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Year : 2013  |  Volume : 10  |  Issue : 2  |  Page : 47-55

Congenital hypothyroidism: Its profile in infancy

1 Department of Paediatrics, Leicester Royal Infirmary, Leicester, United Kingdom
2 Artemis Health Institute, Gurgaon, India
3 Childcare Centre, Katra Bazaar, Shikohabad, Uttar Pradesh, India

Date of Web Publication16-Apr-2013

Correspondence Address:
Vijai Kumar Kapoor
Childcare Centre, Katra Bazaar, Shikohabad, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-0354.110577

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Thyroid hormones play an important role in the physical development, neuronal growth and influence various metabolic processes of the newborn. Their deficiency or a defect in thyroid hormone receptor activity may present as congenital hypothyroidism. This may lead to irreversible mental and physical growth retardation. Interestingly majority of the neonates with congenital hypothyroidism appear to be normal. These facts led us to review this entity in infancy. Therefore, initiation of early treatment becomes essential. Levothyroxine is the drug of choice and its dosage should be adjusted with biochemical hormone assays. The untoward effects of congenital hypothyroidism are largely reversible, if treated before the age of 6 weeks, a very easily affordable help in curtailing the morbidity among these newborns. Genetic counseling and routine examination of siblings is very essential.

Keywords: Congenital hypothyroidism, dyshormonogenesis, FT4-free circulating thyroxine, infancy, neonatal thyroid screening, neonate, T3 - circulating triiodothyronine, T4- circulating thyroxine, TSH - thyroid stimulating hormone, TSHR - thyroid stimulating hormone receptor

How to cite this article:
Kapoor S, Kapoor D, Kapoor VK. Congenital hypothyroidism: Its profile in infancy. Thyroid Res Pract 2013;10:47-55

How to cite this URL:
Kapoor S, Kapoor D, Kapoor VK. Congenital hypothyroidism: Its profile in infancy. Thyroid Res Pract [serial online] 2013 [cited 2022 Dec 5];10:47-55. Available from: https://www.thetrp.net/text.asp?2013/10/2/47/110577

  Introduction Top

Thyroid hormones play a vital role in the normal functioning of various organs of the body including neural growth, neurotransmission, neuronal migration and lamination enzyme induction. It has now been established that there is a close association of thyroid hormones with fetal brain development. Deficiency or inadequate production of the hormone in neonates manifests as congenital hypothyroidism. It is generally believed to have been present at or before birth [1] and has been commonly observed in a large number of the subjects with suspected endocrinopathies met among pediatric age group. [2],[3] Presentation can be with multiple symptomatology, which if not evaluated early results in an irreversible, and a permanent nervous system damage a consequent developmental delay [4] This subsequently leads to physical and mental growth retardation.

Nearly 10% to 15% of neonates present with diagnostic clinical features. [5] At birth symptoms are more evident than signs and majority of children (about 75%) are diagnosed during the first 4 to 6 weeks of life, [2] a phase very crucial for post natal brain development. [6]

  Incidence Top

The incidence has racial and global topographic differences, being highest in Europe 1:3300 and as low as 1:5700 live births infants in Japan with an average of 1:4500 live births in most other parts of the globe. [7] Neonatal thyroid screening in the U.K. has shown a significantly higher incidence of congenital hypothyroidism in Asian families in comparison with non Asians (1/918 in Asians compared 1/3391 with in non Asians) [8] The incidence is lower among African American newborns and higher among Hispanic newborns compared with the rate among white newborns. [9] International studies have revealed that the incidence of congenital hypothyroidism is approximately 1:3500 neonates in iodine sufficient areas. [10]

Systematic neonatal screening for congenital hypothyroidism has important diagnostic and prognostic implication and so is to be done as a routine. [11],[12] The incidence of various thyroid disorders observed in neonatal period has been reported as being 1:4000 for thyroid dysgenesis, 1:30,000 for thyroid dyshormonogenesis, 1:40,000 for transient hypothyroidism and 1:100,000 for hypothalamic pituitary disorders associated with multiple anterior pituitary deficiencies. [4] The exact data for this disease is not available in our country but on the basis of neonatal thyroid screening data the rate may be as high as 1:2640 (much higher than the world wide average of 1:3800) [6],[13] Incidence is higher among low birth neonates, with girls being more affected than boys [4] approximately in a ratio of 2: 1. [3] Heredofamilial incidence has also been observed and genetic basis of these familial cases has been recognized in some but not in all pedigrees. About 10% of neonates with congenital hypothyroids are associated with cardiac and nervous system and eyes anomalies infants may have associated with hearing loss too. An association of congenital hypothyroidism with Hirschsprung's disease has also been reported. [14],[15]

  Ontogeny and Physiology of Thyroid System Top

Thyroid gland develops from two embryological structures, the thyroid diverticulum and the ultimo bronchial bodies during the third or the fourth week of gestation. [16] The thyroid gland arises in the pharyngeal floor and is visible as a midline endodermal thickening in close proximity to the endothelium of the developing heart during the third or the fourth week of gestation. The developing gland descends to the usual location in the neck through the midline, still connected to the pharynx by the thyroglossal duct. In due course, the thyroglossal duct disappears but the cystic remnants may remain there along this developmental tract and form a thyroglossal cyst. During this phase rare ectopic locations of thyroid tissue at the base of tongue (lingual thyroid) or any disruption of the normal developmental pattern may lead to various congenital anomalies. The diverticulum becomes bilobed in due course and fuses with the ventral aspect of the fourth pharyngeal pouch. This can be recognized by the seventh week of gestation. Neural crest derived from ultimo branchial body forms the thyroid medullary cells and produce calcitonin.

The thyroid hormone synthesis usually begins at about twelfth week of gestation with the development of fetal hypothalamic-pituitary-thyroid system. Synthesis of thyroglobulin starts at 4 weeks and iodine trapping starts by 8 to 10 weeks of gestation.

It has been observed that iodine accumulation and synthesis of thyroxine by the fetal thyroid gland starts at eleventh week and by the twentieth week the concentration of TSH rises in fetal circulation, depicting the maturation of hypothalamic pituitary axis. This is followed by rise in thyroxine level. A rise in thyroxine levels and fetal TSH is also observed in preterm neonates. Significant transfer of maternal thyroid hormones to the fetus takes place through the placenta and via amniotic fluid.

Normally the perinatal changes in thyroid hormone secretion take place as an upward sudden rise in the levels of pituitary TSH secretion followed by an increase in the circulating T3 an T4 levels which takes place after birth and later on a fall in TSH secretion during the first week or life due to feedback inhibitory control by increased serum T4 at dual hypothalamic and pituitary level. These changes in thyroid hormone secretion have to be kept in mind while performing the thyroid hormone function tests in pre and full term neonates.

Thyroid hormones are derived from a large iodinated glycoprotein- T9, which after secretion in the thyroid follicle is iodinated on tyrosine residues and later on coupled via an ester linkage. Reuptake of thyroglobulin into thyroid follicular cells allows proteolysis and thus the synthesis of T3 and T4.

All the processes are under genetic control and a few transcription factors i.e. TTF1, TTF2 and fax 8 (Paired Homeobox-8) and HOX3. Mutations of these developmental transcription factors/genes could be responsible for rare causes of thyroid agenesis or dyshormonogenesis. [17]

Pattern of gene involvement and genetic transmission in congenital hypothyroidism.

  Causes of Congenital Hypothyroidism Top

To assess the various causes of congenital hypothyroidism one should ascertain the site of defect, whether it is in the thyroid gland, thyroid regulatory system, due to deficient thyroid hormone receptor activity or due to inborn errors of the thyroid hormone synthesis. It can be classified either as central (pituitary) hypothyroidism or primary hypothyroidism or as transient or permanent hypothyroidism. Majority of cases with congenital hypothyroidism are sporadic in nature with very few being due to inborn errors of thyroid hormone synthesis as dyshormonogenesis. [18]

Permanent hypothyroidism

  1. Thyroid dysgenesis.
    1. Anatomical error - Abnormal placement of thyroid tissue/gland-ectopia
      1. Lingual.
      2. Sublingual.
      3. Suprahyoid.
    2. Developmental error (embryogenic) of thyroid tissue.
      1. Thyroid hypoplasia.
      2. Thyroid agenesis.
      3. Thyroid hemiagenesis.
  2. Inborn errors in thyroid hormone production - Dyshormonogenesis.
    • Disorders of iodide trapping.
    • Disorders of iodide organification.
    • Disorders of iodotyrosine coupling.
    • Deficiency of iodotyrosine deficiency.
    • Defect of thyroglobulin synthesis, storage or release.
  3. Iodine deficiency.
  4. Anomalous pituitary or hypothalamic development.
  5. Failure in synthesis or release or action of TRH/TSH.
  6. Generalized thyroid hormone resistance.
  7. Genetic defects in embryogenesis.
  8. Multiple hypothalamic hormone deficiency.
    • Idiopathic.
    • Familial.

  Thyroid Dysgenesis Top

Developmental defect of thyroid tissue, although sporadic, has been observed in approximately 80 to 90% of the affected neonates, classified as thyroid hypogenesis (25%), ectopia (35%) and agenesis (40%). [4] Its incidence is slightly lower in our country. [2] Etiogenic factors for these are not fully known in majority of cases, but both immunologic factors and genetic predisposition have been speculated. Its association with PAX 8 further strengthens the association of genetic factors in its etiogenesis. Autosomal dominant mode of inheritance with relatively low penetration has been suggested. [19] Mutations affecting transcription factors (TTF1, FOXE-1 PAX8) NKX2-1/TTF-1] TSHR] TSH induced gene are commonly observed in these patients. Mutation of NKX 2-1 has been held responsible for persisting neurological symptoms with congenital hypothyroidism. In about 33% cases no remnants of thyroid tissue can be detected on sensitive radionuclide scan and in the remaining 67%, rudiments of thyroid tissue may be seen in an ectopic location.

  Dyshormonogenesis Top

Dyshormonogenesis due to faulty metabolism of iodine trapping, iodine organification (peroxidase enzyme), iodotyrosine coupling and synthesis of thyroglobulin or defects may occur in just about any step of thyroid hormone synthesis. This class represents about 10-20% of newborns with congenital hypothyroidism. [18] In our country it is about 4 to 8% and has an autosomal recessive manner of inheritance. Its incidence is slightly higher in our country possibly due of a higher incidence of consanguinity. [6]

  Hypothalamic-Pituitary Dysfunction Top

Hypothalamic-pituitary dysfunction due to anomalous pituitary/hypothalamic development which leads to TRH or TSH deficiency is rare and is seen in 1:30000-500000 births. [17] In UK it is still rarer and has been observed in 1:100000 births causing multiple pituitary deficiencies. Affected children present with hypoglycemia, persistent jaundice, micropenis associated with septooptic dysplasia, midline cleft lip, midface hypoplasia along with other midline facial defects. [17] Some of these cases are even missed on neonatal thyroid screening and thus a vigilant approach of a pediatrician or an endocrinologist is very important. Genetic counseling of parents of these neonates is mandatory. [6]

  Thyroid Hormone Resistance Top

Resistance to thyroid hormone causing generalized tissue resistance, and extra or isolated pituitary resistance are rare. Inheritance is autosomal recessive. Genotype may be homozygous or compound heterozygous. Mutations in thyroid hormone receptor gene have been observed. [17]

  Transient Hypothyroidism Top

Transient hypothyroidism is usually detected on neonatal thyroid screening and generally shows a complete and spontaneous remission in majority. It can be due to.

  1. Iodine deficiency - biochemical hypothyroidism
  2. Prenatal or neonatal exposure to iodides or use of antiseptics containing iodine.
  3. Perinatal stress affecting neonate -birth asphyxia, respiratory distress, neonatal sepsis.
  4. Prenatal consumption of antithyroid drugs or goitrogens.
    1. Drugs
      • Carbimazole, methimazole.
      • Amiodarone.
      • Propylthiouracil.
      • Dopamine.
      • Glucocorticoids.
      • Administration of iodide containing radiographic contrast media.
      • Lithium carbonate.
    2. Goitrogens.
      • Cabbage.
      • Rape seeds.
  5. Detection on neonatal thyroid screening.
    1. Hypothyroxinemia.
    2. Hyperthyrotropinemia.
    3. Primary hypothyroidism.
    4. Low T3 syndrome.
    5. Transplacental transfer of maternal antibodies.
  6. Chromosomal disorders: Down's syndrome.
  7. Congenital nephrosis.
  8. Associated with metabolic diseases.
  9. Transient dyshormonogenesis.
  10. Idiopathic primary hypothyroidism.
In true transient congenital hypothyroidism, a moderate elevation of thyroid stimulating hormone (TSH) level (<40mU/L) along with low T4 levels are observed on thyroid screening of neonates. It normalizes within 4 to 6 weeks, [20] but may persist up to the age of 1 year in 5-10% of children. [21] Different studies have reported incidences varying from 36% to 50%. [22] Frequency of transient hypothyroidism is ten times higher in very low birth weight babies VLWB (infants weighing <1500 g and predominantly premature) [23] compared to low birth weight babies LWB (infants weighing less than 2500 g) [23] where it is four times higher than full term babies. [20]

  Symptomatology Top

About 10 to 15% of the neonates with congenital hypothyroidism present with minimal or no clinical evidence of thyroid hormone deficiency at birth and are thus usually difficult to diagnose in neonatal period or even during the first three months of life, as often sign and symptoms are non specific. [6] Generally, the manifestations of hypothyroidism are observed earlier in those with aplasia as compared to those with ectopic thyroid glands. [24],[25] The symptomatology of congenital hypothyroidism depends upon the underlying etiology as well as the duration and severity of TSH deficiency and impairment of thyroid functions before birth. Clinical awareness of symptoms and a high index of suspicion are very important. The diagnosis of these subjects is to be confirmed by neonatal thyroid hormone screening. This may also help us to define the incidence of thyroid dysgenesis, thyroid biosynthetic defects, dyshormonogenesis, hypothalamic pituitary hypothyroidism, hypothyroxinemia, transient primary hypothyroidism, idiopathic transient hypothyroxinemia and low T3 syndrome in certain undernourished newborns and premature babies. Neonatal thyroid screening is mandatory for low birth premature and critically ill infants and should be done on day second to fifth of birth with a venous sample for FT4/T4 and TSH estimation. Unequivocal TSH elevation >30 mu/L is usually observed with congenital hypothyroidism. If TSH level is less than 30 mu/L with normal FT4 (T4) without clinical features, the baby should be kept under observation for 1 week.

Most hypothyroid neonates are postmature, large and asymptomatic at birth even in the complete absence of thyroid tissue. Symptoms usually appear during the first 4 to 6 weeks of life and about 70% cases are diagnosed in the neonatal period. In the present scenario pediatricians mostly depend upon on the assessment of thyroid screening along with symptomatology. If the facility for thyroid screening is not available one can make the use of Apgar score devised for this purpose along with clinical findings and biochemical studies.

Presenting symptoms may differ at different points in time.

  0 to 4 Weeks (Neonatal Period) Top

  • Slightly increased head circumference.
  • Prolonged physiological hyperbilirubinemia.
  • Poor suckling ability.
  • Sluggish appetite.
  • Hypothermia.
  • Large posterior fontanelle.
  • Abdominal distension.
  • Noisy respiration.
  • Edema all over body.
  • Respiratory distress.
  • Hypotonia.
  • Reduction in stool frequency.
  • Peripheral cyanosis and mottling.

  Fifth Week to Third Month Top

  • Failure to gain weight.
  • Constipation.
  • Generalized edema, more over genitals.
  • Very low pitched prolonged cry.
  • Umbilical hernia.
  • Little perspiration.
  • Protrusion of broad tongue with a wide open mouth.
  • Deposition of fat over clavicles.
  • Low amount of lacrimation.
  • Dark sallow skin.
  • Subnormal body temperature.
  • Appearances of these symptoms are also directly related to the severity of the deficiency of thyroid hormone.

  Fourth Month to Twelve Month (Infancy) Top

  • Hypotonia.
  • Macroglossia.
  • Dry sallow skin.
  • Short neck.
  • Hands are broader with shorter fingers.
  • Poor growth of hairs & nails.
  • Subnormal body temperature.
  • Edema over genitals and extremities.
  • Protrusion of abdominal wall and umbilical hernia.
  • Lethargy.
  • Puffiness of eyes.
  • Delayed closure of fontanelles.
  • Delayed eruption of deciduous teeth.
  • Bridge of nose is depressed and eyes appear far apart.
  • Delayed milestones e.g. holding of head, sitting standing with support.
  • Cardiomegaly.
  • Muffled heart rounds.
  • Asymptomatic pericardial effusion.
  • Delayed relaxation while eliciting deep tendon reflexes.
  • As they grow about 75% to 85% of children show constipation, delayed milestones and retardation of growth as minimal features. [6]

  Diagnostic Evaluation Top

In majority, clinical history including family history of thyroid disease may be present. A detailed obstetric history with a special record of duration of pregnancy is important as prolonged pregnancies extended for more than 2 weeks beyond term have been observed in a large number of cases. A prolonged duration of pregnancy supports the theory that a lack of thyroid hormones in fetus prevents the onset of uterine contractions. [24] Family history should be carefully elicited as an association of maternal hypothyroidism with transient hypothyroidism and paternal hypothyroidism with primary hypothyroidism has been observed in some of these subjects. [9] Signs and symptoms provide clues but neonatal thyroid screening is required to confirm the diagnosis. Many clinical scores in are in practice, but we assess our cases where 2 score points are given to each for umbilical hernia, typical edematous facies and constipation, while one point each is given to wide open posterior fontanelle, pallor, hypothermia, hypotonia, prolonged neonatal icterus, rough dry skin, macroglosia and a large flabby baby (wt > 3.5 kg) Any five points calculated among these are to be considered for congenital hypothyroidism. Main objective of newborn screening of the babies is an early detection of the condition and to prevent mental retardation. Though, screening should be mandatory for every newborn, it may not be feasible in developing countries due to financial constraint.

  Investigations Top


For newborn screening, TSH alone or TSH and total T4 in dried blood spots are obtained in the first 72 h of life. While in preterm or critically ill neonates we estimate till the 7 days of age by heal prick or cord blood obtained from placental end. If the results are suspicious for hypothyroidism they are later confirmed when serum TSH levels are above and FT4 levels are below the age related reference ranges. In North America T4 estimation is being done first and if the T4 values are low TSH estimation is made, while in most part of Canada, Europe and Japan, primary estimation of TSH is made and if it is high further measurement of T4, is done but both these systems have their own merits and demerits. It is better to estimate TSH and T4 levels at first screening. False positive case ratio is observed to be between 2 and 3:1. It is seen in very such neonates or in those who have received blood transfusion. It becomes important to keep in mind that postnatal thyroid function in preterm babies is qualitatively similar but quantitatively reduced as compared to that of full term infants. This is due to immaturity of the hypothalamic- pituitary- thyroid axis and loss of maternal contribution of thyroid hormone. [26]

Before assessing the results of newborn screening, medical staff must be familiar with normal physiological variations in thyroid hormones soon after birth. There is a sudden rise in pituitary TSH secretion (60 to 80 mu/me) within half an hour of birth, which triggers a 2 to 6 times increase in T4 and T3 level by the first day of life. The observed range of T4 (15 to 191 ug/dL) and T3 (up to 300 ug/dL) later on slow decline of TSH (<8 mu/L) level over 5 to 7 days of life. While interpreting the result of screening, gestational age, age of newborn, birth weight and presence of illness, if any should also be considered.

Among full term babies with congenital hypothyroidism normal serum values for T4 is <10mcg/dL and for TSH is >20 miu/mL. Abnormal screening results can be interpreted as

Low levels of T4 with elevated level of TSH

Primary congenital hypothyroidism which may be

(a) Permanent congenital hypothyroidism/
  • Thyroid dysgenesis 80-90%.
  • Dyshormonogenesis 10-20%.
(b) Transient congenital hypothyroidism observed with.
  • Excess iodine exposure to the mother during pregnancy.
  • Maternal iodine deficiency.
  • Transplacental passage of anti thyroid antibodies.
  • Usage of anti thyroid drugs and dietary goitrogens during pregnancy.
(B) Low T4 and normal TSH
Congenital thyroid binding globulin deficiency.
Hypothyroxinemia of the newborn, seen usually in low birth weight infants.
Hypopituitary hypothalamic hypothyroidism.

(C) Normal T4 and elevated TSH
Transient or permanent mild congenital hypothyroidism.
Delayed maturation of hypothalamic/pituitary axis.
Thyroid hormone resistance.
Down syndrome.

(D) Persistent Elevated TSH (6 to 10 mu/L)
Recheck of TSH, T4 and FT4 within 2 weeks - If persistently elevated TSH (>10 mu/L) - congenital hypothyroidism

(E) Low T4 with delayed increase of TSH elevation
Associated with low birth weight or very low birth weight, preterm and very sick newborn.

Sometimes interpretation of neonatal screening values can be quite challenging due to various physiological and pathological influences during this period. It is to be remembered that in babies with a normal thyroid function TSH levels at birth may be high (8 to 20/uU/ml) and T4 & T3 levels may be low, however in the next 30 to 60 min thyroid hormone levels are at a lower level in preterm babies and the TSH level rises further (90 to 160/uU/ml) and is then followed by a rise in T3 and T4 levels by the first 2 days of birth. Within 3 days, TSH levels decline to normal range and in the next 3-4 weeks T4 and T3 remain high and maintain a higher level throughout infancy. If high levels of TSH and low levels of T4 are observed, an urgent blood sample for serum TSH, free T4 and thyroglobulin should be drawn to confirm the diagnosis of primary hypothyroidism. Serum thyroglobulin levels are usually low in neonates with thyroid agenesis or defective synthesis or secretion of thyroglobulin and higher in those with ectopic glands and in those with inborn errors of thyroxine synthesis. Hypothyroid mothers should also be checked for the presence of TSH receptor blocking antibodies in serum. In cases where T4 level is low and TSH level is normal, thyroxine binding-globulin levels should be estimated to diagnose central hypothyroidism or thyroxine-binding protein abnormality. [27] Even in the absence of symptoms, estimation of T4 and TSH concentration from capillary blood is to be done between day 2 and day 5 of birth. In our country however, it may be more viable to have TSH screening only. [6] Pediatrician should be aware about hypothyroidism causing morbidity despite normal findings on neonatal thyroid screening. Joint Guidelines of American Academy of Pediatrics, American Thyroid Association and Lawson Wilkins Pediatric Endocrine Society may serve as guides for the initiation of therapy. [28] It is worth while to mention that special attention should be given during neonatal screening for identical twins and it is mandatory to do screening in those with maternal history of thyroid medication or family history of congenital hypothyroidism and it should be performed on cord blood. [29] It has also been observed that few babies show normal values on first screening and develop hypothyroidism later (1: 30000) and it is detected on re-screening. [30] Screening should also be done in cases suspected of having hypothyroidism, in those with thyroid disease in mother especially during pregnancy, family history of thyroid dyshormonogenesis and chromosomal defect such as Down syndrome.

Ultrasonography and isotope scanning

Thyroid ultrasound scanning is a sensitive diagnostic tool for identifying the location of thyroid tissue in neck. The absence or reduction in gland size suggests thyroid dysgenesis. Thyroid ultrasonography may also demonstrate an enlarged or an absent gland. Large thyroid gland may be seen in inborn errors of thyroid hormone synthesis or due to disease produced by maternal TSHR auto antibodies.

Role of isotope scanning in babies with congenital hypothyroidism is controversial. 99 m technetium or 123 I- labeled sodium iodide scan can provide information about the location and the site of the thyroid gland and also help in distinguishing between thyroid dysgenesis and dyshormonogenesis with goiter. However, data should be interpreted with caution and is not to be recommended for routine practice. Thus, radionuclide imaging and ultrasonography play a vital role in early diagnosis and are complementary to each other. [13] 123 I uptake, per-chlorate discharge test, serum/salivary/urine Iodine levels and estimation of serum T4 precursors are of great help to find out certain inborn errors of thyroid hormone synthesis. These tests are employed for the detection of dyshormonogenesis. At the end of 1 h, 60 to 70% of perchlorate is discharged in those with peroxidase deficiency while less than 10% discharge is seen in normal babies. In certain cases, maternal and neonatal serum thyroid antibodies determination may be needed to confirm autoimmune thyroid diseases and urinary iodine measurement for suspected iodine exposure or deficiency may be done.


Epiphyseal dysgenesis on radiograph of the knees is virtually pathognomonic in these subjects. It may reveal an absence of distal femoral epiphysis and proximal tibial epiphysis or absence of cuboid epiphysis.

In a full term normal- weight baby epiphyses often show multiple foci of ossification deformity of twelfth thoracic or first and second lumbar vertebra.

X-ray chest may show cardiomegaly because of an underlying pericardial effusion.

X-ray skull may show large fontanelle with wide sutures and a poorly developed base. Thyroid hypoplasia can produce an enlarged and a rounded sella turcica, intrasutural bones (Wormian Bones) are also common. Delayed formation of dental buds, widely set orbits, an fatten and short nasal bone may also be observed.


E.C.G. may show a low voltage P and T waves with diminished amplitude of QRS complexes indicating poor left ventricular function and pericardial effusion.


Echocardiography may be done to confirm pericardial effusion.


This often shows low voltage recording.

MRI/CT scan

This is usually normal before treatment, although proton magnetic resonance spectroscopy shows high level of choline containing compounds, which can reflect blocks in myelin maturation. [26]

CT or MRI brain may also be done in suspected cases of central hypothyroidism to exclude an underlying organic pathological cause. Chromatography and studies of thyroid tissue to assess the nature of the defect.

Genetic studies

Genetic studies may be done to determine the defects in the steps along the thyroxine bio synthetic pathway (See pattern of gene involvement).


The aim of the management is to normalize T4 within 2 weeks and TSH within 4 weeks. TSH level should be maintained between 0.5 to 2.0 mu/L during first year of life. [30],[31] Levothyroxine sodium is the drug of choice and can be started in a dose of 10 to 15 mcg/kg/day. Infants with severe hypothyroidism (where serum T4 <3 mg/dL or TSH >40) should be started with higher end dose. The medication should be first thing in the morning. The tablet can be crushed in breast milk or any other liquid and is to be administered as a single daily dose, [22],[32],[33] regularly at a fixed time at least 30 min before feeding. [33],[34] Recently, a new preparation of T4 in drops has been made available in several parts of the globe. [10] Doses need not be adjusted in case of a coexistent illness or with a co prescribed drug. The adverse effects of prenatal hypothyroidism are largely reversible if treated before 6 weeks of age. The clinical impact of hypothyroxinemia with normal TSH levels frequently seen in preterm infants usually resolves within the first 8 weeks of life. Simultaneous use of iron, calcium and soya bean preparation should be avoided as they interfere with the absorption of sodium levothyroxine. [35],[36],[37] In case of soya preparations being required for infants with galactosemia, hereditary lactose deficiency, lactose intolerance or when breast feeding or cow milk based formulas are not able to bring nutritional need of the infant, dose of the drug should be adjusted according to clinical response. Frequent monitoring and follow up along with higher dose of levothyroxine may be required. Constant careful biochemical monitoring of these babies is mandatory and thyroid functions should be on the seventh, fourteenth, and twenty-eighth day of therapy, till they normalize and then at monthly intervals up to the age of 3 month and then every 2 to 3 months thereafter. If the child develops irritability, diarrhea or tachycardia during this period further adjustment of the dose may be required. Fortunately these symptoms are rare. Serum T4 should be maintained in the age related upper range of normal along with a normal TSH. In certain cases of altered sensitivity of the hypothalamic pituitary axis, the TSH level may remain high with the T4 in the upper range of normal for age. In these cases, a higher dosage is not required. The adjustment of dose depends upon the clinical response of serum FT4 and TSH levels and during the course of treatment total T4 or FT4 should be in the upper half of the reference level of the age with low serum TSH. [29] In the latter half of infancy a dose of 6 to 8/ug/kg/day is adequate and dose adjustment is done according to plasma iodothyronine concentration. Excessive use of drug (as demonstrated by suppressed TSH) for prolonged period should be avoided as it may increase the risk of craniosynostosis, advanced bone growth which may lead to deceleration in linear growth, temperamental problems (hyperactivity) brain dysfunction and osteoporosis. [3] Biochemical tests should also be used as a guideline to assess developmental progress, physical growth and intellectual function.

Prognosis and follow-up

Early clinical detection in association with neonatal screening and an early initiation of therapy has shown a dramatic change in the prognosis. Congenital hypothyroidism is associated with persistent morbidity in many aspects of cerebral function. The final outcome of these neonates is directly related to the nature and the severity of thyroid abnormality, the underlying causative factor and the time elapsed in starting the supplementation of the drug. The condition is one of the few disorders where infants are at a great risk of irreversible and permanent neuron-development impairment and developmental retardation. It can cause sensorineural hearing impairment, speech delay, memory impairment and motor skills are delayed if not treated early. These children have an immature thyroid system and are hence more prone to thyroid dysfunction. Pediatricians, family physicians, trained and educated primary health workers should be aware of these aspects of the disease and should make an effort for early diagnosis and rapid correction of hypothyroidism, which may help these babies to achieve a normal I.Q. and improve the ultimate outcome. Follow-up of these babies should include developmental progress, physical assessment, which includes monitoring of height and weight in particular and growth in general.

The best prognosis has been observed in infants with persisting ectopic thyroid gland and poorest among the subjects with defective organic binding of iodide. [38],[39]

  References Top

1.Wilkins L. The diagnosis and treatment of endocrine disorder in childhood and adolescence. 3 rd ed. Springfield, Illinois: Thomas; 1965. p. 93.  Back to cited text no. 1
2.Raine JE, Donaldson MD, Greqory JW, Savage MO, Hintz RL. Practical Endocrinology and Diabetes in Children. Black well publishing- Thyroid disorders. 2 nd ed. India: Panther Publishers Private Limited; 2006.p. 95-8.  Back to cited text no. 2
3.Desai MP, Bhatia V, Menon PS. Pediatric endocrine disorders. The thyroid disorders New Delhi: Orient Longman Ltd; 2001. p. 183-99.  Back to cited text no. 3
4.Bettendorf M. Thyroid disorders in children form birth to adolescence. Eur J Nucl Med Mol Imaging 2002;29 (Suppl 2):s439-46.  Back to cited text no. 4
5.Desai MP. Hypothyroidism, Goiter and Thyroid Neoplasia. Pediatrics Endocrine Disorders, 2 nd ed. New Delhi: Orient Longmann Pvt. Ltd; 2008.  Back to cited text no. 5
6.Meena P. Desai - disorders of thyroid gland in India. Indian J. Pediatr 1997;64:11-20.  Back to cited text no. 6
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