congenital hypothyroidism

1. Dr.Shivani Bansal

2. Thyroid gland
 Thyroid is an
endocrine gland
situated at the root
of the neck on
either side of the
trachea.
 It has 2 lobes,which
are connected in the
middle by isthmus.

3. Hormones of thyroid gland-
 It secretes 3 hormones-
1. Tetraiodothyronine or T4(thyroxine)
2. Tri-iodothyronine or T3
3. Calcitonin
Function - Increase BMR
- stimulates growth in children
- increase oxygen consumption
- stimulate protein synthesis
- affect the carbohydrate ,lipid and vitamin
metabolism

4. Thyroid development and
physiology
 Fetal Development-the fetal thyroid bilobed
shape is recognised by 7 weeks of gestation.
 Characterstic thyroid follicle cells and colloid
formation is seen by 10 weeks
 Thyroglobulin synthesis occurs from 4 weeks
 Iodine trapping occurs by 8-10 weeks
 Thyroxine (t4) and triiodothyronine (t3) synthesis and
secretion occur from 12 weeks of gestation

5.  Hypothalamic neurons synthesise thyrotropin releasing
hormone (TRH) by 6 to 8 weeks.
 Pitutary portal vessel system begins development by 8 to 10
weeks.
 Thyroid stimulating hormone (TSH) secretion is evident by
12 weeks of gestation.
 Thyroid Physiology- the main function of thyroid
gland is to synthesise t4 and t3.
 The only known physiologic role of iodine is in the synthesis
of these hormones
 The recommended dietary allowance of iodine is 30 ug/kg/24
hour for infants,90-120 ug/24 hour for children,and 150 ug/24
hour for adolescent and adults

6. Synthesis of thyroid hormones

7.  The metabolic patency of t3 is 3 to 4 times
that of t4
 In adults thyroid produces approx 100 ug of
t4 and 20 ug of t3 daily
 Only 20% of circulating t3 is secreted by
thyroid
 The remainder is produced by de-iodination
of t4 in liver,kidney and other peripheral
tissues by type I 5 ‘ deiodinase.

8. Thyroid regulation

9. Hypothyroidism
Results from deficient production of
thyroid hormone or a defect in thyroid
hormone receptor activity
disese may manifest from birth or
acquired

10. Congenital Hypothyroidism-
 Congenital hypothyroidism (CH) is defined as
thyroid hormone deficiency present at birth
 most cases of congenital hypothyroidism are not
herediatory and result from thyroid dysgenesis
 Some cases may be famalial,usually caused by one
of the inborn errors of thyroid hormone synthesis
and may be associated with goiter.
 Incidence
 1: 4,000 newborns worldwide
 Hispanic, American Indian/Alaska Native
people (1:2,000 newborns)
 Black 1:3,2000 in black Americans

11. Etiology
 Common form of thyroid dysgenesis
 Aplasia
 Hypoplasia
 Ectopic gland (66%)
 Cause of thyroid dysgenesis is unknown (85%
sporadic, 15% hereditary)
 Mutations
 Inborn errors of T4 synthesis, secretion, or
utilization (2/3 heritable cases)
 Transient Hypothyroidism
 Maternal Autoimmune thyroiditis
 Maternal medication for Graves’ disease
 Endemic cretinism from iodine deficiency

12. Etiologic classification
Central or (Hypopitutary
hypothyroidism)
1. PIT 1 mutations-deficiency of
TSH,GH and prolactin
2. PROP 1 mutations-deficiency
of TSH, GH, prolactin ,LH ,FSH
+_ ACTH
3. TRH defeciency
4. TRH unresponsiveness
5. TSH defeciency
6. Multiple pitutary defeciency ex
cranio pharyngioma
7. TSH unresponsiveness
Primary hypothyroidism
1. Defect of fetal thyroid development-
aplasia,hypoplasia,ectopia
2. Defect in hormone synthesis-Iodine
transport defect, thyroid peroxidase
defect,Thyroglobulin synthesis
defect
3. Defect in thyroid hormone transport
4. Iodine defecincy-neurological type
,myxedematous type
5. Maternal antibodies-thyrotropine
receptor antibody
6. Maternal medications-radio iodine
,iodide,amiodarone

13. Clinical Manifestations
Infants protected for 1st few wks of life
 Fraction of maternal thyroid hormone crosses
placenta
 >40 wk GA
 Head size Slightly higher % due to brain myxedema
 Large fontanels & wide sutures
 Macroglossia
 Distended abdomen with umbilical hernia
 Rough dry skin
 Skin cold with mottling
 Sensorineural deafness (10%)
 Other congenital anomalies (10%)

14.  Sluggish feeding
 Constipation
 Lethargic
 Sleep more, needs to be
awakened to feed
 Hoarse cry
 Hypothermia
 Cardiomegaly
 Murmur
 Asymptomatic pericardial
effusion
 Macrocytic anemia
 Hypotonic with slow reflexes
 Prolonged physiological jaundice

15. If undiagnosed at a later age…
 Slow linear growth
 Loss of IQ
 Ataxia
 Gross/fine motor
incordination
 Hypotonia & spasticity
 Speech disorders
 Attention deficit
 Strabismus
 Sensorineural deafness
(10%)

16. Diagnosis:
 Primary hypothyroidism- low serum T4 & T3 and elevated
TSH values
 Free T4 and free T3 are more specific
 TSH is extremely sensitive index of primary hypothyroidism
 Radiographic studies- significant delay in skl. Maturation,
epiphyseal dysgenesis
 Imaging studies (U/S, radioisotope scan)- anatomical &
functional status
 Thyroid antibody study- autoimmune thyroiditis
 Sec./Tertiary hypothyroidism- TSH levels low or undectable
with subnormal levels of T3 & T4 as well as free T4 & T3 and
associated deficiency of other pitutiary hormones

17. Radiological finding
 Retardation of osseous development
 Absence of distal epiphysis
 Epiphyseal dysgenesis
 Deformity (beaking) of 12th thoracic or 1st or 2nd lumbar
vertebra
 Skull show large fontanels and wide sutures

18. Epiphyseal dysgenesis Shortening of long
bone
Large fontanel and wide
suture

19. Screening
 Started in Mid-1970’s
 Measure T4 & TSH > 48 hrs of life
 T4 – false-positive rate 0.30%
 TSH – false-positive 0.05%
 Preterm infants have higher false-positive
 If +  confirm  thyroid US or thyroid uptake scan
 If maternal autoimmune thyroid disease  measure TSH-
binding inhibitor Ig
 If iodine exposure/deficiency  measure urinary iodine

20. Screening
 Ideal is universal newborn screening at 3-4 days of age.
 Universal screening: Most cases are sporadic in Iodine sufficient
areas and intellectual impairment can be prevented if treatment
is initiated early.
 In the absence of universal screening, newborns with following
indications must be screened:
 1.Having clinical features of congenital hypothyroidism or family
history.
 2.History of thyroid disease or anti-thyroid medication intake in
mother.
 3.Presence of other conditions like Down’s syndrome, trisomy
18, neural tube defects, congenital heart disease, metabolic
disorders, familial autoimmune disorders are associated with
higher prevalence of congenital hypothyroidism.

21. Screening Approaches
 Newborn screening is done using cord blood or by
heel prick sample on dried blood spot filter paper at
2nd and 5th days of life.
 Three approaches are being used for screening:
 1. Primary TSH, back upT4
 2. Primary T4, back up TSH
 3. Concomitant T4and TSH

22. Screening Approaches
 1. Primary TSH, back upT4:
 TSH is measured first.
 T4 is measured only if TSH is > 20 mu/L.
 2. Primary T4, back up TSH:
 •T4is checked first
 •If it is low (< 6.5 μg/dL), then TSH is also checked.
 •This is likely to miss milder/ subclinical cases of CH
in which T4is initially normal with elevated TSH.
 3. Concomitant T4and TSH:
 •It is the most sensitive approach but incurs higher cost.
 Abnormal values on screening should always be
confirmed by a venous sample, using age appropriate
cut-offs.

23. Approach to a newborn with positive screening
test for Congenital Hypothyroidism
Positive screening test on filter paper sample
Serum T4/Free T4, TSH
Abnormal
Thyroid scan
Ectopic
Ectopic thyroid gland
Normal
Normal Absent uptake
START
TREATMENT-
DON’T WAIT
FOR SCAN

25. Age based reference values of
thyroid hormones

26. Treatment
 Infants with low T4 and elevated TSH should be
started on L-Thyroxine as soon as the diagnosis is
made.
 Initial dose of L-Thyroxine is 10-15 μg/Kg/day.
 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
15μg/Kg/day.

27.  Preferred preparation is Sodium
Levothyroxine. It has uniform potency, reliable
absorption and good bioavailability.
 Daily dose should be crushed and placed
directly on the tongue in the morning.
 Iron and Calcium preparations interfere with
its absorption.
 If a dose is missed, then double dose should be
given on the next day.

28. Monitoring:
 T4 andTSH should be monitored according to
following schedule.
 0 to 6 months Every month
 6 months to 2 years Every 2- 3 months
 Beyond 2 years Every 6 months
 6 to 8 weeks after any dose change.
 It takes less than a week for T4to raise and 4-5
weeks for TSH to normalize.
 Overtreatment-craniosynotosis & temprament
problem

29. Prognosis:
 Final outcome in CH is closely related to the :
- nature & severity of underlying thyroid abnormality.
- age at diagnosis & onset of treatment
- adequacy & regularity of treament
 Worldwide neonatal screening programs for CH have a
significant impact on reducing intellectual deficits in
hypothyroid infants diagnosed & treated early
 Early diagnosis & adequate treatment from 1st week of
life leads to normal linear growth & intelligence

30.  In severe affected infant with lowest T4 level have
reduce IQ level & neuropsychological sequelae.
 Without treatment child have mental deficient &
growth retarted.
 Delay in diagnosis & failure to correct initial
hypothyroxinemia rapidly, inadequate treatment &
poor compliance in first 2-3 yrs of life result in
variable degree of brain damage.
 When onset of hypothyroidism occur after 2yr of
age, outlook for normal development is much
better even if diagnosis & treatment have been
delayed.

31. Thank you……..