Congenital Hypothyroidism

Dr. Md. Masudur Rahman

Medical Officer
SCANU
Cox’s Bazar Sadar Hospital
Congenital Hypothyroidism:

- Congenital hypothyroidism
(CH) is defined as a significant
decrease in, or the absence of
thyroid function at or shortly after
birth.
CONGENITAL HYPOTHYROIDISM….

……..most common preventable

cause of mental retardation.

…..Unrecognized CH leads to
intellectual disability.
Incidence:
 1 in 2000 to 3000 live newborn infants.

 Sporadic cases account for 85% of patients,

whereas 15% are hereditary.

The incidence of CH is higher in Hispanic

individuals and lower in blacks.

2:1 female-to-male ratio.

CH is also more common in……
 Infants with trisomy 21

 Congenital heart disease ( pulmonary

stenosis ,ASD, VSD)

 Congenital malformations including

cleft palate and renal, skeletal, or
gastrointestinal anomalies.
 Development And Physiology:
Fetal thyroid bilobed shape is recognized by 7
weeks of gestation.

Thyroid follicle cells and colloid formation is

seen by 10 weeks.

T4 and T3 synthesis and secretion occur from 12

weeks
TRH synthesis by 6 to8 weeks
 Development And Physiology:
 TSH secretion by 12 weeks
TSH from fetal pituitary gland increases from
midgestation.
Fetal HPT axis develops independent of the
mother due to the high placental
concentration of D3(inactivates T4 from
mother)
negative feedback mechanism of HPT axis
starts to mature by 26 weeks
Neonatal physiology
30 minutes after delivery-dramatic surge in TSH,
with peak at 6 hours of life, followed by a rapid
decline over 24 hours

TSH surge -stimulates the neonatal thyroid

gland.

Serum T3 and T4 levels increase sharply and peak

within 24 hours of life, followed by a slow decline
Neonatal physiology cont…
 preterm infant TSH surge is less marked,
and the T4 and T3 responses are blunted.

<31 weeks’ gestation no surge seen and,

instead T4 fall for 7 to 10 days.
Classification:
 A. Primary hypothyroidism
1. Developmental defects Of Thyroid
Gland.
2. Inborn errors of thyroid hormone
synthesis.
3. Maternal exposure to radioiodine,
propylthiouracil (PTU) or methimazole (MMI)
during pregnancy.
4. Iodine deficiency (endemic cretinism)
B. Secondary hypothyroidism.
TSH deficiency.
 C. Tertiary hypothyroidism.
Thyrotropin-releasing hormone
(TRH) deficiency.
D. Hypopituitary hypothyroidism:
Associated with other hormonal
deficiencies.
 Classification
Permanent

Transient

Hypothyroxinaemia with delayed TSH rise

Causes of permanent CH
1. Thyroid dysgenesis

2. Defects in thyroid hormone synthesis and

secretion (Thyroid dyshormonogenesis)

3. TSH resistance

4. Central (hypothalamic–pituitary)
hypothyroidism
 1.Thyroid dysgenesis
85% of cases.
Aplasia, hypoplasia or dysplasia;
No goiter
Low total and free T4 levels, elevated TSH
Normal TBG.
Thyroglobulin (TG) :low in aplasia and hypoplasia
Confirmed absence by USG and/or thyroid
scintiscanning with radioactive iodine (RAI) or
pertechnetate (99mTc)
2.Defects in thyroid hormone synthesis and
secretion (Thyroid dyshormonogenesis)
 10% to 15%
 25% recurrence risk -siblings.
 synthetic defect is -abnormal thyroid peroxidase activity
 Pendred syndrome –goiter +sensorineural deafness
 Goiter present.
 Total and free T4 levels are low, TSH is elevated
 TBG is normal.
 serum TG: low in TG synthetic defects and high in other
thyroid hormone synthetic defects.
 Imaging reveals a normally placed thyroid gland
 3. TSH resistance

mutations in the TSH receptor gene.

thyroid gland is small.

T4 is normal or low and TSH is elevated

 4.Central (hypothalamic–pituitary)
hypothyroidism
 Other signs of pituitary dysfunction, -hypoglycemia,
microphallus, and midline facial abnormalities.
 Septo-optic dysplasia -important cause of central
hypothyroidism.
 Goiter is not present.
 Total and free T4 are low, TSH is low or inappropriately
normal,
 TBG is normal.
 Cortisol and growth hormone measured
 (MRI) scan done to visualize the hypothalamus and
pituitary gland
 Causes of transient CH
1. Antithyroid drugs
2. Worldwide, iodine deficiency
3. Iodine excess.
4. Transient hypothyroxinemia of prematurity
5. TSH receptor-blocking IgG antibodies
6. Large liver hemangiomas
 1.Antithyroid drugs

 Intrauterine exposure to PTU or MMI

 Typically resolves within 1 week and does not require

treatment
 2.Worldwide iodine deficiency
 Most common cause of transient hypothyroidism,
particularly in preterm
 3.Iodine excess.
 Exposed to excess iodine in the perinatal and/or
neonatal period.
 Preterm infants –susceptible to thyroid suppressing
effects of excess iodine
 Through breast milk and in mothers who ingest large
amounts of seaweed (e.g., in Japan).
 Goiter may be present.
 T4 is low and TSH is elevated.
 RAI or 99mTc uptake is blocked by excess iodine,
 Ultrasound -normally positioned thyroid gland
 4.Transient hypothyroxinemia of
prematurity
 m/c <31 weeks’ gestation
 Hypothalamic–pituitary immaturity (< 27 weeks’
gestation), acute illness, and medications (e.g.,
dopamine, steroids).
 TSH is inappropriately “normal.”
 Total T4 is more affected than free T4
 Neonatal death, intraventricular hemorrhage,
periventricular leukomalacia, cerebral palsy, intellectual
impairment, and school failure.
 Tx controversial but beneficial to infants <27 weeks’
gestation.
5.TSH receptor-blocking IgG antibodies
 1% to 2%
 known maternal autoimmune thyroid disease.
 half-life 2 weeks.
 Both stimulating and blocking antibodies present
 Hypothyroidism persists for 2 to 3 months
 Goiter is not present.
 T4 is low, TSH is elevated, and TBG is normal.
 High concentrations of TSH receptor-blocking
antibodies present in maternal and neonatal serum.
 thyroid scintiscanning, uptake absent,
 thyroid gland seen on ultrasound
6.Large liver hemangiomas
 Refractory hypothyroidism due to expression of D3
activity by the hemangioma

 Present after the newborn period as the hemangioma

enlarges.

 Tx- Large doses of L-thyroxine

 Resolves as the hemangioma regresses

Hypothyroxinemia with delayed TSH
elevation (atypical CH)
 Due to recovery from sick euthyroid syndrome

 Infants < 1,500 g

 Critically ill newborns including congenital heart
disease.

 Delayed TSH elevation may be missed on the initial

screen, particularly in primary TSH screening programs.

 Repeat testing at 2 to 6 weeks of age

 Over
Diagnosis & Screening method
But
95% of universal
newborn
newbor
screening
ns with allows for
CH are early
asympt diagnosis
omatic and
at birth treatment
Newborn screening for CH
Some programs measure T4 for the primary screen,
followed by TSH when T4 is low,

other programs measure TSH as the primary screen

(UAE)
advantages and disadvantages to each approach.

Few measure both T4 and TSH in the initial screen for

all newborns
 Timing:
 The ideal time for screening is 48 hours to
4 days of age.

 Infants discharged before 48 hours should be

screened before discharge; however, this
increases the number of false positive TSH
elevations

 A repeat test at 2 to 6 weeks identifies

approximately 10% of cases
Diagnostic studies
1. Serum for confirmatory measurements of T4 and
TSH concentrations:
If an abnormality of TBG is suspected, free T4
(FT4) and TBG concentrations should also be
evaluated.

2. Ultrasonography: is used to separate a structural

defect from a normal or enlarged gland.
Diagnostic studies
3. Thyroid scan (scintigraphy) with radioactive
iodine or technetium:
remains the most accurate diagnostic
modality to determine the cause of CH.
4. Knee radiographs:
may be used to assess the severity of
intrauterine hypothyroidism by the presence or
absence of femoral and tibial epiphyses..
Diagnostic studies:
5. Genetic testing and counseling:
are indicated with inborn errors of
thyroid hormone synthesis and when a
mutation in 1 of genes involved in thyroid
gland formation is suspected.
 Treatment and monitoring
 For infants with suspected transient or permanent CH
L-thyroxine 10 to 15 mcg/kg/day,
 normalize thyroid hormone:
- with total T4 in the 10 to 16 mcg/dL range,
- free T4 1.4 to 2.3 ng/dL, and
-TSH > 0.5 to 2 mU/L
 Normalise T4 within 1 week and TSH 2 weeks,.
 Lab after 1 week after starting therapy, 2 weeks after any
dose change, and every 1 to 2 months in first year of life.
 Preparation of L-Thyroxine
Crushed and fed directly to the infant or mixed in a
small amount of juice, water, or breast milk.

Soy-based formulas, ferrous sulfate, and fiber

interfere with absorption

2 hours early

No liquid preparations

Follow-up

Clinical evaluation, including assessme-

nt of growth and development, should
be performed every few months during
the first 3 years of life.
 Serum T4 and TSH measurements
should be performed as follows:
1. At 2 and 4 weeks after initiation of L-T4 therapy.
2. Every 1 to 2 months during the first 6 months of life.
3. Every 3 to 4 months between 6 months and 3 years.
4. Every 6 to 12 months until growth is completed.
5. More frequent intervals with dose change, abnormal
values, and compliance concerns.
6. Monitoring more intensely during puberty is
recommended to prevent unwanted cardiovascular
dysfunction.
 Suspected Transient CH:
Brief trial off medication can be attempted
at 3 years of age, after thyroid hormone-
dependent brain development is complete.

 Dose required to maintain normal thyroid

function does not change with age
Prognosis:

Neuro developmental outcome is excellent

Subtle viso-spatial processing, memory, and sensori-motor defects have been

reported in severe CH-significance controversial

diagnosed late may have substantial cognitive and behavioral defects

 Take Home Message
Compulsory
screening without
any miss or error

Repeat test if any

doubt

All with low T4

Early treatment- and high TSH are
Excellent CH until proved
recovery otherwise

Scanning, Consultation with

should not delay pediatric
Rx endocrinologist
Thank You…