CONGENITAL HYPOTHYROIDISM

THYROID METABOLISM IN
PREGNANCY:

Various changes occur in maternal thyroid

physiology during pregnancy
Increased uptake and clearance of iodine
Thyroid gland volume
Increased thyroxine-binding globulin (TBG) levels.
Increased total T4 and T3 levels.
Human chorionic gonadotropin (hCG) has
thyrotropin(TSH)-like activity
Transplacental passage.: Iodide and TRH
readily cross the placenta, but The placenta is
impermeable to TSH.
 Maternal thyroid hormones are
important for fetal development in
the first trimester before
establishment of the fetal HPT axis
First-trimester TSH response is more
blunted (when free T4 levels are the
highest) compared with the second
trimester,
 Fetal Thyroid Function

The fetal thyroid

Actively concentrates iodide after 10 weeks,
Releases T4 after 12 weeks,
Responsive to pituitary TSH at 20 weeks of gestation.
Circulating TSH and T4 levels are minimal until
approximately 18 to 20 weeks. After 20 weeks,
there is a progressive increase in TSH and free T 4
level
There is an increase in the T4:TSH ratio,
suggesting maturation of the negative feedback
control of the HPT axis
T3 levels also progressively increase, although
later, after approximately 30 weeks of gestation.
 Neonatal physiology:

Thyroid hormone levels are related to gestational

age and birth weight
Preterm infants demonstrate similar changes in
thyroid hormone levels as full-term newborns.
But ,quantitatively the response is blunted because
of axis immaturity
At birth there is a sharp increase in TSH as a result
of neonatal cooling, This surge peaks at 30 minutes
and declines over the next few days
The increased TSH results in a concomitant sharp
rise in T4 and T3 levels, peaking at 36 to 48 hours of
life, and then steadily declining to adult values over
4 to 5 weeks
 Normal ranges in the
newborn period
and later life
At birth the newborn experiences a
sharp thyroid surge. TSH rises rapidly,
up to 60uIU/ml, followed by a rise in T4;
then gradually both fall to baseline over 2-
3 days.
So the cutoffs for the first 72 hours of life
for TSH and T4 are much higher, e.g. TSH
even up to 50 may be normal at 24 hr of
life.
By day five of life, the TSH settles to <10
uIU/ml. By 10-14 weeks of life the TSH
settles to the adult range, i.e. < 5 uIU/ml.
In the preterm baby:
The pattern of the thyroid surge follows the
same time pattern, but the peaks achieved
may be somewhat lower.
When in doubt, TH should be repeated in a
weeks time, so replacement is not unduly
delayed.
At the same time, unnecessary thyroxin does
not improve outcomes, and should be avoided
if the sick euthyroid syndrome is likely to be
present.
 INCIDENCE
The worldwide incidence is 1:3000-4000 live births
incidence in India is 1:2500-2800 live births.
Thyroid dysgenesis is the commonest cause
accounting for 75-80% of all cases.
The male to female ratio is 1 : 2.
Delayed treated of CH results in mental development
delays.
One study demonstrated that the average IQ was 89,
70, and 54 if therapy started before 3 months,
between 3 and 6 months, and after 6 months of age,
respectively.
 CLASSIFICATION

PERMANENT
TRANSIENT
HYPOTHYROXINEMIA WITH DELAYED
TSH RISE
 CAUSES OF PERMANENT CH

1) THYROID DYSGENESIS
2) DEFECTS IN THYROID HORMONE
SYNTHESIS
AND SECRETION
3) TSH RESISTANCE
4) CENTRAL HYPOTHYROIDISM
 CAUSES OF TRANSIENT CH

ANTITHYROID DRUGS
IODINE EXCESS
IODINE DEFICIENCY
TRANSIENT HYPOTHROXINEMIA OF
PREMATURITY
TSH RECEPTOR BLOCKING IgG
ANTIBODIES
LARGE LIVER HAEMANGIOMAS
1) ANTITHYROID DRUGS:
Intrauterine exposure to antithyroid
drugs like propylthyouracil carbimazole
methimazole,amiodorone.
Typically resolves with in 1week,and
does not require any treatment
2) IODINE DEFICIENCY:
Most common cause of transcient
hypothyroidism,particularly in preterms
 3) IODINE EXCESS:
Exposed to iodine excess in perinatal and
postnatal period
Preterm infants susceptible to thyroid
suppressing effect of excess iodine
Through mother milk,and in mothers who ingest
large amount of seafoods
Goitre may be present
RAI and 99mTC uptake is bloked by iodine excess
USG normally positioned thyroid gland
TRANSIENT HYPOTHYROXINEMIA OF
PREMATURITY

Hypothalamic pitutary immaturity (<

27 wks gestation),acute illness and
medication eg., dopamine and
steroids
TSH is inappropriately normal
Total T4 is more effected than free T3
Treatment contraversial but benificial
to infants <27 wks
TSH receptor IgG ANTIBODIES
Known maternal autoimmune thyroid disease
Half life 2 weeks
Both stimulating and blocking antibodies
Hypothyroidism persists 2 to 3 months
Goitre is not present
T4 is low TSH is elevated and TBG is normal
High concentration of TSH receptor-blocking
antibodies present in maternal and neonatal
serum
Thyroid scan absent uptake
USG thyroid gland seen
LARGE LIVER HAEMANGIOMAS

Refractory hypothyroidism due to

expression of D3 Deiodinase activity
by haemangiomas
Present after newborn period as
haemangiomas enlarges
Treatment large doses of L-thyroxine
Resolves as haemangiomas
regresses
 Hypothyroxinemia with delayed TSH
elevation ( atypical CH )

In infants < 1500 gms

Critically ill newborns including
congenital heart disease
Delayed TSH elevation may be
missed on initial screen, particularly
in primary TSH screeing programs
Repeat testing at 2 to 6 weeks age
 CLINICAL FEATURES
0 TO 7 DAYS 1 TO 4 WEEKS 1 TO 3 MONTHS

PROLONGED JAUNDICE FAILURE TO GAIN FAILURE TO THRIVE

> WEIGHT
3DAYS
CONSTIPATION UMBILICAL HERNIA
POOR FEEDING
HYPOACTIVITY MACROGLOSSIA
BIRTH WEIGHT > 4 KGS

TRANSIENT
chocking MYXEDEMA

HYPOTHERMIA and
apneic
episodes
LARGE POSTERIOR HOARSE CRY
CLINICAL FEATURES { MISCELLANEOUS}

Asymptomatic at birth
Length and weight normal
Puffy face
Coarse facial features
Dull look
 Short stature
Sleeps a lot
Rarely cries or hoarse cry
Dry brittle hair; low hairline
Poor muscle tone
Cool and pale mottling skin
Goiter (enlarged thyroid)
Birth defects (eg, heart valve, hearing)
Poor weight gain due to poor appetite
 Slow pulse
Swollen hands, feet and genitals
Cardiomegaly ,pericardial effusion
Macrocytic anemia (not responds to
hematanics)
 diagnosis
Newborn thyroid screening:
Screening should be done in EACH AND
EVERY newborn as it is very common (1:
1100 1: 3000 ) & almost impossible to
pick up clinically (95% affected
newborns look normal),
Very devastating to miss (results in
permanent mental retardation).
Testing by cord blood sampled from the
placental end for TSH or heel prick
sampling on a filter paper can be done.
 Screening approach
Three approaches are being used for
screening:
1. Primary TSH, back up T4
2. Primary T4, back up TSH
3. Concomitant T4 and TSH
1. Primary TSH, back up T4: TSH is measured first,
and T4 is measured only if TSH is >20mu/L. This
approach is most widely used and cost-effective,
but likely to miss central hypothyroidism, thyroid
binding globulin (TBG) deficiency and
hypothyroxinemia with delayed elevation of TSH.
2. Primary T4, back up TSH: T4 is checked first and if
low, TSH is also checked. This is likely to miss
milder/subclinical cases of CH in which T4 is initially
normal with elevated TSH.
3. Concomitant T4 and TSH: Most sensitive approach
but incurs a higher cost.
 Screening programs use either percentile
based cut-offs T4 below 10thcentile or
TSH above 90thcentile) or absolute cut-
offs such as T4 <6.5 ug/dL and TSH
>20mu/L. Among infants with proven CH,
TSH is >50 mu/L in 90% and T4 is <6.5
ug/dL in greater than 75% of cases.
Abnormal values on screening should
always be confirmed by a venous
sample (using age appropriate cut-offs
In the absence of universal screening, newborns
with the following indications should be
screened:
1. Family history of CH
2. History of thyroid disease or antithyroid medicine
intake in mother
3. Presence of other conditions like Down syndrome,
trisomy 18, neural tube defects, congenital heart
disease, metabolic disorders, familial
autoimmune disorders and Pierre-Robin syndrome,
which are associated with higher prevalence of CH
 QUEBEC SCORING
CLINICAL STIGMATA SCORING
FEEDING PROBLEMS 1
CONSTIPATION 1
LETHARGY 1
HYPOTONIA 1
COARSE FACIES 3
MACROGLOSSIA 1
OPEN POSTERIOR FONTANEL 1.5
DRY SKIN 1.5
MOTTLING OF SKIN 1
UMBILICAL HERNIA 1
TOTAL 13

If the score is > 4 / 13, hypothyroidism is suspected and the child is

investigated
accordingly
When should confirmatory repeat TH
testing be done?

Each newborns TSH report is ready at

discharge from the hospital, advise a
repeat test in a venous sample for TSH
and T4 if the report is abnormal, and start
replacement once the CH is confirmed.
If the baby does have CH, treatment
should be started as soon as possible,
since IQ starts dropping if replacement
does not begin by the age of 2 weeks.
 Diagnostic studies for evaluation of CH

1. Imaging Studies: will determine location

and size of thyroid gland
a. Scintigraphy (99mTc or 123
b. Sonography
2. Function Studies
a. 123 I uptake
b. Serum thyroglobulin
3. Suspected inborn error of T4 synthesis
a. 123 I uptake and perchlorate discharge
 4. Suspected autoimmune thyroid
disease
a. Maternal and neonatal serum
TBII measurement (not routinely
available)
5. Suspected iodine exposure or
deficiency
a. Urinary iodine measurement
6. Ancillary test to determine
severity of fetal hypothyroidism
 Treatment of CH

Term as well as preterm infants with low T4 and

elevated TSH should be started on L-thyroxine
The initial dose of L-thyroxine should be 10-15
g/kg/day with the aim to normalize the T4 level
at the earliest.
Those infants with severe hypothyroidism
(very low T4, very high TSH and absence of
distal femoral and proximal tibial epiphyses on
radiograph of knee) should be started with the
highest dose of 15g/ kg/ day.
 Adequacy of the dose requires careful
monitoring. Remember that TSH
CHANGES VERY SLOWLY, taking as much
as 4-5 WEEKS TO STABILIZE completely.
So initially, test the infants T4 every 2
weeks, to make sure the dose is not too
much or too little.
Check the TSH only after 4-6 weeks.
Thereafter, monitoring of T4, TSH and
growth should be done
Giving the thyroxin correctly:
The entire dose should be given once daily,
as the half life is 72 hours.
It is not necessary to give thyroxin in the
fasting state; what is important is the timing
should be consistent.
Iron, soya or calcium, are not given within
4-8 hours of administering thyroxin.
Drugs such as carbemazepine, phenytoin,
rifamipicin, estrogen, may increase the
metabolism and thus the dose of thyroxin.
Long periods of over-treatment with thyroxin
interfere with bone loss, and can increase the
risk of osteoporosis in later life.
 If multiple endocrine deficiencies exist
together, it is important to replace
cortisol before starting thyroxin, otherwise
an adrenal crisis can be precipitated.
Thyroid hormone increases the rate at
which adrenal glucocorticoids are
inactivated by the liver.
This leads to feedback increase in
adrenocorticotropic hormone production by
the anterior pituitaryand,
 Monitoring of therapy:
1) T4 should be kept in the upper half of normal
range (10 to 16 g/dL) or free T4 in the 1.4 to
2.3 ng/dL range with the TSH suppressed in the
normal range.
2) Check T4 and TSH levels according to the
following schedule:
0 to 6 months: every 6 weeks
6 months to 3 years: every 3 months
Beyond 3 years: every 6 monthly
6 to 8 weeks after any dosage change.
3) Monitor growth and development of the infant.
4) Avoid over treatment as it can lead to
premature fusion of cranial sutures, acceleration
of skeletal maturation and problems with
 Confirming permanancy
1) As much as 50% of CH may be transient, so at
the age of 3 years, thyroxin should be stopped for
5-6 weeks, and TH testing and imaging repeated.
2) Testing should not be done too early, e.g.
within 4 weeks of stopping.
3) Replacement should be restarted if the TSH
rises, and the need for lifelong replacement
emphasized to the parents.
4) Indications for TH testing include slow height
gain, delayed puberty, precocious thelarche or
menarche, chronic anemia, chronic constipation,
 poor scholastic performance, irregular periods or
menorrhagia, unexplained weight loss, weight
gain in a child who is short/ slowly growing,
goiter, lipid abnormalities, hyperprolactinemia,
etc.
In children with autoimmune diseases like type
1 diabetes, vitiligo, celiac disease, pernicious
anemia; polyendocrine failure syndromes (type 1
and 2); family history of thyroid disorders;
certain medications or conditions such as Down
syndrome, thyroid function should be tested
periodically.
Sources of confusion in interpreting

One may see a high TSH along with a high

T4. This can happens if the thyroxin was
missed in the preceding weeks, and just before
the test a larger dose than advised is given to
the child.
While the high dose raises the T4, there
was not enough time for the TSH to normalize.
In this situation, better compliance should
be emphasized, rather than increasing the
dose.
B) One may see a normal TSH, with low normal
T4. If the test was done mid afternoon or
evening, the diurnal variationin T4 levels
may bring it to a low level.
Dose increase is not needed.
C) Subclinical hypothyroidism borderline
high TSH (5-10 uIU/ml) with normal T4.
If the child is obese and tall for age and
MPH, this may be due to just obesity.
Treatment with thyroxin is not warranted for
simple obesity.
 Outcome

The best outcome occurs with therapy started by 2

weeks of age
Residual defects can include impaired visuospatial
processing and selective memory and sensorimotor
defects .
More than 80% of infants given replacement therapy
before 3 months of age have an IQ greater than 85 but
may show signs of minimal brain damage, including
impairment of arithmetic ability, speech, or fine
motor coordination in later life.
When treatment is started between 3-6 months, the
mean IQ is 71 and when delayed to beyond 6 months,
the mean IQ drops to 54