Congenital Hypothyroidism

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Diagnosis and reasoning

Neonatal jaundice is extremely common, and very often, physiological in origin. However, it may also herald the presence of severe pathology - thus a careful examination should be performed in all patients. Examination of this neonate shows one sign out of the ordinary - the presence of abnormally wide fontanelles. This alone is sufficient to encourage further evaluation (note that the liver is usually palpable at this age - thus the 1 cm subcostal expanse is not significant). At this point, estimation of serum bilirubin levels is the investigation of greatest value. This will allow determination of whether the jaundice is direct or indirect, significantly narrowing down the differential diagnosis. In this patient, the direct bilirubin fraction is less than 20% of the total bilirubin, i.e. this is indirect (unconjugated) hyperbilirubinemia. The commonest cause of indirect hyperbilirubinemia in the newborn is hemolysis. This is easily detected by a full blood count with a blood film. In this patient, the hemoglobin level is normal, the reticulocyte count is not elevated (a value of 2.5% to 6.5% is normal in newborns) and the blood film shows no evidence of hemolysis. Relatively few other diseases cause indirect hyperbilirubinemia: mainly congenital hypothyroidism (CH), Gilbert syndome, and a few rare conditions such as Crigler-Najjar syndrome and transient familial neonatal hyperbilirubinemia. Note also that infants with galactosemia or fructosemia may exhibit indirect hyperbilirubinemia during the first week of life. CH impairs bone maturation, resulting in delayed closure of the fontanelles - making it the diagnosis most compatible with the examination findings. A thyroid profile is probably the next investigation indicated. His TSH level is markedly elevated - this is compatible with CH, but not diagnostic as there may be a temporary surge in TSH during the first few days of birth. Thus, the thyroid profile should be repeated at around 1 to 2 weeks of age in order to confirm the diagnosis. Note also the low normal T4 level. While counter-intuitive at first glance, this is still compatible with CH, as passage of maternal T4 via the placenta may result in temporary elevation of hormone levels. Phototherapy is important in his management - this will convert the unconjugated bilirubin into water soluble photo-isomers, facilitating excretion. Thyroxine supplementation should only be commenced following the confirmatory test. Radioiodine should not be administered to neonates. IV immunoglobulins are a therapeutic option in hemolytic disease of the newborn.


CH is defined as thyroid hormone deficiency present at birth. The incidence is estimated at around 1 in 4000 births, with females affected almost twice as often as males. It is an important treatable cause of mental retardation. CH may be further classified into primary CH (due to a defect in the gland itself) and secondary CH (due to a deficiency of TSH). Primary CH is more common, and may be due to a problem in the development of the thyroid gland (dysgenesis), due to a disorder in the biosynthesis of thyroid hormones (dyshormonogenesis) or due to endemic cretinism (in certain geographic areas). Pendred syndrome (an autosomal recessive disorder characterized by sensorineural hearing loss and thyroid dyshormonogenesis) is a rare primary cause of CH. Secondary CH typically occurs as a component of congenital hypopituitarism. In addition, CH may occur in a rare transient form, where the child is hypothyroid at birth, but reverts to an euthyroid state within the first few months to years of life. The most common symptoms found in CH are prolonged jaundice, lethargy, difficulty in feeding and constipation. In addition, these babies are quiet, may sleep through the night and may have a hoarse cry. The antenatal history may contain clues such as a gestation beyond 42 weeks, maternal autoimmune thyroiditis or an iodine deficient diet. On examination, the most common signs are are an umbilical hernia, macroglossia and cold or mottled skin. A posterior fontanelle wider than 0.5 cm may be noted, while a goitre may be noted in patients with dyhormonogenesis (secondary to overstimulation by the high TSH levels). Overall, prolonged jaundice, poor feeding, and a wide posterior fontanelle are the most striking clinical features of CH. In addition, neonatal jaundice persisting beyond three weeks of life should always raise the suspicion of CH. Note that these clinical features develop over time - they may be very subtle or even completely absent at birth. Because of this (and because of the profound implications of missing the disease), routine screening of all newborns is performed in many countries. Screening is typically performed between 2 to 5 days after birth. A sample of capillary blood is collected from a heel stick and absorbed onto filter paper, following which TSH and/or T4 levels are estimated. If the screening test is positive, a confirmatory test is performed at around 1 to 2 weeks of life. Unfortunately, almost two-thirds of newborns worldwide are not screened (especially in the developing world) - thus clinicians should maintain a high index of suspicion for the disease. Further investigations such as radionuclide uptake scanning, ultrasound scans and genetic studies may be undertaken to identify the causative etiology. However, these are of limited use in the subsequent management. Once diagnosed, thyroid hormone replacement therapy should be commenced as soon as possible (ideally, within the first 3 weeks of life), with the aim of restoring clinical and biochemical euthyroidism. The timing is crucial because there is an inverse relationship between the intelligence quotient (IQ) and the age of onset of treatment. Of note, treatment should be initiated in all infants with a positive screening result, immediately after confirmatory tests are drawn (and before results are available). These patients should be followed up regularly during the first three years of life, as hormonal requirements increase as the child grows. Clinical evaluation, measurements of serum T4 and TSH and evaluation of bone age are of use in determining how to adjust or increase the dose. In addition, education of the parents in this regard is extremely important, as is obtaining up to date contact details to facilitate compliance. In the long term, all patients will have permanent hypothyroidism (except the rare few with transient deficiencies), mandating lifelong replacement therapy.

Take home messages

  1. CH is an important treatable cause of mental retardation worldwide.
  2. The diagnosis is easily missed, as very few clinical findings are present at birth.
  3. In infants with a positive screening result, replacement therapy should be initiated immediately after confirmatory tests are drawn.
  4. Regular followup is important, as hormonal requirements increase with age.
  5. Almost all patients will require lifelong replacement therapy.

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  1. American Family Physician 2009 : Screening for Congenital Hypothyroidism - U.S. Preventive Services Task Force Reaffirmation Recommendation Statement
  2. Archives of Disease in Childhood 1992, Grant DB, Smith I, Fuggle PW, Tokar S, Chapple J: Congenital hypothyroidism detected by neonatal screening: relationship between biochemical severity and early clinical features.
  3. Clinical Endocrinology (Oxf) 2008, Mathai S, Cutfield WS, Gunn AJ, Webster D, Jefferies C, Robinson E, Hofman P: A novel therapeutic paradigm to treat congenital hypothyroidism.
  4. Molecular Genetics and Metabolism 2007, Harris KB, Pass KA: Increase in congenital hypothyroidism in New York State and in the United States.
  5. Orphanet Journal of Rare Diseases 2010, Congenital hypothyroidism, Maynika V Rastogi, Stephen H LaFranchi