Internal Medicine

Congenital hypothyroidism (CH)

Thyroid hormone deficiency at birth.

Thyroid hormone deficiency at birth.

  • M/C preventable cause of mental retardation


Primary (permanent) CH:

In iodine sufficient countries, 85% of congenital hypothyroidism is due to thyroid dysgenesis
  • Thyroid dysgenesis (M/C cause in India, 75%)
    • Thyroid ectopy (⅔ thyroid dysgenesis cases): Ectopic location of the thyroid gland
    • Athyreosis (complete absence of thyroid tissue) and thyroid hypoplasia (remaining ⅓ cases)
  • Dyshormonogeneses: Inborn errors of thyroid hormone biosynthesis

Secondary (central) CH:

  • Congenital hypopitiutarism (common)
  • Isolated TSH deficiency

Transient CH:

  • Preterm infants born in areas of endemic iodine deficiency

Syndromic association:

Gene mutations causing congenital hypothyroidism can be a rare cause of distinct clinical phenotypes
  • Pendred syndrome (pendrin mutation): Hypothyroidism- deafness – goiter)
  • Bamforth-Lazarus syndrome (TTF-2 mutation): Hypothyroidism – cleft palate – spiky hair)
  • Ectodermal dysplasia: Hypohidrotic – hypothyroidism – ciliary dyskinesia
  • Hypothyroidism – (dysmorphism – postaxial polydactyly – intellectual deficit)
  • Kocher-Deber-Semilange syndrome: Muscular pseudohypertrophy-hypothyroidism
  • Benign chorea-hypothyroidism
  • Choreoathetosis (NKX2.1 /TTF-1 mutation): Hypothyroidism – neonatal respiratory distress
  • Obesity – colitis – (hypothyroidism – cardiac hypertrophy – developmental delay)
Bamforth- Lazarus syndrome. An 8 month old infant with a homozygous mutation in the TTF-2 gene locus leading to congenital hypothyroidism. Phenotypic features include, low set ears, extensive cleft palate, hypertelorism, spiky hair and low posterior hairline. | A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate; Human Molecular Genetics, 2002, Vol. 11, No. 17. Courtesy Dr. Michel Polak and the Oxford University Press.

Clinincal features

The clinical features of congenital hypothyroidism are often subtle and many newborn infants remain undiagnosed at birth. This is due in part to passage of maternal thyroid hormone across the placenta.

  • Lethargy: Quiet baby and may sleep through the night
  • Feeding difficulty
  • Hoarse cry
  • Constipation, non-responsive to treatment
  • Prolonged jaundice (early sign, lasting for > 3 weeks): Delayed maturity of hepatic glucuronyl transferase
Infant with congenital hypothyroidism. A – 3 month old infant with untreated CH; picture demonstrates hypotonic posture, myxedematous facies, macroglossia, and umbilical hernia. B – Same infant, close up of face, showing myxedematous facies, macroglossia, and skin mottling. C – Same infant, close up showing abdominal distension and umbilical hernia. | Rastogi, M. V., & LaFranchi, S. H. (2010). Congenital hypothyroidism. Orphanet journal of rare diseases, 5, 17.

Associated congenital malformations:

CH is associated with an increased risk of congenital malformations
  • Extrathyroidal congenital malformations (8.4%): M/C cardiac
  • Other associated malformations: Spiky hair, cleft palate, neurologic abnormalities and genitourinary malformations


Condition of severely stunted physical and mental growth due to untreated congenital hypothyroidism.


Diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests.

CH diagnostic algorithm: Diagnosis of congenital hypothyroidism begins with either abnormal newborn screening test results or a clinical suspicion of hypothyroidism, leading to serum thyroid function tests (typically TSH and free T4) to confirm the diagnosis. If a diagnosis of primary or secondary (central) congenital hypothyroidism is confirmed, other diagnostic studies can be undertaken to determine the underlying aetiology. | Rastogi, M. V., & LaFranchi, S. H. (2010). Congenital hypothyroidism. Orphanet journal of rare diseases, 5, 17.

Newborn thyroid screening tests:

Dried blood sample from a heel-prick collected on special filter paper cards. Specimens routinely collected at 2-5 day age
  • Low free T4 and high TSH: Primary hypothyroidism
  • Normal free T4 (or total T4) and high TSH: Compensated/subclinical hypothyroidism
  • Low free T4 and low/normal TSH: Central hypothyroidism accompanied by other pituitary hormone deficiencies (growth hormone or ACTH deficiency or diabetes insipidus)
Thyroid dysgeneis
Thyroid dyshormonogenesis+
Thyroid receptor blocking antibodies
Central hypothyroidism↓/N

Confirmatory serum thyroid testing

Once an infant has been detected with abnormal thyroid screening tests, they should be recalled immediately for examination, and a venapunctue blood sample should be obtained for confirmatory serum testing. Confirmatory serum is tested for TSH and either free T4 or total T4 combined with some measure of binding proteins, such as a T3 resin uptake.

Thyroid radionuclide uptake and scan:

M/accurate tests in defining some form of thyroid dysgenesis, e.g., an ectopic gland, thyroid hypoplasia (decreased uptake in a eutopic location), or thyroid aplasia
Technetium 99 m scan findings in congenital hypothyroidism. A-Technetium 99 m scan, showing a large gland (approximately twice normal size) in eutopic location, consistent with dyshormonogenesis. B-Technetium 99 m scan, showing uptake in ectopic location, i.e. ectopic gland. C-Minimal uptake, consistent with aplasia or severe hypoplasia. | Rastogi, M. V., & LaFranchi, S. H. (2010). Congenital hypothyroidism. Orphanet journal of rare diseases, 5, 17.

Plain radiography:

Useful in skeletal survey and monitoring of treatment
  • Absence of distal femoral and proximal tibial epiphyses at birth
  • Punctate epiphyseal dysgenesis (multiple foci of ossification)
  • Deformity/beaking of 12th thoracic or 1st/2nd lumbar vertebrae
  • X-ray skull:
    • Large fontanelles and wide sutures
    • Wormian (intrasural) bones
    • Enlarged and round sella tursica


The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter.

Levothyroxine (treatment of choice)

Can prevent intellectual deficits and optimize neurodevelopmental outcomes

T4 first increases after 1 week of treatment and TSH normalises later after 4 weeks

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