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Congenital hypothyroidism (CH) can be defined as a lack of thyroid hormones present from birth which, unless detected and treated early, is associated with irreversible neurological problems and poor growth.
Some infants may develop a lack of thyroid hormones after birth and this may represent primary hypothyroidism rather than CH. Children with primary hypothyroidism do not experience the irreversible neurological problems that are seen with untreated CH.
- In the UK 1 in 4,000 live births have congenital hypothyroidism (CH).
- The incidence is twice as common in females.
- Areas with iodine deficiency associated with endemic cretinism are Bangladesh, China, Peru and Zaire. This has in part been counteracted by compulsory iodination of salt.
- Italian screening for CH suggests it is more prevalent in multiple pregnancies - the cause of which remains unclear.
- Anatomical defects:
- Accounts for 75% of all cases.
- There may be thyroid aplasia, hypoplasia or ectopic thyroid tissue.
- It is not inherited, so that chances of another sibling being affected are low.
- Disorders of thyroid hormone metabolism:
- This accounts for 10% of cases.
- Examples include TSH unresponsiveness and defects in thyroglobulin.
- This is usually inherited and so there is a risk that further children may also be affected.
- Hypothalamic or pituitary dysfunction.
- Hypothalamic-pituitary dysfunction accounts for 5% of cases of congenital hypothyroidism (CH). Pituitary hypothyroidism usually occurs with other disorders of pituitary dysfunction, eg lack of growth hormone.
- Hypothalamic causes include tumours, ischaemic damage or congenital defects.
- Transient hypothyroidism
- This accounts for 10% of cases and is usually related to either maternal medications, eg carbimazole, or to maternal antibodies. In maternal thyroid disease, IgG auto-antibodies can cross the placenta and block thyroid function in utero; this improves after delivery.
- A number of genetic defects have been associated with CH. This includes mutations in the 'paired box gene 8' (PAX8) and the 'dual oxidase 2 gene' (DUOX2). The PAX8 gene is involved in the development of various tissues in the embryo. PAX8 is particularly linked to the formation of the kidney and thyroid gland. Several mutations of PAX8 are described with varying degrees of thyroid dysfunction. The DUOX2 gene encodes an enzyme called dual oxidase 2 which generates hydrogen peroxide in the thyroid gland, gastrointestinal tract and the lungs. Dual oxidase 2 is crucial to the production of thyroid hormones.
Infants are usually clinically normal at birth due to the presence of maternal thyroid hormones.
- Feeding difficulties
- Low frequency of crying
- Large fontanelles
- Myxoedema - with coarse features and a large head and oedema of the genitalia and extremities.
- Nasal obstruction.
- Low temperature (often <35°C) with cold and mottled skin on the extremities.
- Jaundice - prolongation of the physiological jaundice.
- Umbilical hernia.
- Hoarse voice.
- Pericardial effusion - usually asymptomatic.
- Failure of fusion of distal femoral epiphyses.
- The growing child will have short stature, hypertelorism, depressed bridge of nose, narrow palpebral fissures and swollen eyelids.
- Refractory anaemia.
- A goitre may be present (more likely with dyshormonogenesis, thyroid hormone resistance and transient hypothyroidism).
5% of patients will also have other congenital defects, eg atrial septal defects or ventricular septal defects.
Infants not treated early may have delayed mental development, learning difficulties and poor co-ordination.
- All babies are screened at birth (with their mothers' consent), using blood taken via a pinprick and analysed for TSH and T4. This is part of the UK Newborn Screening Programme (the blood is also analysed for phenylketonuria, cystic fibrosis and sickle cell disease).
- A high TSH and low T4 confirm the diagnosis.
- Infants may need to go on to have thyroid ultrasound scanning and/or thyroid radionuclide scanning.
- Thyroid auto-antibodies are also measured.
- False-positive results are usually due to intercurrent illness and thyroglobulin deficiency.
- Thyroglobulin levels can also be measured - usually total T4 is low with a normal TSH, but free T4 and T3 are within the normal range. This would require no further treatment.
- 20% of infants may only have a slight increase in TSH - these patients need to be observed and TFTs repeated in a few months.
- The aim of treatment is early detection and early thyroid hormone replacement to ensure that infants do not develop irreversible neurological disability.
- Thyroxine hormone replacement with L-thyroxine is given once daily and titrated to TFTs. There is no evidence at present to suggest that higher starting doses of thyroxine have more beneficial effect on outcome compared with standard doses.
- TFTs need to be monitored on a regular basis. The frequency of blood tests can be reduced after the first 2 years of life once adequate replacement is achieved.
- T4 should ideally be kept in the upper half of the normal range.
- Transient hypothyroidism need not be treated unless the low T4 and raised TSH persist beyond 2 weeks. Treatment is usually terminated after 3 to 5 months.
- Regular monitoring of TFTs.
- Cross-sectional reference growth charts should be used to monitor child growth.
- Monitor achievement of childhood milestones.
- Monitor mental development - four areas need to be reviewed: communication and personality behaviour, language ability, motor ability and adaptive behaviour.
The main adverse effects are related to the lack of adequate thyroid hormone replacement leading to hypothyroidism, or excessive thyroid hormone replacement leading to hyperthyroidism.
Hyperthyroidism in infants is exhibited by tachycardia, anxiety and a disturbed sleep pattern.
If congenital hypothyroidism (CH) is detected early in infants and treatment begun, normal development of mental function can occur. If treatment is delayed, spasticity, gait problems and dysarthria and profound mental disability may result.
Poor self-esteem and depression are amongst several factors that lead to a poorer quality of life in patients who have been treated for CH. A high index of suspicion with careful questioning is required to pick up on these aspects.
- The most common cause is lymphocytic thyroiditis. Other causes may be iatrogenic.
- Typically seen in adolescence, but can occur earlier.
- First signs are slowing of growth (often unrecognised) with other typical signs of hypothyroidism, eg skin changes, cold intolerance, sleepiness and low energy.
- Typically, delayed puberty in adolescence, but younger children may have galactorrhoea or precocious puberty.
- Lymphocytic thyroiditis is also known as Hashimoto's autoimmune thyroiditis.
- It is 4-7 times more common in girls than in boys.
- There is a high incidence in children with Turner's syndrome and Down's syndrome.
Other rarer causes include acute suppurative thyroiditis and subacute non-suppurative thyroiditis (de Quervain's disease).
Further reading & references
- Congenital hypothyroidism - Initial Clinical Referral Standards and Guidelines, British Society for Paediatric Endocrinology and Diabetes and UK Newborn Screening Programme Centre (Jan 2013)
- Park SM, Chatterjee VK; Genetics of congenital hypothyroidism. J Med Genet. 2005 May;42(5):379-89.
- Olivieri A, Medda E, De Angelis S, et al; High risk of congenital hypothyroidism in multiple pregnancies. J Clin Endocrinol Metab. 2007 Aug;92(8):3141-7. Epub 2007 May 8.
- Kumar PG, Anand SS, Sood V, et al; Thyroid dyshormonogenesis. Indian Pediatr. 2005 Dec;42(12):1233-5.
- Foo A, Leslie H, Carson DJ; Confirming congenital hypothyroidism identified from neonatal screening. Ulster Med J. 2002 May;71(1):38-41.
- Morin A, Guimarey L, Apezteguia M, et al; Linear growth in children with congenital hypothyroidism detected by neonatal screening and treated early: a longitudinal study. J Pediatr Endocrinol Metab. 2002 Jul-Aug;15(7):973-7.
- Rastogi MV, LaFranchi SH; Congenital hypothyroidism. Orphanet J Rare Dis. 2010 Jun 10;5:17.
- Kempers MJ, Lanting CI, van Heijst AF, et al; Neonatal screening for congenital hypothyroidism based on T4, TSH and TBG measurement: Potentials and pitfalls. J Clin Endocrinol Metab. 2006 Jun 20.
- Nelson Textbook of Pediatrics. 16th Edition. Behrman RE et al. WB Saunder Co. 2000
- Hrytsiuk I, Gilbert R, Logan S, et al; Starting dose of levothyroxine for the treatment of congenital hypothyroidism: a systematic review. Arch Pediatr Adolesc Med. 2002 May;156(5):485-91.
- Yang RL, Zhu ZW, Zhou XL, et al; Treatment and follow-up of children with transient congenital hypothyroidism. J Zhejiang Univ Sci B. 2005 Dec;6(12):1206-9.
- Selva KA, Mandel SH, Rien L, et al; Initial treatment dose of L-thyroxine in congenital hypothyroidism. J Pediatr. 2002 Dec;141(6):786-92.
- van der Sluijs Veer L, Kempers MJ, Last BF, et al; Quality of life, developmental milestones, and self-esteem of young adults with congenital hypothyroidism diagnosed by neonatal screening. J Clin Endocrinol Metab. 2008 Jul;93(7):2654-61. Epub 2008 May 6.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
|Original Author: Dr Gurvinder Rull||Current Version: Dr Hayley Willacy|
|Last Checked: 20/04/2011||Document ID: 1164 Version: 22||© EMIS|