Paediatrics chapters
Congenital hypothyroidism and newborn screening
Thyroid hormone deficiency present from birth: why it is usually missed clinically, how newborn screening finds it, and why starting levothyroxine in the first weeks protects the brain.
- Congenital hypothyroidism affects about 1 in 2,000 to 4,000 babies; most cases are due to thyroid dysgenesis (absent, small or ectopic gland), not a hereditary defect.
- Babies look normal at birth; early clues are prolonged jaundice, poor feeding, constipation, large tongue, umbilical hernia, large posterior fontanelle and hypotonia, so diagnosis depends on newborn screening (raised TSH) confirmed by low FT4 and high TSH.
- Levothyroxine 10 to 15 micrograms/kg/day, started within the first 2 weeks, gives normal intelligence; delay beyond 6 months causes permanent intellectual disability.
On this page
Overview
Congenital hypothyroidism is a marked reduction or total absence of thyroid function present at birth. It is one of the commonest preventable causes of intellectual disability. Thyroid hormone is essential for brain maturation during the first two to three years after birth, but signs in the newborn are subtle and appear only after weeks. By the time the classic picture ("cretinism") is obvious, brain damage has already begun. That is why newborn screening and early levothyroxine are the key exam themes.
Thyroid hormone and the fetus
- The thyroid descends from the floor of the primitive mouth to the neck by the end of the first trimester; the hypothalamic-pituitary-thyroid axis works from the second trimester.
- T4, T3 and TSH cross the placenta only in small amounts, so fetal levels mostly reflect the fetus's own gland.
- Maternal thyroid antibodies, iodides (including radioactive iodine) and antithyroid drugs (carbimazole/methimazole, propylthiouracil) do cross and can affect the fetal thyroid.
- The fetus does not need thyroid hormone for growth, so affected babies have normal birth length and weight.
Thyroid hormone is needed for postnatal growth and brain maturation, not for fetal growth. A hypothyroid newborn therefore looks normal at birth.
Epidemiology
- About 1 in 2,000 to 4,000 live births (Nelson); Akbar quotes about 1 in 4,000 worldwide.
- Boys and girls equally affected.
- Most cases are sporadic, not inherited.
- Goitrous congenital hypothyroidism (inborn error of hormone synthesis or maternal antithyroid drugs) is much rarer, about 1 in 30,000.
- Isolated secondary or tertiary (pituitary or hypothalamic) hypothyroidism is rare, about 1 in 100,000.
Aetiology
| Group | Causes | Goitre? |
|---|---|---|
| Thyroid dysgenesis (about 90%) | Agenesis (athyreosis), hypoplasia, ectopic gland | No |
| Dyshormonogenesis | Inborn defects of iodide transport, organification, thyroglobulin synthesis or deiodination | Yes |
| Transplacental | Maternal antithyroid drugs, iodides, TSH-receptor blocking antibodies (usually transient) | May be |
| Iodine deficiency | Endemic goitre and endemic cretinism | Yes |
| Central | TRH or TSH deficiency (hypothalamic or pituitary) | No |
| Other | End-organ resistance to thyroid hormone; idiopathic | Variable |
The commonest cause is thyroid dysgenesis, not dyshormonogenesis and not iodine deficiency (iodine deficiency is the commonest cause where it is endemic).
Congenital TBG deficiency gives a low total T4 but normal FT4 and normal TSH. The child is euthyroid and needs no treatment.
Endemic cretinism (public health)
Severe iodine deficiency in pregnancy causes endemic cretinism, part of the spectrum of iodine deficiency disorders. Park describes two forms:
- Neurological cretinism: intellectual disability, deaf-mutism, squint and spastic diplegia.
- Myxoedematous cretinism: dwarfism, severe intellectual disability and hypothyroid features.
Both are prevented by correcting iodine deficiency, mainly with iodised salt.
Clinical features
The severity of signs matches the degree of hypothyroidism. Most babies look normal at first.
At birth and in the first weeks
- Post-term delivery (Akbar: gestation over 42 weeks in about half) and birth weight over 4 kg (about a quarter).
- Prolonged neonatal jaundice (common; Akbar quotes about 75%).
- Poor feeding, sleepiness, lethargy, little crying.
- Hypothermia, cold mottled skin, acrocyanosis.
- Large posterior fontanelle (and large anterior fontanelle).
- Respiratory distress, noisy breathing.
- Hypotonia, bradycardia.
After 1 to 2 months (the classic picture)
| System | Features |
|---|---|
| Face | Coarse facies, large protruding tongue (macroglossia), thick lips, depressed nasal bridge, puffy eyelids |
| Skin and hair | Dry, mottled, cold skin; scanty, dry, brittle hair; thin lateral eyebrows; non-pitting oedema (myxoedema); carotenaemia |
| Abdomen | Constipation, distended abdomen, umbilical hernia |
| Voice | Hoarse cry |
| Neuromuscular | Hypotonia, lethargy, slow relaxation of tendon reflexes (best seen at the ankle) |
| Blood | Anaemia |
| Later | Short stature with infantile body proportions (high upper-to-lower segment ratio), delayed teeth, delayed milestones, intellectual disability |
"Sleepy, Yellow, Constipated, Big-tongued, Hernia": a quiet, jaundiced, constipated baby with a large tongue and umbilical hernia is hypothyroid until proved otherwise.
Untreated severe disease leads to short stature, epiphyseal dysgenesis, delayed development and intellectual disability.
Newborn screening
- Clinical diagnosis alone is too late; screening allows treatment before 1 month of age.
- Most programmes measure TSH on a heel-prick (or cord blood) spot; a raised TSH is the usual trigger.
- Akbar advises screening within the first 10 days, and especially in any baby whose sibling was affected.
- Any positive screen needs an immediate confirmatory serum sample: low FT4 with high TSH confirms primary hypothyroidism.
- Preterm and growth-restricted babies may have immature thyroid tests that mimic hypothyroidism; repeat testing is needed.
National screening coverage in Pakistan varies by province and hospital; follow the current local programme and guideline.
TSH-based screening misses central (pituitary or hypothalamic) hypothyroidism, because TSH is low or normal. When central disease is found, check other pituitary hormones and do an MRI.
Investigations
| Test | Finding |
|---|---|
| Serum FT4 | Low (test of choice, unaffected by binding proteins) |
| Serum TSH | High in primary hypothyroidism; low or normal in central disease |
| Thyroid scan (technetium-99m or iodine-123) | No uptake = agenesis; uptake in an abnormal site (along the path of descent) = ectopic gland; increased uptake in a normal-sited gland = enzyme defect |
| Thyroid ultrasound | Presence, size and position of the gland |
| Knee X-ray | Absent distal femoral epiphysis in a term baby; later delayed bone age and epiphyseal dysgenesis (stippled, fragmented ossification centres) |
| Skull X-ray | Large fontanelles, wide sutures, wormian bones |
| ECG | Low-voltage complexes, bradycardia |
| Others | Anaemia; raised cholesterol; perchlorate discharge test for organification defects |
| Total T4 | FT4 | TSH | TBG | |
|---|---|---|---|---|
| Primary hypothyroidism | Low | Low | High | Normal |
| Secondary (pituitary) | Low | Low | Low/normal | Normal |
| Tertiary (hypothalamic) | Low | Low | Low/normal | Normal |
| TBG deficiency | Low | Normal | Normal | Low |
Low FT4 + high TSH confirms primary congenital hypothyroidism. Do not delay treatment waiting for the scan.
Treatment
- Lifelong levothyroxine (thyroxine), once daily by mouth.
- Starting dose in the newborn: 10 to 15 micrograms/kg/day (both books). The dose per kg falls with age; Nelson gives about 3 micrograms/kg/day later in childhood.
- Aim: raise FT4 rapidly into the upper half of the normal range. Full TSH suppression is not needed and can lead to overdosing.
- Start as soon as the diagnosis is confirmed; screening programmes aim to treat within 1 to 2 weeks of birth.
Newborn weighing 3.5 kg; dose 10 to 15 micrograms/kg/day
3.5 × 10 = 35 micrograms; 3.5 × 15 = 52.5 micrograms
Starting range: about 35 to 52 micrograms once daily
Signs of adequate dose and overdose
| Adequate dose | Overdose |
|---|---|
| More alert and active, better appetite | Diarrhoea, restlessness, excitability |
| Warm, smooth skin; constipation settles | Poor sleep, tachycardia, fever, tremor |
| Normal linear growth | Advanced bone age (long term) |
Follow-up
- Check growth (weight, length, head circumference), development and thyroid function regularly: about every 2 to 3 months in the first 2 years, less often afterwards (Akbar).
- Monitor bone age and developmental assessment at visits.
- Adjust the dose as the child grows to keep FT4 in the high-normal range.
"Test by day 10, treat by day 14."
Prognosis: early versus delayed treatment
| Timing of treatment | Outcome |
|---|---|
| Within the first month (ideally first 2 weeks) | Normal growth and intelligence expected |
| After about 6 months, when signs are obvious | High risk of permanent intellectual disability and neurological problems |
| Late at any age | Growth still improves, but brain damage does not reverse |
Growth catches up even in late-treated cases, but intelligence does not. This is the whole reason for newborn screening.
Expect: thyroid dysgenesis as the commonest cause (about 90%); normal size at birth because the fetus does not need thyroid hormone; early clues such as prolonged jaundice, constipation, lethargy, large tongue, umbilical hernia, large posterior fontanelle and hypotonia; the 18-month-old with coarse facies, constipation, umbilical hernia and delay; heel-prick TSH screening confirmed by low FT4 and high TSH; absent knee epiphysis and delayed bone age; technetium scan to separate agenesis from ectopic gland; levothyroxine 10 to 15 micrograms/kg/day started within 2 weeks; normal outcome with early treatment and permanent disability if delayed past 6 months; TBG deficiency needing no treatment; endemic cretinism from iodine deficiency.
Quick revision
- Incidence about 1 in 2,000 to 4,000; boys = girls; mostly sporadic.
- Dysgenesis (agenesis, hypoplasia, ectopic) about 90%; dyshormonogenesis gives a goitre.
- Normal at birth; prolonged jaundice, poor feeding, constipation, hypothermia, large posterior fontanelle.
- Later: coarse face, big tongue, umbilical hernia, hoarse cry, dry skin, delay.
- Screen with heel-prick TSH; confirm low FT4 and high TSH.
- Scan: no uptake = agenesis; abnormal site = ectopic; high uptake in normal gland = enzyme defect.
- Knee X-ray: absent distal femoral epiphysis; later delayed bone age, epiphyseal dysgenesis.
- Levothyroxine 10 to 15 micrograms/kg/day; FT4 to upper half of normal.
- Treat by 2 weeks: normal IQ; after 6 months: permanent damage.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics; Park's Textbook of Preventive and Social Medicine).
FAQ
Why do babies with congenital hypothyroidism look normal at birth?
The fetus does not depend on thyroid hormone for growth, and small amounts of maternal hormone cross the placenta, so length, weight and early behaviour can be normal.
What is the commonest cause?
Thyroid dysgenesis (an absent, underdeveloped or ectopic gland) causes about 90% of cases; inborn defects of hormone synthesis are much less common and usually produce a goitre.
Should treatment wait for a thyroid scan?
No. Once low FT4 and high TSH are confirmed, levothyroxine is started at once; the scan can be done later and only helps to define the cause.
What happens if treatment starts late?
Growth improves after treatment at any age, but intellectual disability caused by months of untreated hypothyroidism is permanent, especially when therapy begins after about 6 months.