1. Yassin M Y Alsaleh

3. 

subclinical hypothyroidism ,compensated
hypothyrodisim ,mild thyrotropenemia, IRT
isolated thyroropenemia :an elevated TSH
level more than 5 mU/L with normal T3 and
T4 levels.
Overt hypothyrodism,decompensated
hypothyrodism: an elevated TSH level higher
than 10-20 mU/L with low T4 levels.

4. 


down syndrome is the most common
chromosomal anomaly in live births.
incidence of 1:800 live births.
it consists of a constellation of clinical signs
and symptoms as well as biochemical,
metabolic, endocrine dysfunctions.

5. 

Because of medical advances and
improvements in overall medical care, the
median survival of individuals with DS has
increased considerably.
This longer life expectancy requires giving
the necessary care to the individual with DS
over their total longer lifespan.

6. 

Thyroid dysfunction is highly prevalent in
Down's syndrome.
Thyroid disorders have been reported in up
to 28–40% of children with DS, and they
increase in frequency, up to 54%, as the
children age .

7. 


Thyroid abnormalities range:
congenital hypothyroidism (1.8–3.6%) .
primary hypothyroidism, autoimmune
(Hashimoto) thyreoiditis (0.3–1.4%)

Compensated hypothyroidism (25.3–32.9%).

hyperthyroidism(Graves’ disease) (0–2%)

8. 

Patients with DS have an increased prevalence
of both congenital hypothyroidism (CH) and
acquired thyroid dysfunction
incidence of congenital hypothyroidism in
Down syndrome cases is 30 times higher
than that in the general population.

9. 
The clinical symptoms and signs of both
Downs syndrome and hypothyroidism are
overlapping to some extent

10. 

The I.Q. in Down syndrome cases ranges
from 25 – 70 with higher values (50 – 59) in
younger subjects than in the older subjects
(25 – 49) .
Hypothyroidism may compromise the
physical and mental development in patients
with DS.

11. 
The mean D.Q. in the Down syndrome
children with hypothyroidism was 49.5 ± 5.5,
while that in the Down syndrome children
without evidence of thyroid dysfunction was
52 ± 5.54.
Shaw CK, Thapalial A. Thyroid dysfunction in Down syndrome.
Kathmandu University Medical Journal (2006), Vol. 4, No. 2, Issue 14,
182-186

12. •congenital or acquired
•hyper or hypothyroidism
• Compensated or uncompensated
•transient or persistent.

13. 

Subclinical hypothyroidism: Transient mild
TSH elevation is the most commonly seen
thyroid dysfunction in children with DS
The reason is not known and is a common
therapeutic dilemma.
C Henk Konings, A S Paul van Trotsenburg. Plasma thyrotropin
bioactivity in Down's syndrome children with subclinical
hypothyroidism. European Journal of Endocrinology (2001) 144 1±4

14. 

The proposed mechanisim :
could be due to the delayed maturation of the
hypothalamic pituitary axis which in turn
could be due to delayed switching over of the
somatomedines from the foetal to the adult
forms.

15. 
It has been postulated that infants with
transient TSH elevation have a higher
incidence of congenital malformations than
infants with permanent CH
Oakley GA, Muir T. Increased incidence of congenital
malformations in children with transient thyroid-stimulating
hormone elevation on neonatal screening. J Pediatr 1998;132:726730.

16. 
the most common cause of CH in DS is
thyroid dysgenesis.
Devos H, Rodd C, Gagne N, et al. A search for
the possible molecular mechanisms of thyroid
dysgenesis: sex ratios and associated
malformations. J Clin Endocrinol Metab
–
;

17. 

The acquired form of hypothyroidism is
usually associated with thyroid antibodies of
different types and is more common in
children above 8 years.
Autoimmune thyroiditis leading to
hypothyroidism occurring in young children
with Down syndrome
B Karlsson, J Gustafsson,Thyroid dysfunction in
Down’s syndrome:
relation to age and thyroid autoimmunityArch Dis
Child 1998;79:242–245

18. 


Down's syndrome has been linked with other
autoimmune disorders
ex. Alopecia areata and vitiligo ,Diabetes
mellitus, adrenal dysfunction, pernicious
anaemia with chronic active
hepatitis,haemolytic anaemia and gluten
enteropathy
It is thought to be due to a genetically
determined, organ specific defect in
suppressor T-lymphocytes.

19. 

Thyroid antibodies are found in around 30%
of people with Down’s syndrome and have
been detected in children with the syndrome
as early as age 2 years.
The presence of antibodies does not
necessarily imply thyroid dysfunction but
should be taken as an indication to check
thyroxine levels frequently.

20. 
For example, in the NHANES III study in the
US, 13% of the total population had thyroid
peroxidase, and 11.5% had thyroglobulin
antibodies; for the subset of 12–19 year olds
(children under 12 were not included), the
figures were 4.8% and 6.3%, with higher rates
of positivity in females than in males [31].
J. G. Hollowell, N.W. Staehling,W. D. Flanders, et al., “Serum
TSH, T, and thyroid antibodies in theUnited States population
(1988 to 1994): National Health and Nutrition Examination
Survey (NHANES III),” Journal of Clinical Endocrinology and
Metabolism, vol. 87, no. 2, pp. 489–499, 2002.

21. prevention

22. 
Mitchell C (1994) recommended a schedule of
screening Down syndrome patients at 6
weeks 4, 10,16, 24 months and annually
thereafter.
Mitchell C, Blachford J, Carlyle JM.Arch
Pediatr Adolesc Med 1994;148: 441- 442.

23. 
Tuyuz B et al (2001)22 suggested that Down
syndrome patients with normal thyroid
functions and those with compensated
hypothyroidism should be followed annually
and every 3 months.
Tuyuz B and Beker DB.. Thyroid dysfunction
in children Down Syndrome. Acta Pediatrica2001

24. 
Gibson PA et al (2005) suggest initial testing
results could be used as a basis to select a
subgroup for further testing at say five yearly
intervals unless new symptoms emerge
Gibson PA, Newton RW. Longitudinal study of thyroid
function in Down's Syndrome in the first two decades.
Arch Dis Child. 2005 Jun;90(6):557-8.

25. 


the American Academy of Paediatrics,
2001recommended yearly screening.
The incidence of medically treated thyroid
disease in children with Down syndrome in
the TennCare cohort from 1995 to 2005 was
10.8%.
A 73% increase in rate occurred following rerelease of American Academy of Pediatrics
guidelines.
.Kecia N. Carroll, MD, MPH1Increase in Incidence of MedicallyTreated Thyroid Disease in Children with Down Syndrome
Following Re-release of American Academy of Pediatrics Health
Supervision Guidelines. Pediatrics. 2008 August ; 122(2): e493–
e498. doi:10.1542/peds.2007-3252

26. Treatment

27. 
Same as general population.

28. 
the treatment approach to persistent
compensated hypothyrodism is
controversial.
McDermott MT, Ridgway EC. Subclinical hypothyroidism is
mild thyroid failure and should be treated. J Clin Endocrinol
Metab 2001;86:4585-90.
Chu JW, Crapo LM. The treatment of subclinical
hypothyroidism is seldom necessary. J Clin
Endocrinol Metabolisim 2001

29. 
especially in view of the fact that they do not
seem to be associated with abnormal
myocardial structure and function.
Toscano E, Pacileo G, Limongelli G, et al.
Subclinical hypothyroidism and Down’s
syndrome; studies on myocardial
structure and function. Arch Dis Child 2003

30. 
van Trotsenburg et al demonstrated that LT4 replacement for the first two years of life
could improve psychomotor development and
growth in infants with DS
van Trotsenburg AS, Vulsma T. The effect of thyroxine treatment
started in the neonatal period on development and growth of twoyear-old Down syndrome children= a randomized clinical trial. J Clin
Endocrinol Metab 2005;90:3304-3311. Epub 2005 Mar 8

31. 
that subclinical hypothyroidism and lownormal fT4 levels in patients with DS may
have significant clinical sequelae, such as
hypotonia and anemia,
Lebel EW, Tenenbaum A. Low-normal FT4 and subclinical
hypothyroidism may have a detrimental clinical effect in
Down syndrome. Horm Res Paediatr 2011;76(Suppl 2):46-47.

32. 
Scottish Down Syndrome Thyroid Screening
Group recently suggested that most patients
with mildly elevated TSH levels (6-10 mU/L)
do not require treatment but only surveillance
initially.
McGowan S, Jones J,; Scottish Down Syndrome
Thyroid Screening Group. Capillary TSH screening
programme for Down’s syndrome in Scotland,
1997-2009. Arch Dis Child 2011;96:1113-1117. Epub
2011 Sep 30

33. 

Some children with DS demonstrate a
persistently elevated TSH level for at least
several years without developing overt
hypothyroidism, whereas others revert to
normal.
The mean TSH level (45.6 ± 33.4 mU/L)
was statistically significantly higher
Dilek Sarici, Mustafa Ali Akin. Thyroid functions of neonates with
Down syndrome, Italian Journal of Pediatrics 2012, 38:44

34. 
all patients with DS should be screened for
thyroid dysgenesis, and if present, lifelong
treatment with L-T4 should immediately be
started.
Ayşe Nurcan Cebeci, Ayla Güven, Metin Yıldız. Profile of
Hypothyroidism in Down’s Syndrome. J Clin Res Pediatr Endocrinol
2013;5(2):116-120

35. SH
Safe
medication
inteligence
treatment
symptomatic
hypotonia
Antibodies +
height
>5 mU/L
No treatment
Rare to
shift to OH
cost
No long
term study

37. 

Results Eighty-nine articles were retrieved
and reviewed for inclusion.
The guidelines on the medical management
of children with Down syndrome of five
expert groups have also been retrieved and
reviewed for this discussion.

38. 



(1) whether subclinical hypothyroidism
requires treatment;
(2) at what TSH level treatment should be
commenced;
(3) the optimal frequency of monitoring TFTs
(4) whether treating subclinical
hypothyroidism has any benefits for growth,
puberty and intellectual development.

39. 

Some recommend treatment with thyroxine
even in marginal cases of subclinical
hypothyroidism, to prevent progression to
more severe hypothyroidism.
Most authors who suggest treating
subclinical hypothyroidism suggest doing so
at TSH levels greater than 10 mU/L.

40. 
Arguments in favour of treatment include the
lack of adverse side effects associated with
thyroxine treatment and the possible
beneficial effects on the growth and
development of the affected child

41. 
Other found that TSH elevation was more
frequently associated with growth retardation
in those<4 years of age in comparison to
children with normal TSH levels.

42. 
Suggests beginning a trial treatment of
thyroxine in symptomatic cases of subclinical
hypothyroidism or those with positive thyroid
peroxidase antibodies

43. 

The 2001 Irish and 2001 UK guidelines both
recommend performing thyroid antibody
testing at each thyroid screen
The U.S. ,australian and Canadian guidelines
do not refer to thyroid antibody testing.

45. 

In conclusion, more evidence is required
regarding the optimal course of treatment for
subclinical hypothyroidism.
Such evidence may be best obtained by
conducting a prospective randomized control
trial.

46. APPENDEGES

47. 






Clinical diagnosis unreliable
Biochemical screening protocols essential
– venous protocol at age 1 and 2 yearly for
life OR
– annual fingerprick screen if available
Young children may have transitory high
TSH without hypothyroidism
Thyroxine treatment only indicated if
hypothyroidism is biochemically confirmed
Treatment as for general population

48. 

cost of a free T4 is $144, and the TSH test
costs $170;
thyroid hormone costs only $100–$200 per
year

49. 
The normal TSH range is defined as range in
which 95% of values in healthy people fall;
thus about 2.5% of normal individuals will
have and maintain a TSH at or slightly above
the upper end of the normal range.

50. 

Random TSH Variation.
TSH levels in healthy individuals tend to
fluctuate during the day as well as over
time. One study compared early morning
fasting and late morning TSH levels in
100 patients. In 97, TSH declined during
the morning, by a mean of 26%

51. 
Non-Thyroidal Illness. A child with an active
or recent acute illness may have a transient
drop in thyroid hormone production. During
the recovery phase, a transient increase in
TSH is the normal mechanism for restoring
normal free T4 levels, and TSH will