaemia

contribute to mortality. Infections may pose a serious problem and


greatly increase morbidity.
Atlantoaxial instability may result in irreversible spinal cord
damage, visual and hearing impairments in addition to the presence
of mental retardation may further limit the child's overall functioning.
Unrecognized thyroid dysfunction may further compromise central
nervous system function. However, in recent years the survival
improved by improving medical, surgical and social care.(5,63)

1.8. Thyroid gland:


The thyroid gland is a flat-appearing bilobed, pink structure,
lying on either side of the trachea lateral and inferior to the thyroid
cartilage(64).
1.8.1. Histological structure:
The fundamental unit of fully developed thyroid is the follicle,
which is a roughly spherical mass of colloid surrounded by a shell
consisting of a single layer of epithelial cells and often bordering
several isolated colloid masses(65).
The thyroid stroma is very rich in vessels that form extensive
capillary plexuses lying to the basement membrane. There is also a

network of lymphatics in the gland. The stroma encloses a number of


nerve fibres, some are parasympathetic but most are sympathetic(64).
The epithelial cells and the follicular cells vary in height,
depending on the intensity of stimulation by pituitary thyrotropin
(TSH), between squamous and columnar cells. They produce the
thyroglobulin, a glycoprotein matrix on which the hormones are
synthesized, in addition to the active thyroid hormones themselves,
thyroxin (T4) and triiodothyronine (T3). A second variety of cells the
parafollicular cells or c-cells are present in low numbers and produce
a peptide hormone, calcitonin that exerts a hypocalcemic action(64).
These cells are embryologically derived from the neural crest and
thus are not truly thyroid in origin.
1.8.2. Normal thyroid development & thyroid hormones synthesis:
The thyroid gland first appear in the fourth week of gestation
as an epithelial proliferation of the endoderm of the foregut, and at
this time the synthesis of thyroglobulin begins.

The thyroid then

penetrates the mesoderm and migrates downward. By the seventh


week of development, the now bilobed gland reaches its normal
position anterior to the trachea. By the tenth to eleventh week, the
fetal thyroid begins to and oxidize iodine, and by the twelfth week,

colloid formation is detectable. By the eleventh week of gestation,


the thyroid gland secretes (T4) and (T3). By the thirteenth week,
thyroxin-binding globulin (TBG) and (TSH) are detectable in serum.
Maturation of the fetal hypothalamic-pituitary-thyroid axis usually
occurs by the twentieth week of gestation(66,67).

1.8.3. Regulation of thyroid synthesis:


The synthesis of thyroid hormones is regulated through a
central feedback system.

Under the stimulatory influence of the

hypothalamic tripeptide thyrotropin-releasing hormone (TRH) also


known as thyrotropin-releasing factor, the pituitary thyrotrophs
secrete TSH. TSH stimulate production of T4 by the thyroid gland.
The circulating T4 and T3 feed back at the level of the pituitary and
the hypothalamus to regulate the release of (TSH) (66). Decrease in
plasma T4 results in increased release of TSH, stimulating the thyroid
gland to secrete more hormone(68). Decreased T4 secretion or
increased conversion of T4 to T3 influence the overall secretion of
TSH(69).
1.8.3.1. Neural control of pituitary-thyroid function:

The nervous system plays a major role in the regulation of


the pituitary-thyroid axis. All the secretions of the anterior pituitary
gland, are under the neural control of the hypothalamus hormones
(releasing factors). Regulation of TSH secretion by the hypothalamus
is through TRH, which is one other neuro-endocrine control
mechanisms of anterior pituitary gland(70).

1.8.3.2. Auto-regulation of the thyroid gland:


The thyroid gland can regulate its own function independent
of TSH by the mechanism known as autoregulation, which is the
capability of the gland to modulate its own function as an adaptive
mechanism to changes in the environment(71). Autoregulaiton is
involved in nearly every step of the intrathyroidal iodine metabolism.
It has been reported that the transport of iodine through the
membrane of the thyroid gland, the organic binding of iodine, the
generation of monoiodotyrosine (MID) and diiodotyrosine (DIT), the
secretion of thyroid hormone and the size of and histological structure
of thyroid gland, all these steps depend on each other and not only
on TSH(71,72).
1.8.4. Hormone synthesis:

Thyroid hormones synthesis begins when circulating iodine is


trapped by the iodine pump and undergoes orgnification by
thyroglobulin, resulting in the formation of MID and DIT, which
condense to form T3 and T4 that are stored in thyrogloibulin molecule
in the form of colloid or are released into the circulation.
Thyroglobulin itselt not released into the plasma and ingested
in the colloid by the thyroid cells(66,73).
1.8.5. Hormone degradation:
Thyroid hormones are catabolised by deiodination in the liver,
kidney and many other tissues. One third of the circulating T4 is
normally converted to T3 and 40% to reverse T3 (rT3),(73) a third
hormone which is synthesized by a different deiodinase from that
which produce T3, its physiologic role is unknown(66,73).

T3 and rT3

are then converted to various diiodothyronines.(66)


1.8.6. Hormone transport:
T4 and T3 are transported in the plasma bound to the thyroid
hormone-binding proteins TBG the major binding protein (70%) and
thyroxin-binding prealbumin. Albumin also bind to thyroid hormones
with low affinity. The protein pound fractions of circulating T4 and T3
account for more than 99% of the total hormone. Minor changes in

the level of TBG can result in a significant change in the level of total
circulating hormone, although the free (i.e. metabolically available,
not protein pound) hormone remain the same. For the same reason,
TBG acts as a buffer to protect the tissues from fluctuations in T4
levels. Disorder of TBG have been described(66).

1.8.7. Cellular effect:


After entering cells T3 and to lesser degree T4 bind to alpha
and beta-receptors in the nuclei, binds to DNA trigger the production
of various enzymes that alter cell function(73).

Thyroid hormones

increase the activity of membrane-bound Na-K ATPase in many


tissues. The physiologic effects of thyroid hormone are protean,
accounting for the myriad symptoms that occur in thyroid disorder.
These effects include effects on the maturation of the central nervous
system (CNS) and skeleton, maintenance of oxidative metabolism
and heat production, and maintenance of cardiovascular function.
The circulating levels of thyroid hormone also affect muscle tone,
deep tendon reflexes and maturation of the epidermis(66).
1.8.8. Thyroid function tests (TF) test:(66)

1.8.8.1. Static test: include measurement of plasma levels of the


various components of thyroid system.
Total T4 concentration is determined by an immunometric
assay that is the widely used test of TF and reflects the total of
the protein-bound and free hormone, free T4 also is measured
immunometrically.
Total and free T4 are determined using the same
methods. In normal individuals, two thirds of the T3 measured
in plasma arises from peripheral deiodination of T4, and only
one third arises from direct secretion from the thyroid gland.
The T3 resin uptake (T3RU) estimate the number of
thyroid hormone-binding protein sites, reflecting the circulating
level of T4.
TSH levels determined by an ultrasensitive immunometric
assay and are helpful in the interpretation of thyroid hormone
levels.
Measurement of TBG levels now is widely available, and
this information is useful for interpreting abnormal thyroid
hormone levels.

Immunoglobulin measurement helpful in the diagnosis of


thyroid disorder which may present in autoimmune disorder of
the gland.
1.8.8.2. Dynamic tests:
The TRH stimulation test of TSH release is a helpful tool
in the evaluation of patients whose thyroid hormone and TSH
levels do not establish a diagnosis.
The T3 suppression test is helpful in differentiating
hyperthyrolidism caused by autonomous gland hyper function
from other causes.
1.8.8.3. Radiologic studies:
It involves the administration of radioactive isotope, which are
taken by the thyroid gland which is higher in infant and children and
because of the risk of radiation it should be minimized in children and
infants.

1.8.9. Abnormal thyroid functions:


Altered

thyroid

hyperthyroidism.(66)
1.8.9.1. Hypothyroidism:

functions

may

be

hypothyroidism

or

Is defined as state in which the thyroid gland fails to secrete


sufficient quantities of thyroid hormone. It is either:
I.

Primary hypothyroidism result from a problem inherent to


the gland itself.

II.

Secondary or central hypothyroidism: result from the


failure of pituitary stimulation of the thyroid gland.
Primary and secondary hypothyroidism can be either
congenital or acquired.(66)
1.8.9.1.1. Congenital hypothyroidism (CHT):
Can either be due to aplasia, hypoplasia (the most common
causes), radioiodine effect, thyrotropin deficiency, thyroid hormone
unresponsiveness and defective synthesis of thyroxine.(66,68)
CHT is diagnosed only rarely from clinical abnormalities most
cases are detected as a result of newborn screening tests. Signs and
symptoms of congenital hypothroidism are listed in table 1.1 below.(66)

Table (1.1): signs and symptoms of CHT


Large fontanels

Prolonged jaundice

Umbilical hernia

Constipation

Macroglosia

Lethargy

Mottled dry skin

Difficulty feeding

Hypotonia

Hypothermia

Abdominal distension

Sleep through the night

Hoarse cry

Goiter

Respiratory distress

Functional abnormalities may occur in 1-2% of newborn


infants and are most common in premature infants.(69) In Sudan the
incidence was found to be 1%.(74) Females are affected more than
males.(66)
1.8.9.1.2. Acquired hypothyroidism (AHT):(66)
The most common causes are:
I.

Thyroiditis (Hashimo thyroiditis).

II.

Autoimmune thyroiditis.
Central acquired hypothyroidism is caused by pituitary or
hypothalamus dysfunction. Symptoms and signs of AHT are listed in
table (1.2) below:
Table (1.2): signs and symptoms of AHT
Short stature

Lethargy and tiredness

Obesity

Delay reflexes

Goiter

Bradycardia

Cold intolerance

Delayed puberty

Constipation

Precocious puberty (rare)

Dry cool skin

Dry thin hair

Loss of memory

Screening for hypothyroidisms involves T4 and TSH and


some doctors include measurement of T3 as well. Typically in
hypothyroidism T4 and T3 be low and TSH will be elevated.
1.8.9.2. Compensated hypothyroidism:
Some infants and young children have blood test that show
normal T4 but a high TSH, this condition is also called idiopathic
hyperthyrotropinemia or subclinical hypothroidism. While the cause
isn't clear, this may reflect regulatory defect of TSH, or it may be a
sing of impending true hypothyroidism.(75,76)
1.8.9.3. Hyperthyroidism:
Occurs when excessive amount of circulating thyroid
hormone is present. It is either congenital or (neonatal thyrotoxicosis)

or acquired, which is most often caused by Graves disease (i.e.


autoimmune thyrotoxicosis), it is more in females.(66)
Signs and symptoms of hyperthyroidism are listed in table
(1.3) below.

Table (1.3): Signs and symptoms of hyperthyroidism:


Goitre
Nervousness (restlessness)
Tachycardia, wide pulse pressure.
Increased appetite.
Weight loss or gain.
Tremor.
Heat intolerance, sweating.
Diarrhoea.
Fatigue
Sleep disturbances.(66)

1.8.10. Management of thyroid disorder:


1.8.10.1. Hypothyroidism: is treated with thyroxine replacement and
usually needed for life. With treatment children with CHT will have
normal somatic and intellectual growth and development, if left
untreated severe mental retardation and neurologic dysfunction
ensure. Improvement is seen in physical symptoms
hair(78)

improvement

in

cognitive

(77)

re-growth of

functioning(79)and

social

functioning.(20)
1.8.10.2. Hyperthyroidism: is treated with measures to reduce
thyroxine activity, medically with carbimazole, propylthyiouracil or
radioactive

iodine,

while

surgical

intervention

involve

partial

thyroidectomy.(80,81)
1.8.10.3. Subclinical hypothyroidism: treatment of subclinical
hypothyroidism is contraversal see under management in DS.

1.9. Down syndrome and thyroid disturbances:


It is well recognized that thyroid dysfunction occurs more
frequently in DS than in general population.(20)
1.9.1. Prevalence studies:
Over the last 30 years many publications have suggested an
association between DS and thyroid disorder by showing altered

levels of T4, T3 & TSH.(82) There is a wide variation in reported


prevalence of thyroid disorder in the DS population. Differences can
be accounted for by the variability in the definitions of the thyroid
disorder employed in different studies, by the different populations
(size, age) studied, and to the type and extend of thyroid dysfunction
measured thyroid autoantibody status, TSH concentration, and T4 or
FT4 concentrations and by different techniques used to measure
given hormones and antibodies (See table 1.4).(20,82)
Table (1.4): Some of studies of prevalence of children with DS
and thyroid disorder
Author (Ref.)

Year

No. of

Age range

sub. in

year

M/F

study

No. of

Abnormality

patients

in one or

with thyroid

more of

dysfunction

values of
TSH, T4, T3 %

Pearse et al

1963

151

6-21

25

17

Samuel et al

1981

54

9-12 day

20/34

10

18

Fort et al

1984

1130

3-16 day

12

1.0

Ziai et al

1984

62

5-16

40/22

11

Coleman

& 1984

206

<18

16

& 1985

151

3-21

92/59

41

27

Abassi
Pueschel

Pezzullo
Cutler et al

1986

49

4/12 -3

24/25

18

37

Toledo et al

1997

105

3/12 - 20

50/55

54

51

Jaruratansiri-

1998

112

<1

17

15

kul et al

Modified from Prasher VP(1999).


Most studies reported a prevalence rate higher than that in
the general population.(82)
1.9.1.1. Congenital hypothyroidism (CH):
A large study of CH in neonates with DS reported a
prevalence of 0.12%; twenty-eight times greater than for the general
population.(83) There is an unexplained higher incidence of CH(84)
detected by T4 - based neonatal screening programs and a very high
prevalence of (mild) plasma TSH elevation in young children with DS
(4-10 m/u/liter), up to 100% during their first 6 months of
life,(58,85,86,87,88,89) that decreases with age. Since 1980s, research on
the clinical significance of this mild TSH elevation has focused mainly
on effects on childhood growth with conflicting results.(58,86,90)
However, the most important question is whether the TSH elevation
reflects mild hypothyroidism that could harm brain growth and

development in the youngest children with DS and contribute to the


ever-present mental retardation.(91) An offer-used argument against
this hypothesis is the finding that accompanying plasma thyroid
hormone concentrations generally are within the age-specific normal
range.(75,86) However, most of these studies derived from studies in
older children with (DS).(58,75,86) Essentially all persons with DS have a
thyroid (regulation) disorder that may give rise to subobtimal plasma
thyroid hormone concentrations at least during infancy.(84)
1.9.1.2. Acquired hypothyroidism:
A general estimated incidence of all types of thyroid disease
in DS falls in the range of 13-63% with hypothyroidism 13-54%.(11)
Autoimmune

process

account

for

much

of

the

acquired

hypothyroidism pathology. Antithyroglobulin and anti-microsomal


antibodies can be very helpful in predicting outcomes of abnormal
thyroid function tests observed in screening programs. However, the
predictive value is not complete. Not all individuals with positive
antibodies express thyroid failure, and not all with hypothyroidism
have detectable antibodies.(76)
The prevalence of acquired thyroid disorder increases with
age, with higher rates being found in older persons with DS.(77,92,93,94)

As well as an increase in the prevalence of hormonal abnormalities


there is also an increased prevalence of autoimmune thyroiditis.
Coleman and Abassi (1984)(95) found lymphocytic thyroiditis in 15 of
16 patients. Ivarsson, et al (1997)(96) found 39% of their sample of 70
children positive for thyroid antibodies. Ali, et al(97) found in 58 Kuwaiti
subjects with DS thyroid disorder of 55% (15.5% had primary
hypothyroidism,
secondary

32.7%

had

hypothyroidism,

subclinical
1.7%

hypothyroidism,

hyperthyroidism

and

1.7%
1.7%

subclinical hyperthyroidism. Antithyroid antibodies were found in 52%


of the total subjects and in 59% of these with thyroid dysfunction.
1.9.1.2.1. Clinical features:
Clearly it is desirable to detect hypothyroidism as early as
possible in any individual, and especially in children who already
have growth impairment and learning disability, however, clinical
diagnosis is difficult in DS. The hypothyroidism features can be
masked by te phenotypic appearance, and symptoms such as weight
gain, poor growth, and dulling of affect might be attributed to the
syndrome itself. Conversely symptoms such as weight-gain and cold
intolerance might be attributed to hypothyroidism in individual with DS
who have only marginally raised TSH values and low normal T4

concentrations.(20) Persons with DS are usually shorter in height,


appears less active, has dry skin and fine hair, excess weight gain,
bradycardia and mental retardation, these features are seen in
hypothyroidism(82) (see clinical features of DS and table 1.2). It is
more difficult to pick up symptoms of hypothyroidism in infants, they
include decreased growth and development, an enlarged tongue,
decreased muscle tone, dry skin and constipation, all of which might
be expected in an infant with DS (see clinical features of DS and
Table 1.1). However, prolongation of physiological icterus, feeding
difficulties, sluggishness, lack of interests, somnolescence and
chocking spells during

nursing could be present during the first

month. Respiratory problems due to large tongue, episodes of


apnoea, noisy respiration and nasal obstruction could point towards a
hypothyroid state in older infants.(82)
Affected infants cry little, sleep more, have poor appetite and
show general sluggishness. Presence of an umbilical hernia,
subnormal temperature and slow pulse point to the diagnosis of
hypothyroidism in children with DS,(98) by age of 6 months the clinical
diagnosis may be easier. Older children may show growth
retardation,(82) but Mani (1988)(99) and Prasher (1995)(62) found a poor

correlation

between

clinical

hypothyroidism

and

biochemical

hypothyroidism.
1.9.1.3. Hyperthyroidism:
Hyperthyroidism

occurs

much

less

frequently

than

hypothyroidism. The reported ranges of frequencies is 0.87 -2.5%.


The symptoms complex shows less overlap with typical DS features,
but there can still be confusion.(76)
1.9.2. Other conditions possibly associated with DS and thyroid
disorders:
Other abnormalities may suggest the presence of a thyroid
disorder,

e.g.

abnormal

electrocardiogram

consistent

with

hypothyroidism,(100) presence of a goitre,(101) detection of pericardial


effusion,(102) dementia,(79) detection of alopecia areata,(103) premature
puberty.(104)
Others have studied the role of trace elements on the
aetiology of thyroid dysfunction in DS. Napolitano, et al (1990)(105)
and Licastro et al (1992)(106) have suggested that zinc deficiency may
be a cause of thyroid disorder in DS.
1.9.3. Treatment of thyroid disorder in DS:

Treatment of frank hypo- and hyper-thyroid conditions in


people with DS follow standard therapeutic recommendations.
Controversy remains regarding the management of subclinical
hypothyroidism. Recent studies of thyroid dysfunction in the DS
population (Rubello, et al, 1995)(75) suggest that subclinical
hypothyroidism is a common transient condition in people with DS.
Selikowitz (1993)(107) in a 5 years longitudinal study of 101
children, 8 children developed subclinical hypothyroidism, which in
half resolved spontaneously at the end of the study period.
Rubello et al (1995)(75) found that in the presence of thyroid
autoimmunity, a subclinical hypo- or hyper-thyroidism can developed
in definite hypo-or hyper-thyroidism. In individual with absence of
thyroid autoimmunity spontaneously normalization of TSH levels can
occur. If symptoms attributed to thyroid disease are seen in such
cases treatment with thyroid hormone may be indicated.(91)
Appreciable benefit following treatment of subclinical hypothyroidism
with

thyroid

hormone

supplementation

remains

in

doubt.(108)

Researchers failed to show any efficacy of short-term thyroid


hormone therapy for population with subclinical hypothyroidism as
assessed in a double-blind cross-over drug placebo trial.(82)

JUSTIFICATION

1-

Thyroid disorders are common problems in children with DS,


and many studies have explored that relationship but in a wide
range of frequencies and prevalence.

2-

Clinical diagnosis of thyroid disorders is difficult in DS, that the


signs and symptoms of thyroid disorders are difficult to pick up in
children with DS.

3-

Early detection and treatment of thyroid disorders may limit their


effect. Clearly, it is desirable to detect hypothyroidism as early as
possible in any individual, and especially in children who already
have growth retardation.

4-

There is no routine screening for thyroid dysfunctions in


newborns in Sudan.

5-

Not a single thyroid study in children with DS was done in


Sudan.

OBJECTIVES

1-

To determine the frequency rate of common types of thyroid


diseases in children with DS in Khartoum State.

2-

To look for possible associated conditions in children with DS


and thyroid diseases.

PATIENTS AND METHODS


2.1. Study design: Descriptive, cross-sectional facility-based study.
2.2. Study area: Seven of institutes and schools for children with
special needs and handicapped in Khartoum State.
i.

Sakina Institute, Elmawrada, Omdurman


City.

ii.

Eltagwa

Institute,

Elthawra

18,

Omdurman City.
iii.

Fersan El-erada Institute, Khartoum 2,


Khartoum City.

iv.

Modern Children Institute, Khartoum 2,


Khartoum City.

v.

Aaisha Institute, Hay El Zihoor, Khartoum


City.

vi.

Basma Institute, Amarat St. 62, Khartoum


City.

vii.

Al-Erada School, Mogran, Khartoum City.


and most of the hospital in the State:

i.

Khartoum Children Emergency Hospital.

ii.

Khartoum Teaching Hospital.

iii.

Mohamed Alamin Hamid Children Hospital,


Omdurman.

iv.

Khartoum North Teaching Hospital.

v.

Ahmed Gasim Children Hospital.

vi.

Alban

Jadid

Hospital,

Elhaj

Yousif,

Khartoum North.

2.3. Study duration: Data were collected in the period from 1st of
April 2002 to 31st of March 2003.

2.4. Study population: All children with DS, attending outpatient


clinics or resident in the above mentioned hospitals or attending
schools or institutes mentioned above during the study period.
2.5. Case definition: Cases are diagnosed clinically according to
principal clinical features in newborns and features of DS.
2.6. Inclusion criteria:Children from birth up to 16 years old,
presenting with clinical features of DS.
2.7. Exclusion criteria:
1.

Children whose parents or care takers refuse


to be enrolled in the study.

2.

Children already on any treatment for thyroid


diseases.
2.8. Sample:

2.8.1. Size: The minimum sample size was 96 calculated according


to the equation:
N = Z2 Pq def

= (1.96)2 0.5 0.5 1

d2

(0.1)2

Where:
N = sample size.
Z = statistical certainty (1.96 at 95%, level of confidence).
P = Probability of success.

q = Probability of failure (1- p).


d = desired margin of error.
Def = design effect.
2.8.2. Design: Venous blood sample was taken from every child with
DS attending the mentioned institutes and hospitals. Blood
analyzed for T4, T3 and TSH.
2.9. Study technique:
2.9.1. Consent: Verbal consent was obtained from parents or care
takers.
2.9.2. Research team: The research team was composed of:
1-

Author.

2. Laboratory

technician.
2.9.3. Input of the author:
Input of the author was to:
1.

Designs study and questionnaire.

2.

Make necessary contacts and permissions.

3.

Conduct full physical examination of the


children.

4.

Collect the blood samples, which was analysed


by the laboratory technician.

5.

Visits school, institutes and hospitals.


2.9.4. Research tools:
2.9.4.1. Data collection technique:
Questionnaire included personal data and history, past
medical history, family history, nutrition history and drugs, address
and phone number was completed for all study subjects.
Informations obtained on the pregnancy (gestational age,
history of irradiation, history of drugs), neonatal period (neonatal
jaundice, suckling), child's condition around his early and late
childhood

(recurrent

infections,

other

diseases,

and

medical

investigations and procedures performed during that period) and


special attention was put on signs and sumptoms of thyroid disorder.
Data were collected by interviewing parents or care takers in
addition to hospital and institutes records.
General

examinations

and

clinical

assessment

were

obtained. For children whom consent had been given venous blood
was obtained. Height and weight of the study children were compared
to the American centiles.(109)
2.9.4.2. Laboratory tests:

Five milliliters of blood were collected and left at room


temperature for two hours, following centrifugation serum was
aspirated and stored at -20C for the determination of T4, T3 and TSH
levels.
Materials:
1. Anti T4 coated beads.
2. Anti TSH coated beads.
3. Anti T3 coated beads.
4. buffers:
a.

Buffer PBSX- 25-mM phosphate.

b. IRMA assay

buffer.
c. Wash buffer.
d. Tracer solution I -125 monoclonal anti TSH.
e. Standards.

f. Coated beads.

g. RIA tracer's buffer.

h. Tracer solution I -125 -T4.

Methods:
T4: sufficient test tubes were labelled in duplicate for the
standard set quality control pools and the samples. 10 l of
standard, quality control and sample were pipetted into the
corresponding tubes, 200 l of T4 tracer were added, mixed,

one bead was added to each tube and tubes were added to
each tube and aspirated, washing step was repeated twice and
the beads were counted in the gamma counter for 100 seconds.
The same steps were done to TSH and T3 tests.
2.10. Data entry and statistical methods:
The data obtained from the questionnaire was entered into
the computer and analysed using Statistical Package Social Sciences
(SPSS), chi-square was used to 95% significant level.
2.11. Budget: The author without external funds financed this
research.
2.12. Encountered difficulties: The anticipated difficulties in doing
this study were the difficulties in attempted venous sampling,
we found venepuncture is difficult to perform in some cases,
but the uptake of screening in the study has been excellent,
that no patient was unscreened. Other things which needed
more effort was to convince families of children about
importance of screening. These problems had been resolved
and at the end all of them accepted to be enrolled in the study.
2.13. Ethical points:

Children found to have thyroid diseases were referred for


further investigations and treatment.

RESULTS
A total of 96 children with DS were enrolled in this study.
They included 55 boys and 41 girls aged less than 16 years for whom
clinical data were obtained, and they were investigated for thyroid
function.

3.1. Socio-demographic characteristic:


3.1.1. Age and sex characteristic of the study:
The mean (SD) ages of children in the study was 84.2 (70.4)
months. Regarding sex characteristic, males were 55(57.3%), while
females were 41(42.7%), male to female ratio was 1:1.34 (Fig. 3.1).
3.1.2. Description of the social status of the study group:
Figure 3.2 shows the social status of the children in the
study, most of them were of moderate social class 46(47.9%)
children, followed by those of low social class 39(40.6%) children,
and only 11(11.5%) children were of high social class.
3.1.3. Mother's age at the time of conception:
Mother's age group (15-29 years) were 24(25%) mothers,
14(14.6%) mothers were in the age group (30-34 years), 39.6% of

mothers were below 35 years of age at the time of conception, 60.1%


of mothers their ages more than 35 years, 29(30.2%) were in the age
group (35-39 years), 27(28.1%) mothers in the age group (40-45) and
one (1%) mother was above 45 years of age at the time of conception
(Table 3.1).
3.1.4. Fathers' age (in years) at time of conception:
Table 3.2 shows fathers' age of the study group at the
conception. Fathers in the age group (25-29 years) were 3(3.1%), in
the age group (30-34 years) were 10(10.4%), in age group (35 -39
years) were 23 (24%), in the age group (40-44 years) were
21(21.9%), in the age group (45-49 years) were 19(19.8%) and 20
(20.8%) were in the age more than 50 years.
3.1.5. Child education:
Fifty-one (53.1%) children were educated in rehabilitation
institutes, 1(1%) child was educated in Basic school and there was no
education for 44(44.9%) children (Fig. 3.3)
3.1.6. Fathers' education:
The predominant group were those educated to the
secondary level 47(49%) fathers, followed by university level

22(22.9%), primary level 12(12.5%), post graduated were 9(9.4%)


and only 6 (6.3%) fathers were illiterate (Table 3.3).

3.1.7. Mothers' education:


Most of the mothers educated to secondary level, 44(45.8%),
followed by primary level 26(27.1%), university graduated mother
were 18(18.8%), one (1%) mother was postgraduate and 7 mothers
(7.4%) were illiterate (Table 3.4).
3.1.8. Fathers' occupation:
The majority of fathers were governmental employee
33(34.4%), followed by businessmen 23(24%), skilled labourer
14(14.6%), professional were 13(13.5%), unskilled labourer were
11(11.5%) and unemployed were two (2.1%) (Table 3.5).
3.1.9. Mothers' occupation:
The majority of mothers were housewives 75(78.1%),
followed by governmental employee 11(11.5%), professional 5(5.2%),
unskilled labourer 3(3.1%), skilled labourer two (2.1%) (Table 3.6).
3.1.10. Parent consanguinity:
Figure 3.4 shows the parent's consanguinity of the children in
the study. Parents of 18 (18.8%) children were first-degree cousin, as

well as second-degree cousins. Third degree cousins were


16(16.7%) and not related parents were 44(45.8%).

3.1.11. Childbirth order:


Childbirth order of children in the study showed in Table 3.7.
3.1.12. Number of sibs:
Number of sibs of children in the study showed in Table 3.8.
3.1.13. Number of abnormal sibs (dysmorphic or retarded):
Only two (2.1%) children had one abnormal sibs and one
(1%) child had two abnormal sibs.
3.1.14. Family history of abnormal members (dysmorphic or retarded):
Positive family history of abnormal members was found in
11(11.5%) children.
3.1.15. Gestation age for children in the study:
Table 3.9 shows that, the largest number of children were
delivered at full term gestational age 79(82.3%), 13(13.5%) were
preterm, and 4 (4.2%) were post term.
3.1.16. History of irradiation during pregnancy:
History of irradiation was positive in only 6(6.3%) children.
3.1.17. Weight centile for children in the study:

Weight centile for the study group was shown in Fig. 3.5.
3.1.18. Height centile for children in the study:
Height centile for the study group was shown in Fig. 3.6.

3.2. Frequencies of common symptoms of thyroid


disorder in DS in the study group:
The common symptoms of thyroid disorder among the
children in the study were hypotonia in 90(93.8%) children, Heat
intolerance

in

40(41.7%),

constipation

in

23(24%),

tiredness

21(21.9%), dry skin in 20(20.8%) umbilical hernia in 19(19.8%),


irritability in 18(18.8%), prolonged neonatal jaundice in 15(15.8%),
change in mood in 10(10.4%), cold intolerance in 9(9.4%) and loss of
memory in 7(7.3%), diarrhoea in 6(6.3%) (Table 3.10).

3.3. Associated conditions:


Regarding associated conditions, children with known cardiac
disease were 25(26%), those with loss of or impaired memory were
8(8.3%), associated nystgmus were 5(5.2%), cataract in 3(3.1%),
squint in 2(2.1%), alopecia in 2(2.1%), one (1%) child had one
kidney, one (1%) child had undescended testes and one (1%) had
impaired vision.

3.4. Clinical pattern of thyroid disturbances:


3.4.1. Types of thyroid disorder in the study group:
Ninety-six children were investigated for thyroid function,
58(60.5%) children were found to have normal thyroid function.
Thyroid

diseases

were

found

in

the

remaining

38(39.5%).

Hypothyroidism was detected in 20(20.8%) children, two of them


were neonates ages 6 and 7 days (congenital hypothyroidism),
hyperthyroidism was detected in one (1%) child and subclinical
hypothyroidism was detected in 17 of the patients (Fig. 3.7).

3.4.2. TSH levels:


Table 3.11 shows TSH and T4 levels in comparison with age
specific TSH was in the normal range to age in 58(80.5%) children,
low in one (1%) child and high in 37(38.5%) children, those with high
TSH levels were in two groups. The first group is those with high TSH
levels and normal T4 and T3 levels (compensated hypothyroidism),
they were 17 children, for this group TSH ranges frequencies shown
in (Table 3.12). The second groups were those with high TSH levels
and low T4 levels (hypothyroidism) they were 20(20.8%), for this

group, frequencies to TSH ranges were shown in (Table 3.13) mean


TSH (SD) was 5.5 (3.0) u/ml.

3.4.3. T4 levels:
Table 3.14 shows T4 levels in the study group compared to
the age specific range. T4 (SD) was 87.6 (29.4) u/ml.

3.4.4. T3 levels:
Table 3.15 shows T3 levels in the study group compared to
the age specific range. T3 (SD) was 1.2 ( 0.4) u/ml.

3.4.5. Age and thyroid disturbances:


TSH status in different age groups was shown in Table 3.16,
and T4 status in Table 3.17. Congenital hypothyroidism was detected
in two (2.1%) neonates age 6and 7 days, 6(6.3%) children in age
group (two months ->one year), 5(5.3%) in age group (1- <5 years),
3(3.1%) in age group (5-<10 years) and 4(4.2%) children in the age
group (10-16 years) compensated hypothyroidism was detected in
two (2.1%) in age < 2 months, 5 (5.3%) in the age group (1-<5 years),
5(5.2%) in the age group (1->5 years), 5(5.2%) children in the age
group (5-<10 years) and 7(&.3%) children in the age group (10-16
years).

Hyperthyroidism was found in one child in the age group


(1-<5 years) (P. = 0.093).

3.4.6. Sex and thyroid disturbances:


Table 3.18 shows thyroid disturbances in relation to sex
among the study children, 12(21.1%) of males were found to have
hypothyroidism, while females were 8(19.5%), one (2.4%) female had
hyperthyroidism,

10(18.2%)

of

males

were

found

to

have

compensated hypothyroidism and 7(7.1%) females were found to


have compensated hypothyroidism (P = 0.462).
3.4.7. Common symptoms of thyroid disorders in DS found
in children with thyroid disturbances in the study:
Concerning common symptoms of thyroid disorders found in
the children of the study, change in mood was found in 10 children,
no one of them had hypothyroidism and 7 of them were found to have
normal thyroid function and one child with hyperthyroidism (P = 0.01).
Loss of memory in 7 children, 4 with normal thyroid function and 3
with compensated hypothyroidism. Irritability in 18 children, two with
hypothyroidism, 13 with normal thyroid function and 3 with
compensated hypothyroidism (P = 0.624). Tiredness in 21 children,

four with hypothyroidism, 12 with normal thyroid function, one with


hypothyroidism and 4 children with compensated hypothyroidism
(P= 0.297). Heat intolerance in 4 children with hypothyroidism, 26
children with normal thyroid function, and one with hyperthyroidism
and in 9 children with compensated hypothyroidism (P= 0.94). Cold
intolerance was found in 9 children, 2 with hypothyroidism, 3 with
normal thyroid function and 4 with compensated hypothyroidism
(P =0.149).
Bowel habits was found as follows: constipation in 7 children
with hypothyroidism and 11 with normal thyroid function in 5 children
with compensated hypothyroidism. Diarrhoea in one patients with
hypothyroidism and in five children with normal thyroid function
(P = 0.645) (Table 3.19).
Neonatal jaundice was found in the 2 neonates with
hypothyroidism, history of neonatal jaundice was found in 15 children,
9 of them had hypothyroidism and 6 had normal thyroid function.
Large anterior fontanel was found in most of the children below 2
years of age, 16 with normal thyroid function and 19 with
hypothyroidism. Umbilical hernia was found in 19 children, 9 of them
had normal thyroid function (Table 3.19).

3.4.8. Associated condition among children with thyroid


disturbances in the study group:
Table

3.20

shows

associated

condition

with

thyroid

disturbances in children of the study, 12(50%) children with known


congenital heart disease was found had thyroid disturbances.
Diabetic mellitus in one child who was found had hypothyroidism.
Alopecia in two children, both had hypothroidism, one child with
urinary tract malformation had compensated hypothyroidism. One
child with goitre had hypothyroidism, 3 children with cataract one of
them had compensated hypothyroidism. Mother of one child had
hypothyroidism and she on thyroxine therapy, her DS child was found
to had normal thyroid function.

Fig. 3.1 Age and sex distribution of the study group


24
25

No. of children

20

17

Male
Female

15

12
11

10

10
5

6
3

7
3

0
0-<2 month

2 month - <1y ear

1-<5 y ear

5-<10 y ear

10-16 y ear

Age group

P = 0.766

Fig. 3.2: Distribution of the study group


according to the social status

High
11(11.5%)
Low
39(40.6%)

Moderate
46(47.9%)

Fig.3.3: Child education distribution of


the study group

1(1%)

44(45.80%)
51(53.20%)

Fig. 4: Distribution of study group according to


parent's consanguinity

First degree
18(18.8%)

Not related
44(45.8%)

Second degree
18(18.8%)

Third degree
16(16.7%)

Fig. 3.5: Distribution of children in the study according


to weight centile

30

26

No. of children with DS

25

22

22

18

20
13
15
10
5

0
< 3rd

3rd - <5th

5th - < 25th

25th -< 50th

50th -<75th

75th - <95th

>95th

Weight (centile)

Fig. 6: Distribution of children in the study according


to height centile
33

No. of children with DS

35
30
25
20
15

12

12

15

12

10

10
5
0
3rd - <5th

5th - < 25th

25th -< 50th

50th -<75th

Height centile

75th - <95th

>95th

Fig. 3.7: Distribution of the study group according


to thyroid status

Hypothyroidism
20(20.8%)

Normal thyroid
function
58(60.4%)

Compensated
hypothyroidism
17(17.7%)
Hyperthyroidism
1(1%)

Table 3.1: Distribution of mothers' age at time of conceptions


of the study group
Age group (in years)

Frequency

Percentage

Cumulative percentage

15 - 29

24

25%

25%

30 - 34

14

14.6%

39.6%

35 - 39

29

30.3%

69.8%

40 - 45

28

29.2%

99%

> 45

1.0%

100%

Total

96

100%

100%

Table 3.2: Distribution of fathers' age at time of conceptions


of the study group
Age group (in years)

Frequency

Percentage

25 - 30

3.1%

30 - 34

10

10.5%

35 - 39

23

24%

40 - 44

21

21.9%

45- 49

19

19.8%

50 - 55

20

20.8%

Total

96

100%

Table 3.3: Distribution of the study group according


to fathers' education

Educational level

Frequency

Percentage

Illiterate

6.3%

Primary

12

12.5%

Secondary

47

49%

University

22

22.9%

Postgraduate

9.4%

Total

96

100%

Table 3.4: Distribution of the study group according


to mothers' education

Educational level

Frequency

Percentage

Illiterate

7.3%

Primary

26

27.1%

Secondary

44

45.8%

University

18

18.8%

Postgraduate

1.0%

Total

96

100%

Table 3.5: Distribution of the study group according


to fathers' occupation

Occupation

Frequency

Percentage

Professional

13

13.5%

Businessman

23

24%

Governmental employee

33

34.4%

Skilled labourer

14

14.6%

Unskilled labourer

11

11.5%

Unemployed

2.1%

Total

96

100%

Table 3.6: Distribution of the study group according


to mothers' occupation
Occupation

Frequency

Percentage

Professional

5.2%

Governmental employee

11

11.5%

Skilled labourer

2.1%

Unskilled labourer

3.1%

Housewives

75

78.1%

Total

96

100%

Table 3.7: Distribution of birth order in the study group


Birth order

Frequency

Percentage

16

16.7%

10

10.4%

12

12.5%

16

16.7%

11

11.5%

8.3%

52%

9.4%

3.1%

10

3.1%

12

2.1%

13

1.0%

Total

96

100%

Table 3.8: Distribution of number of sibs of children in


the study group

Frequency

Percentage

No sibs

4.2%

1-4

35

36.5%

5 - 10

36

37.5%

> 10

21

21.9%

Total

96

100%

Table 3.9: Distribution of the study group according


to gestational age
Gestational age (in weeks)

Frequency

Percentage

30 - 36

13

13.5%

37 - 40

79

82.3%

42

4.2%

Total

96

100%

Table 3.10: Frequencies of common symptoms of thyroid


disorders in DS in the study children
Symptoms

Frequency

Percentage

Hypotonia

90

93.8%

Heat intolerance

40

41.7%

Constipation

23

24%

Tiredness

21

21.9%

Dry skin

20

20.8%

Umbilical hernia

19

19.8%

Irritability

18

18.8%

Prolonged neonatal jaundice

15

15.8%

Change in mood

10

10.4%

Loss of memory

7.3%

Diarrhoea

6.3%

Total

96

100%

Table 3.11: TSH and T4 levels for the study group compare to
the age specific range

Level

Frequency

Percentage

Normal TSH with normal T4

58

60.5%

High TSH with normal T4

17

17.7%

High TSH with low T4

20

20.8%

Low TSH with high T4

1%

Total

96

100%

Table 3.12: Frequencies of TSH ranges in the study group with


high TSH and normal T4 levels

Range u/ml

Frequency

6 - < 10

13

10 - < 15

15

Total

17

Table 3.13: Frequencies of TSH ranges in the study group with


high TSH and low T4 levels
Range u/ml
4.5 < 10

Frequency
13

10 - < 15

15

Total

20

Table 3.14: Frequencies of T4 levels of the study group


compared to age specific ranges
Level

Frequency

Percentage

Normal

75

78.2%

Low

20

20.8%

High

1%

Total

96

100%

Table 3.15: Frequencies of T3 levels of the study group


compared to age specific ranges
Level
Normal

Frequency

Percentage

66

67.7%

Low

31

32.3%

High

Total

96

100%

Table 3.16: TSH level of the different age groups of


the children in the study
TSH
levels

Age groups
0 -<2 mon. 2 mon.- <1 yr.

1- <5 yr.

5-<10 yrs. 10-16 yrs.

Total

Normal

2 (2.1%)

16 (16.7%)

5(5.2%)

5(5.2%)

30 (24%)

58(52%)

Low

0 (0.0%)

0 (0.0%)

1 (1.0%)

0 (0.0%)

0 (0.0%)

1 (1.0%)

High

4(4.3%)

7(7.4%)

10(10.4%)

5(5.2%)

Total

6(6.3%)

23(24%)

16(16.7%) 10(10.4%) 41(42.7%) 96(100%)

11(11.5%) 37(38.5%)

X2 = 0.938
P. value = 0.905

Table 3.17: T4 level of the different age groups of


the children in the study
T4

Age groups

levels

0 -<2 mon. 2 mon.- <1 yr.

1- <5 yr.

5-<10 yrs. 10-16 yrs.

Total

Normal

4(4.2%)

17(17.2%)

10(10.4%)

7(7.4%)

Low

2(2.1%)

6(6.3%)

5(5.2%)

3(3.1%)

4(4.2%)

20(20.8%)

High

0(0.0%)

0(0.0%)

1(1.0%)

0(0.0%)

0(0.0%)

1(1.0%)

Total

6(6.3%)

23(24%)

X2 = 0.207

37(38.5%) 75(78.2%)

16(16.7%) 10(10.4%) 41(42.7%) 96(100%)

P. value = 0.275

Table 3.18: Thyroid disturbances in relation to sex among


children in the study
Sex

Thyroid status
Male

Female

Total

Normal thyroid function

33 (34.4%)

25(26%)

58(60.4%)

Hypothyroidism

12(12.5%)

8 (8.3%)

20(20.8%)

Hyperthyroidism

0(0.0%)

1(1.0%)

1(1.0%)

Compensated hypothyroidism

10(10.4%)

7(7.3%)

17(17.7%)

Total

55 (57.3%)

41 (42.7%)

96 (100%)

X2 = 0.395

P. value = 0.335

Table 3.19 Horizontal

Table 3.20: Associated condition among children with thyroid


disturbances in the study group
Associated condition

Thyroid

Normal thyroid

disturbance

function

Congenital heart disease

12

13

25

Diabetes mellitus

Alopecia

Urinary tract anomalies

Goitre

Cataract

Total

18

15

33

DISCUSSION
4.1. Frequencies and sociodemographic characters:

Total

Thyroid hormone is important for normal mental and physical


growth,

so

early

detection

of

thyroid

disorder

especially

hypothyroidism is important in any individual, and especially in


children who already have growth impairment and mental deficiency.
However, clinical diagnosis is difficult in DS. This study was carried
out to determine the frequency of thyroid disturbances and
associated conditions in 96 children with DS age less than 16 years,
male to female ration was 1.34 : 1, not differ greatly from the ratio
mentioned previously, 1.15 : 1.(21)
As previously reported this study too found a high frequency
of thyroid disturbances, 38(39.6%) in children with DS (Fig. 3.7).
Previous studies have reported varying rate in children with DS
(13-63%)(11) (Table 1.4).

However, this is the first study, which

investigate thyroid function in children with DS in Sudan and the true


prevalence of thyroid disease in children with Down's syndrome in
Sudan will not be known until screening is continued over a wider
area for a longer period.
In this study hypothyroidism was not significantly related to
sex (Table 3.13) which is not like what was reported by some

researchers that, thyroid diseases are more common in females.(66)


However, this was true for hyperthyroidism.
Regarding thyroid diseases in relation to age, unlike what
was previously mentioned that thyroid diseases tend to increases
with age.

(77,92,93,94)

However, the number was small for accurate

statistical analysis and there was varying numbers of children in each


age group (Table 3.7).
4.2. Clinical pattern:
Hypothyroidism was found to be the most frequent
abnormality evidence in 20(20.8%), this has been reported by many
researcher in the range of (13 - 54).(11) Subclinical hypothyroidism
was detected in 17(17.7%), the incidence of this condition was
reported as 6 - 32.5%.(75,76,107) Also was reported by Ali, et al in
Kuwait as 32.7%. Hyperthyroidism was found to occur very less
frequent (1%), it was found in a female child age one year.
4.3. Clinical symptoms:
This study showed that there was no significant correlation
between clinical symptoms and thyroid disturbances. This was
consistent with the findings of Mani(94) and Prasher( 62) that there is
poor correlation between clinical hypothyroidism and biochemical

hypothyroidism. Symptoms such as change in mood was found in


one patients of hyperthyroidism and 3 patients of subclinical
hypothyroidism at the same time was found in 7 of euthyroid children.
Loss of memory was found in 7 patients, four of them had normal
thyroid function and 3 had subclinical hypothyroidism, it was not
significantly associated with thyroid disturbances. Irritability was also
not significantly associated with thyroid disturbances. It was found in
two patients with hypothyroidism and 13 patients of normal thyroid
function, and three of those with subclinical hypothyroidism.
Surprisingly was not found in the one child with hyperthyroidism.
Tiredness was not found to be significantly associated with
thyroid

disturbances,

it

was

found

in

four

children

with

hypothyroidism, one child with hyperthyroidism and 12 children with


normal thyroid function. Very strangely 41.7% of children with DS in
the study had heat intolerance, the majority of them (65%) had
normal thyroid function, one child with hyperthyrodism was found had
heat intolerance, which goes with the clinical symptoms of
hyperthyroidism in children with Down's syndrome (Table 1.3). Cold
intolerance was not significantly associated with hypothyroidism. It
was found in 3 children with normal thyroid function and 2 of the

children with hypothyroidism and three children with subclinical


hypothyroidism, but it was clearly that it pointed to thyroid
dysfunction.
This study showed that constipation was not significantly
associated with hypothyroidism (Table 2.1), this because constipation
was a known feature in individual with DS. Diarrhoea was not found
in the child with hyperthyroidism. History of neonatal jaundice was not
significantly associated with thyroid disturbances, it was found in six
children with normal thyroid function and nine of those with thyroid
dysfunction. On the other hand, presence of prolonged neonatal
jaundice was significantly associated with hypothyroidism, that both
children with hypothyroidism were had neonatal jaundice. Large
anterior fontanel was found in all children with DS in the study less
than 2 years, 35% of them had hypothyroidism and 65% with normal
thyroid function, because the large anterior fontanel is presenting
signs of Down's syndrome. Umbilical hernia was found in 19.8% of
children in the study, ten of them had thyroid disturbances. This
because umbilical hernia was a presenting feature of Down's
syndrome.

This

showed

that

the

majority

of

symptoms

of

hypothyroidism were not significantly associated with hypothyroidism

in Down's syndrome, this indicate the poor correlation of clinical


hypothyroidism and biochemical hypothyroidism, which is consistent
with the previously mentioned in the literature(94)

and that the

symptoms and signs of hypothyroidism are difficult to pick up in


children with DS.(82)
Symptoms of hyperthyroidism evident in the child with
hyperthyroidism in this study were heat intolerance, tiredness and
change in mood.
4.2.

Associated

condition

in

DS

children

with

thyroid

disturbances in the study group:


An association was found between thyroid disease and CHD
in this study 12 children (50%) with CHD had thyroid disturbances.
Alopecia was found in two children, both had thyroid dysfunction, this
is consistent with what was found by Duviver (1975)(103) The
association of goitre and hypothyroidism in this study was significant,
a similar study showed this association.(101)This study showed that
the presence of diabetes mellitus was strongly associated with
hypothyroidism. It seem both are autoimmune process. Other
association found with genito-urinary tract anomalies (one kidney,
undescended tests).

CONCLUSION
The

study

population

were

children

with

Down's

syndrome below 16 years of age with male to female ratio 1.34


: 1.
Frequency of thyroid disturbances in children with Down's
syndrome was found to be 38(39.6%) with hypothyroidism
20(20.8%), subclinical hypothyroidism was found to be
17(17.7%) and hyperthyroidism was 1(1%).
Thyroid dysfunction was not significantly related to sex.
There was no significant correlation between clinical
symptoms and thyroid dysfunction
There was significant association between hypothyroidism
and neonatal jaundice.
Associated condition in children with Down's syndrome
and thyroid diseases were congenital heart disease, diabetes
mellitus, alopecia, goitre, genitourinary tract anomalies.

RECOMMENDATIONS
Recognizing the increased frequency of thyroid dysfunction in
children with DS and the difficulty in clinical diagnosis, regular
screening for thyroid dysfunction is recommended by TSH and T4
estimation.
Normal thyroid levels are necessary for growth and cognitive
functioning, therefore, early detection of hypothyroidism in any
individual, and especially in children who already have growth
impairment and mental disability is needed, so screening has been
recommended at birth for any newborn with Down's syndrome.
Additional thyroid screening at six months and 12 months should
be performed.
Concerning the increase incidence of thyroid disturbances with
age and the rapid progression of thyroid dysfunction in children
with Down's syndrome suggest that screening should be performed
on an annual basis.
In infants and young children with Down's syndrome a common
transient condition known as idiopathic hyperthyrotropinaemia with
high TSH and normal T4 levels, for these cases repeating the TSH

and T4 every six months, with holding treatment unless the T4 is


low or symptoms attributed to thyroid disease are seen.
The importance of early detection of thyroid disorder needs to be
particularly understood by general practitioner and the junior staff,
therefore, an integrated program should be established by senior
pediatricians to promote both knowledge and skills.
Parents need to be taught about their children condition and the
importance of thyroid screening.
Further studies on thyroid disturbances in children with Down's
syndrome should be conducted to pick up cases of thyroid
disturbances for early detection and treatment and for better
prevalence estimation.

REFERENCES

1-

American Academy of Pediatrics Committee on Genetics.


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