Incidence

The incidence of congenital hypothyroidism is 1 in 3000–5000, with some geographical variation.

Aetiology and genetics

Some 75% of cases are due to dysgenesis (agenesis, ectopia), 10% to dyshormonogenesis, 5% to hypothalamic–pituitary deficiency (central hypothyroidism) and 10% to transient hypothyroidism (iodine exposure, maternal antithyroid antibodies, etc.). Although thyroid disease appears to be sporadic in the majority of children born with hypothyroidism, evidence for a genetic component is increasing. Hypothyroidism is familial in up to 2% of cases, and children with congenital hypothyroidism have a higher incidence of associated abnormalities (cardiac, renal, hip dysplasia) than the general population.

Studies in mouse models with congenital defects of thyroid development have provided the basis for molecular genetic studies in humans with congenital hypothyroidism. Mutations have been described in a number of genes, resulting in absent, misplaced, hypoplastic or unresponsive glands (Table 19.2.1). In some instances, a specific phenotype can be recognized, and prognosis is affected. For example, in individuals with the NKX2.1 mutation, neurological outcome is poor despite early thyroxine treatment.

Table 19.2.1 Mutations in genes involved in thyroid development resulting in congenital hypothyroidism

Hypothyroid patients with normally located and normally sized glands have defects in thyroid hormone biosynthesis. Recessive mutations in thyroglobulin, thyroid peroxidase, pendrin (causing Pendred syndrome – sensorineural deafness and hypothyroidism) and sodium/iodide symporter (NIS) genes have been described. Mutations in the TRH receptor gene, TSH β subunit and transcription factors regulating pituitary development have also been described in some individuals with central hypothyroidism.

Clinical picture

Often the condition is subclinical and is detected on routine screening. Clinical features that should be looked for are jaundice, dry skin, a hoarse cry, puffy face, prominent tongue, listlessness, umbilical hernia, hypothermia, bradycardia and failure to thrive.

Investigation results

An unconjugated hyperbilirubinaemia (due to glucuronyl transferase deficiency) is common. A raised level of TSH detected on testing of a heel-prick drop of blood collected on filter paper on day 3–5 of life is seen in primary hypothyroidism.

Management

Confirmatory investigations are needed if the screening tests suggest an abnormality: repeat T₄ and TSH; thyroid scan (showing absent, lingual or increased uptake of radioisotope), X-ray distal femoral epiphysis (absence implying prolonged/prenatal hypothyroidism), and assessment and imaging of the pituitary gland if indicated. Treatment involves commencement of therapy (thyroxine replacement at 8–10 μg/kg daily). Thyroid imaging results for congenital hypothyroidism of varying causes are shown in Figure 19.2.1.

Fig. 19.2.1 Thyroid uptake scan appearances in congenital hypothyroidism. (A) Thyroid agenesis. No functioning thyroid tissue present in the neck or in the usual ectopic sites. (B) Dyshormonogenesis. The radioangiogram reveals relatively increased thyroid perfusion. The uptake of pertechnetate in 20 min is 14% (normal = 2–5%). The thyroid scan reveals a diffuse goitre normally located in the neck. (C) Lingual thyroid. There is no evidence of perfused thyroid tissue in the neck. The thyroid scan reveals a prominent midline lingual thyroid. The uptake of pertechnetate in 20 min is 1% (normal = 2–5%). (D) Normal thyroid. The radioangiogram of the head, neck and upper torso is unremarkable. The uptake of pertechnetate in 20 min is 5% (normal = 2–5%). The thyroid scan reveals a normally located bilobed gland.

Prognosis

Normal intellectual and physical development is likely if treatment is commenced promptly and monitored closely. Overtreatment may result in craniosynostosis.

Prevalence

Between the ages of 1 and 18 years, the prevalence is 1.2%. Acquired hypothyroidism is rare prior to 4 years of age.

Aetiology

The causes in order of frequency are as follows: primary hypothyroidism – chronic lymphocytic, autoimmune (Hashimoto) thyroiditis, late-appearing congenital dyshormonogenesis, exogenous factors (e.g. high-dose iodine exposure (Wolff–Chaikoff effect), radiation) and severe iodine deficiency; and central hypothyroidism – congenital and acquired hypopituitarism.

Clinical picture

The most common presentation is growth retardation and goitre. In addition, the triad of short stature, obesity and mental dullness indicates hypothyroidism until proven otherwise. Growth impairment usually affects mainly the limbs so that body proportions predominantly remain infantile. Other features include hypothermia, bradycardia, slow reflex relaxation, constipation, dry hair and skin, pallor, facial puffiness (‘myxoedema’) and dental delay. The onset is often insidious, with delays of up to 4–5 years being reported between the onset of growth retardation and the diagnosis of hypothyroidism. Although delayed puberty usually occurs, some cases of precocious puberty have been reported.

Autoimmune thyroiditis may be associated with other autoimmune diseases (autoimmune polyglandular syndromes) such as type 1 diabetes, autoimmune adrenalitis (Addison disease), vitiligo and pernicious anaemia. Occasionally, autoimmune hypothyroidism can be preceded by a period of transient hyperthyroidism.