CHILDHOOD

HYPOTHYROIDISM
UNIT 1
DR AFR AABEDE
REGISTRAR
ANATOMY/EMBRYOLOGY
TG consist of bilateral lobes
that extend from the side of the
thyroid cartilage down on both
sides to the 6th tracheal ring
It also extend anterioly to the
isthmus overlying the 2nd and 3rd
rings of trachea.
The thyroids develops from a
bud which pushes out from the
floor of the pharynx and then
descends to it’s definitive
position in the neck
INTRODUCTION
• Hypothyroidism results from
deficient production of thyroid
hormone or a defect in thyroidal
hormonal receptor activity
• It can be congenital or acquired
• Congenital form can be further
subdivided into:
Primary (aplasia or hypoplasia
of TG)
Secondary (TSH deficiency)
Tertiary (TRH deficiency)
Embryology contd
The fetal thyroids bilobed shape
is recognizable by the seventh
wk GA.
By 12th wk GA the fetus
depends on it’s own pituitary –
thyroid axis for synthesis and
secretion of throid hormone
normal mature feedback
develops by 3rd month post
natal life.
physiology

The TG secrete T4 andT3.

T4 is the major hormone and is
controlled via negative
feedback loop.
THYROID HORMONE
PRODUCTION
• TG concentrates exogenous iodides
in the body and convert it to
hormonally active form.
• Iodide is actively transported into
TG by sodium-iodide
symporter(iodide trapping)
• Oxidation of iodide(thyroidal
peroxidase
• Iodination of tyrosal residue=within
tyroglobulin(mono and di
iodothyrosine)
• Mono+di iodotyrosine=T4
• Diodo+diodo tyrosine=T3
• T4+T3 stored as thyroglobulin
• Proteases and peptidases
release free Thyroid hormone
into circulation(regulated by
neg feedback
• Free hormone binds to TBG
• CONGENITAL HYPOTHYROIDISM
 Primary thyroid failure that is present at birth
 aetiopathogenesis:
1 -thyroid gland malformation
*agenesis: absent TG
*dysgenesis:ectopic(eg sublingual),
incorrectly formed(hemigland)
2-dyshormonogenesis(15 known defects)
3-transient hypothyroidism
*maternal ingestion of antithyroid drugs
*transplacental transfer of antithyroid
antibodies
*exposure to high levels of
iodine(povidone) in NNP
GENETICS
 Dysgeneis is usually sporadic

-1% familial

-mutation found in TSH-receptor gene & transcription

factors PAX-8 and TTF-2

 Dyshormonogenesis is inherited in AR pattern most

commonly:

*chromo 2p: mutations in thyroid peroxidase gene result

in partial or complete loss of iodide organification
function

*chromo 19p:mutations in the sodium-iodide symporter

gene result in an inability to maintain the normal thyroid-
to-plasma iodine concentration difference
EPIDEMIOLOGY
• Worldwide,the incidence of congenital
hypothyroididism is 1 in 3,000 to 1 in 4,000 births.
• In developing world especially Africa the incidence
is not known due to absence of neonatal
hypothyroidism screening.
• In Nigeria more cases of congenital hypothyroidism
are being seen out of 18 cases seen by Dr.Oduwole
in LUTH 14 were congenital and most presented
beyond NN period to mid infancy (personal
communication)
• 80% dysgnesis or agenesis;20%
dyshormonogenesis
• Racial differences: prevalence in black infants
about 1/3rd that in whites
• Higher prevalence of congenital hypothyroidism on
LBW babies<2000g and macrosomic babies>4500g
CLINICAL FEATURES
 In the developed world
*most children are diagnosed by
neonatal screening program.
*5-10% are false positive
*NN screening protocol differ from
country to country and in the USA
from state to state( T4 or TSH or
both)
 In the developing world (including
Nigeria)
*NN screening protocol non existent
*instead the clinical acumen and
high index of suspicion is used very
rarely (“the NN hypothyroid index”
)in few centres lucky enough to have
paediatric endocrinologists
*most presents beyond the 2nd -3rd
mo of life. When the clinical features
CLINICAL FEATURES
History
Usually become noticeable by 3-
6mo
M:F=1:2
Related to hypothyroidism:
*prolonged jaundice
*protuberant abdomen
*poor feeding *hoarse
voice 4 age
*constipation
*sluggishness/excessive sleep
*poor linear growth/delayed
CLINICAL FEATURES
Family history of thyroid disorders:
*auto immune thyroid disorders
*vague hx of “mild thyroidism”
frequently found in families withTBG
deficiency
Maternal medications
Birth history: ?asphyxia
Results of the newborn screen
where available/suggestive NN
hypothyroid screening
PMH-choking on feeding/prolonged
NNJ
CLINICAL FEATURES

Physical examinations
Signs relating to hypothyroidism:
*hypothermia
*large fontanelle’s (esp PF)
*wide cranial sutures
*coarse facial features
*macroglossia
*delayed DTR
*distended abdomen
*umbilical hernia
CLINICAL FEATURES

Physical examinations
Signs of possible goitre
Helpful tricks for examination:
*inspect base of tongue for an
ectopic gland
*while supporting the posterior
neck and occiput,allow the
infant’s head to hang back over
the parent’s arm or examination
table.
ACQUIRED
HYPOTHYROIDISM
Hypothyroidism that occurs after the
neonatal period
 Genetics
* genetic predisposition-CLT pts
*30-40% have familial hx
*50% of 1st degree relatives have
thyroid antibodies
*autoimmune thyroiditis(schmidt)-
stronger HLA linkage
*genetic syndromes have a higher
incidence of autoimmune thyroiditis
Aetiology: myriad
*auto-immune destruction by:
-chronic lymphocytic
thyroiditis(Hashimoto)
commonest in non endemic
areas
-autoimmune polyendocrine
syndrome(scmidt)
 *iodine deficiency disorders commonest in endemic
regions
*iatrogenic:
-antithyroid drugs(
-iodides
-irradiation
-subtotal thyroidectomy eg for thyroitoxicosis
*hypothalamic/pituitary lesions
*large heamangioma of the liver
*infectious:-postviral subacute thyroiditis
-associated with congenital infections
like rubella and toxoplasmosis
*environmental
-goitrogen ingestion like
iodide,expectorants and
thioureas
*metabolic- cytinosis and
histocytosis X
*congenital- late onset congenital
large ectopic gland
*genetic syndromes-
Downs,Turners
Epidemiology
*may develop at any age
*CLT prevalence correlates with
iodine intake directly
proportionately
*occurs`more frequently in
chilren with type 1 DM
Clinical Features of
acquired hypothroidism
Linear growth failure
Declining school performance
Timing of hypothyroid related
symptoms:
*early hypo+ asymptomatic
*symptoms indicates chronicity and
thus mean progression from
compensated to uncompensated
hypoth.
Any thyroid enlargement,its duration
and tenderness: may present with
Past medical hx factors assoc with
hypothyroid:
*genetic syndromes
*radiation exposure
*medication
*history of DM
Familial hx of hypo/hyperthyroidism
*any hx of such or other auto
immune endocrinopathies-increased
risk of autoimmune thyroiditis
Physical examination
 Short stature/fall-off on growth curve
 Increased upper segment/lower segment
ratio
 + goitre with its xtics(clues 2
cause+marker 4 ff-up)
*consistency
*symmetry
*nodularity
*signs of inflammation
 Myxedema(water retention)-not limited to
subcut tissue. May lead to CCF,pleural
effusion and coma
 Muscle hypertrophy+muscle weakness
 Pale,cool,dry caroteinemic skin
Tanner staging of sexual
development (both delayed and
precocious puberty can be
seen)
Galactorrhea is a possible
finding
INVESTIGATIONS CONG.
HYPO
NN screening program (filter card)
*methods vary from one developed
world to the other most screen for T4
then do the TSH for those with the
lowest 10th per centile of that day’
value.
Abnormal results leads to immediate
examination and confirmatory tests.
Serum T4 and TSH give the
confirmation.
* TSH= sensitive indicator of 10 hypo
NN hypothyroid index

A scoring system that can be used in

countries that cannot afford routine
screening program to aid early
diagnosis
It helps in selecting those babies
that need to have serum TSH and T4
+skeletal maturation
A score of more than 3 need to be
screened.
Reliability,reproducibity and how
NEONATAL HYPOTHYROID INDEX
CLINICAL SCORE
FEATURES
TYPICAL FACIES 3
DRY SKIN 1.5
OPEN POST. FONTANELLE 1.5
Feeding problem 1
Constipation 1
Poor activity 1
Poor muscle tone 1
Large tongue 1
Skin mottling 1
Umbilical hernia 1
Imaging studies
 Radiograph of the skeleton may show retarded
osseous development in 60% of affected newborn.
 Radionuclide studies with radioactive isotope 123I-
sodium iodide to evaluate iodine trapping or
concentrating mechanism of the thyroid or use of
technetium as pertachnate-may pin-ponit the
cause.
 Results:
*failed uptake=thyroid agenesis
*abnormal localisation=ectopic gland
*increased uptake=enzymatic defect in thyroid
hormone prod.
Imaging contd
CAUTION!!!
 Iodide scan must be done prior to
starting thyroxine and if it will delay
tmt pls postpone till brain growth is
complete(2-3yr
USS of thyroid can be done to
determine the location,size and
shape of the thyroid but is is not as
reliable as scintigraphy in suspected
dyshormonogenesis
ECG may show low voltage P and T
wave with diminished amplitude of
INVESTIGATIONS

False positives
*blood specimens obtained
before 48hrs of life may have
elevated TSH due to the normal
post-natal surge
*TBG def: total T4 is low but TSH
is normal.(x linked0
INVESTIGATIONS FOR ACQ
HYPOTHYROIDISM
 Same as for congenital forms essentially low T4 and
elevated TSH
 If TSH is normal or low, hypopituitarism or
hypothalamic lesion may be suspected
 Free T4 =MOST sensitive marker for the above
 In children older than 2yr of age serum cholesterol
is usually elevated.
 Skeletal maturation is markedly delayed
 Presence of circulating antibody(antithyroglobulin
and antimicrosomal) implies an autoimmune basis
 Head MRI for suspected 20 or 30 hypo,pit or
hypothalamic lesion.
False positive test for
acquired hypothyroidism
Thyroid binding globulin
deficiency =low total T4 but
normal free T4 and TSH
Peripheral resistance to thyroid
hormone =normal/high total T4
Euthyroid sick syndrome=low T4
and T3;norma/low TSH;
increased shunting to reverse
T3
TREATMENT
L-throxine 10-15ug/kg/day. Titrate to
keep T4 in the upper range of normal
(CH)
2-5ug/kg/day po once daily(AH)
titrate to maitain normal TFTs
Treatment is for life
No restrictioons on diet but soya
formulas and iron containing drugs
may interfere with absorption of L-
throxine
FOLLOW-UP
Whenever starting medication or adjusting
dose,check T4 and TSH 4-6 wks later to assess the
adequacy of the new dose
When to expect improvement:
*CH-parents may note increase in
activity,improvement in feeding and increase in
urination and bowel movement soon after.
*AH-catch up growth,other signs and symptoms
resolve at a variable rate
* Goitre in CLT may not regress with treatment.
Signs to watch out for
Poor growth and low T4 and
elevated TSH suggest poor
compliance and undertreatment
COMPLICATIONS
Congenital hypothyroidism
If untreated-severe
MR(cretinism)
Poor motor development
Poor growth
Acquired hypothyroidism If
untreated
Impaired linear growth
Myxedema coma
Encephalopathy
PROGNOSIS
 Congenital hypothyroidism
*Excellent if treatment is started within the
1st 4 ks of life (not usually the case here)
*level of T4 at birth is an important indicator
of long time sequalae.
 Acquired hypothyroidism
*If patients are compliants prognosis is
excellent.
*in those whom treatment has been
delayed catch up growth may not fully
normalise height to predicted values
• IS THERE A PLACE FOR
NEONATAL
HYPOTHYROID
SCREENING PROTOCOL
IN NIGERIA??
THANK
YOU
• FAQs
• Comparison of Downs syndrome and
Hypothyroidism
• Comparison of Beckwitt and
Hypothyroidism
• Causes of Hypotonia in infancy
• Causes of neonatal constipation
• Neonatal screening program in
developing world