hypothyrodsim in trisomy 21
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Thyroid dysfunction in trisomy 21
Yassin M Y Alsaleh
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: تعالى قال
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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.
definitoins
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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.
INTRODUCTION
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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.
INTRODUCTION
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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 .
epidemiology
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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%)
epidemiology
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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.
epidemiology
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The clinical symptoms and signs of both Downs syndrome and hypothyroidism are overlapping to some extent
manifestations
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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.
manifestationsmentality
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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
mentality
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thyroid dysfunction in down• congenital or
acquired
• hyper or hypothyroidism
• Compensated or uncompensated
• transient or persistent.
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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.
Subclinical hypothyroidism
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
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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.
Subclinical hypothyroidism
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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;132:726-730.
Subclinical hypothyroidism
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the most common cause of CH in DS is thyroid dysgenesis.
Congenital hypothyroidism
Devos H, Rodd C, Gagne N, et al. A search forthe possible molecular mechanisms of thyroiddysgenesis: sex ratios and associatedmalformations. J Clin Endocrinol Metab1999;84:2502–6.
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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
Acquired hypothyroidism
B Karlsson, J Gustafsson,Thyroid dysfunction in Down’s syndrome:relation to age and thyroid autoimmunityArch Dis Child 1998;79:242–245
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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.
Acquired hypothyroidism
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Positive anti-thyroid antibodies 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.
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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., “SerumTSH, T, and thyroid antibodies in theUnited States population(1988 to 1994): National Health and Nutrition ExaminationSurvey (NHANES III),” Journal of Clinical Endocrinology andMetabolism, vol. 87, no. 2, pp. 489–499, 2002.
Positive anti-thyroid antibodies
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prevention
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Mitchell C (1994) recommended a schedule of screening Down syndrome patients at 6 weeks 4, 10,16, 24 months and annually thereafter.
prevention
Mitchell C, Blachford J, Carlyle JM.ArchPediatr Adolesc Med 1994;148: 441- 442.
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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 dysfunctionin children Down Syndrome. Acta Pediatrica2001.
prevention
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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.
prevention
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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 re-release of American Academy of Pediatrics guidelines.
prevention
.Kecia N. Carroll, MD, MPH1Increase in Incidence of Medically-Treated 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
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Treatment
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Same as general population.
treatment CH
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the treatment approach to persistent compensated hypothyrodism is controversial.
McDermott MT, Ridgway EC. Subclinical hypothyroidism ismild thyroid failure and should be treated. J Clin EndocrinolMetab 2001;86:4585-90.
Chu JW, Crapo LM. The treatment of subclinicalhypothyroidism is seldom necessary. J Clin Endocrinol Metabolisim 2001
subclinical hypothyrodism
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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’ssyndrome; studies on myocardialstructure and function. Arch Dis Child 2003
subclinical hypothyrodism
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van Trotsenburg et al demonstrated that L-T4 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 two-year-old Down syndrome children= a randomized clinical trial. J Clin Endocrinol Metab 2005;90:3304-3311. Epub 2005 Mar 8
subclinical hypothyrodism
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that subclinical hypothyroidism and low-normal 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.
subclinical hypothyrodism
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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.
subclinical hypothyrodism
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
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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 withDown syndrome, Italian Journal of Pediatrics 2012, 38:44
subclinical hypothyrodism
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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
subclinical hypothyrodism
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SH
treatment
symptomatic
Antibodies +
>5 mU/L
No treatment
Rare to shift to OHcost
No long term study
Safe medicatio
n
inteligence
hypotonia
height
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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.
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(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.
??????
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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.
at what TSH level treatment should be commenced?
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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
whether subclinical hypothyroidism requires treatment?
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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.
whether subclinical hypothyroidism requires treatment?
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Suggests beginning a trial treatment of thyroxine in symptomatic cases of subclinical hypothyroidism or those with positive thyroid peroxidase antibodies
whether subclinical hypothyroidism requires treatment?
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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.
the optimal frequency of monitoring TFTs???
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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.
CONCLUSION
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APPENDEGES
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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
Down syndrome association recommendations
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cost of a free T4 is $144, and the TSH test costs $170;
thyroid hormone costs only $100–$200 per year
cost
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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.
TSH back to numbers
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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%
TSH back to numbers
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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
TSH back to numbers
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