Congenital

Ratna Dewi Artati

Hypothyroidism

Introduction
Hypothyroidism (H) def prod of the
thyroid hormone or defects thyroid
hormone receptor activity.
Thyroid hormones are crucial for :
Normal growth and development of the
brain and intellectual function, during
prenatal and early postnatal period.
Maturation of the foetal lungs and
bones.
Proper sexual maturation.

Delayed diagnosis growth failure and/or

irreversible mental retardation.
Diagnosis and initiation of appropriate
thyroid hormone treatment within
about the first 4 weeks of life
can prevent mental retardation
and growth failure.

Most infants with the disease have

no obvious clinical manifestations
at birth neonatal screening
of thyroid function should be
performed on all newborns.

The thyroid gland maintain the metabolic level of

almost all cells in the body.
producing 2 thyroid hormones in
its follicular cells : triiodothyronine
(T3) and tetraiodothyronine (T4) or
thyroxine.
Thyroid hormones synthesised in adult as long as the
dietary iodine supersedes 75 g daily
prevent goiter formation.

The hypothalamic-pituitary-thyroid axis

controls the thyroid gland function
and growth.
The production and release of thyroid
hormone
contolled by thyroid-releasing
hormone (TRH) from hypothalamus .

Epidemiology
H acquired or congenital, sporadic or
familial, goitrous or nongoitrous.
Congenital hypothyroid syndrome (CH) a
child is born with a def in thyroid
gland
activity or thyroid hormone levels.

The overall Incidence of CH 1 in

3000 to 1 in 4000 newborn infants,
the majority (90%) permanent CH.
Incidence of CH higher in Hispanic
and lower in black individuals.
Infants with Down Syndrome
increased risk.
Sex female : male = 2 : 1.

Etiology
Thyroid dysgenesis (sporadic form)
Most common cause; etiology unknown.
Includes agenesis (athyreosis), ectopicplacement of
the
gland and hypoplasia.
No goiter palpable on exam.
Theories suggest environmental teratogens.
Thyroid dyshormonogenesis(familial)
Mutations in genes that code for specific enzymes
and cofactors that are required for thyroid
hormonogenesis

Etiology
Transient Hypothyroidism
5 to 10% of infants detected with CH.
Maternal autoimmune thyroiditis with transplacental
passage of
maternal.
-TSH-receptor-blocking antibodies leading to inhibition of
TSH
action on the infants thyroid gland.
Maternal iodine deficiency, antithyroid drugs (PTU).
Hypothalamic-Pituitary (TSH deficiency)
Secondary (pituitary) or tertiary (hypothalamic) defects
are rare.
Generally associated with other pituitary hormone

Etiology
Thyroxine-binding globulin
deficiency
Low total T4
Normal free T4
X-linked dominant disorder
1 in 2400 male births
Euthyroid and does not require thyroid
hormone replacement

Permanent types of CH can be separated into

the following 3 categories:
1. Abnormalities of formation, migration,
and growth of the thyroid gland (thyroid
dysgenesis)
the thyroid gland is either absent, markedly
under-developed, or not in its proper
location (80-85%).
2. Abnormalities of enzymatic reaction
steps involved in thyroid hormone
production or release (thyroid
dyshormonogenesis)
deficiency of or an abnormality in one of

3. Abnormalities of the formation or

function of the hypothalamus and/or
pituitary (central hypothyroidism)
the thyroid gland forms and descends
properly, but the messenger hormone TSH is
either not produced or released properly from
the pituitary gland the thyroid gland does
not receive the TSH signal required for the
normal production and release of thyroid
hormone (<5%).

Clinical features of
CH:
At birth :

Postmaturity, birth weight >4

kg
Transient hypothermia
Large posterior fontanel (>5
mm)
Goitre
Early signs :
Placid, sleepy, hypoactivity
Poor feeding, failure to gain
weight

Later signs :

Failure to thrive
Dry skin, hair
Umbilical hernia
Macroglossia
Myxoedema
Hoarse cry
Slow responses
Delayed
development
Growth failure

Diagnosis
Primary Hypothyroidism
Elevated TSH (>20 mU/L,
generally > 50 for classic)
Low total or free T4
(varies for age)
Can also have normal T4
(subclinical)
Central Hypothyroidism
Low serum total and free
T4
Low or normal TSH
Thyroid binding globulin
deficiency
Low total T4, normal free
T4
Normal TSH

TYPE

FT4

TSH

Primary

Seconda
ry

Tertier

CLINICAL MANAGEMENT OF INFANTS

WITH
SUSPECTED CH :
(1) History
Maternal history of endemic iodine
deficiency,
thyroi disease, exposure to antithyroid
drugs and
goitrogens.
(2) Physical Examination
(3) Biochemical Thyroid Function Tests
Confirmatory measurement of TSH and T4
levels

(4) Bone Maturation

X-ray of both knees should be taken to assess bone
maturation bone age delayed
(5) Thyroid Scintigraphy
There has been controversy whether early thyroid
scanning should be performed before
commencement of thyroid replacement therapy.
(a) Absent gland athyreosis or severe hypoplasia
Indicates permanent hypothyroidism
(b) Decreased uptake at the normal site
thyroid hypoplasia

(c) Ectopic gland

Indicates permanent hypothyroidism
Usually sporadic
(d) Normal scan enzyme defect or transient
hypothyroidism

Treatment
Initial doses of L-thyroxine: 10-15 g/kg/day
General doses of L- thyroxine by age:

Age

mcg/kg/dose, daily

0 3 months

10 - 15

3 6 months

8 - 10

6 12 months

6-8

1 5 yrs

4-6

6 12 yrs

3-5

> 12 yrs

2-4

Goal of therapy :
- Normalize TSH to ensure optimal thyroid
hormone dosage and compliance
- Maintain T4 and FT4 in the upper half of
reference range during the first 3 years of life.
- In first year of life, serum T4 should be 10-16
mcg/dL and free T4 should be 1.4-2.3 ng/dL.

Follow-up:
Monitor T4 / TSH at regular
intervals
Monitor growth (weight / height)
Development assessment

AAP recommends measurement of serum T4 or free

T4 and TSH according to the following schedule: At 2 and 4 weeks after the initiation of L-T4
treatment .
Every 1 to 2 months during the first 6 months of
life.
Every 3 to 4 months between 6 months and 3
years of age.
Every 6 to 12 months until growth is completed.
At more frequent intervals when compliance is
questioned or abnormal results are obtained.

Assessment of permanence of CH :
If the thyroid scan shows ectopic/absent
gland, CH is permanent.
If initial TSH is <50 mU/L and there is no
increase in TSH after newborn period, then
trial off therapy at 3 y of age.
If TSH increases off therapy, consider
permanent CH.

Prognostic Factors
Early diagnosis and therapy
Severity at diagnosis
Initial replacement dose: high (10-15

mg/kg/d) better
Etiology: ectopic better
Compliance: education (parents, family
doctor)

Prognosis

Age of
treatment
(months)

Inverse relationship between age at clinical diagnosis of congenital hypothyroidism and IQ outcome

0-3
3-6
>6

Mean

89
71
54

IQ

Range

64 - 107
35 - 96
25 - 80

Prognosis
Detected and treated early in life
prognosis is quite good.
Long term sequelae mild mental
retardation, speech difficulty,
hearing deficit, short attention
span, or fine motor coordination
problems.

Neonatal Screening

Screening
CH - high prevalence
- mental retardation
- replacement therapy starts before 3
months of age favorable
prognosis.
Improvements in screening and therapy
improved developmental outcomes

Screening Method
1. Primary TSH with Backup T4 Measurements.

- primary TSH measurements.

- supplemented by T4 determinations for
infants with elevated TSH values.
- delayed TSH elevation in infants with
thyroidbinding globulin (TBG) deficiency, central
hypothyroidism, and hypothyroxinemia will
be
missed.

Screening Method
2. Primary T4 with Backup TSH Measurements.
- T4 measurement is followed by a measurement of
TSH with low T4 values.
- will detect primary hypothyroidism in infants with
low
or low-normal T4 with elevated TSH concentrations
infants, identify infants with TBG deficiency and
central hypothyroidism (low or low-normal T4
with normal TSH concentration).
- will miss an infant with an initially normal T4
concentration and delayed increase in TSH.

Screening Method
3. Combined Primary TSH Plus T4

Measurements.
- Ideal screening approach.

Screening Method

Management of CH
Initial workup :
Detailed history and physical examination
Referral to pediatric endocrinologist
Recheck serum TSH and FT4
Thyroid ultrasonography and/or thyroid
scan
Medication :
L-T4 : 10-15 g/kg once daily
Monitoring.

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