Hypothyroidism

Epidemiology

Congenital hypothyroidism affects around one in 2000 to one in 4000 live births each year (1,2) although improved numbers and sensitivities of screening programs means that the incidence rate is actually rising.

Pathophysiology

There are two main causes of congenital hypothyroidism: Thyroid dysgenesis and thyroid dyshormonogenesis. Because of these abnormalities most congenital hypothyroidism cases are primary, isolated and permanent (4).

Thyroid dysgenesis

Thyroid dysgenesis is a developmental abnormality of the thyroid gland. Either it doesn’t develop at all (agenesis) or it is poorly formed and may be ectopic (dysgenesis) (3).

It accounts for around 85% of causes (1,2). Because of this dysgenesis, most congenital hypothyroidism cases are primary, isolated and permanent.

Thyroid dyshormogenesis

This is a less common cause with an anatomically normal thyroid gland. An enzymatic defect means the thyroid is unable to produce thyroid hormone normally. This accounts for the remaining 15% of cases (5).

Risk 

• Female
• Prematurity
• Low birth weight
• Twins (as they are often premature and have a low birth weight) (1)

Clinical features

Due to the successful implementation of screening programmes worldwide, congenital hypothyroidism is usually picked up in babies when they are asymptomatic. This has led to a marked decreased in the complications and detrimental effects of late diagnosis and treatment in paediatric patients (5,6).

Symptoms and signs can vary significantly, therefore it is very important to take a thorough history and examination.

Common symptoms and findings in history: 

• Feeding difficulties
• Lethargy and increased sleeping
• Constipation
• Prolonged jaundice
• Hoarse cry (1,2,5)

Common signs on examination: 

•  Poor growth
• Macroglossia
• Myxedema
• Large fontanelles
• Hypotonia
• Bradycardia
• Distended abdomen with umbilical hernia
• Goitre (1,2,5)

Hypothyroidism may be picked up on later in childhood, either because of symptoms or through screening programmes for other autoimmune diseases (e.g T1DM) (3).

Differential diagnosis

If newborn screening detects congenital hypothyroidism and thyroid function blood tests confirm this then there is no need to consider a differential diagnosis.

If not picked up at birth, the signs and symptoms of congenital hypothyroidism can be slow to develop, and many are non-specific. This makes diagnosis more challenging as the symptoms could be caused by a wealth of other conditions (2). The process here would be to rule out other conditions that may be causing the symptoms and eventually, the correct diagnosis should be made.

Investigations

Screening

All newborn babies in the UK have a screening test for congenital hypothyroidism. This is usually done between the 5^th and 8^th day of life (3).

Diagnosis

Diagnosis of congenital hypothyroidism is very similar to the process for acquired hypothyroidism in older children and adults.

A series of laboratory blood tests are undertaken to confirm inadequate thyroid function. These include:

• Serum TSH (thyroid stimulating hormone)
• Free T4 (thyroid hormone)

Most commonly, serum TSH levels are raised, to try and compensate for low levels of thyroid hormone circulating in the body and are the first detectable abnormality. Therefore TSH is the most sensitive test for the diagnosis of congenital hypothyroidism (5).

Other tests

• Imaging can be undertaken to identify placement and activity of the thyroid gland. These include either ultrasound and/or radioisotope scans to find potential causes.
• An auditory assessment is done as hypothyroidism may be associated with sensorineural deafness and is done as routine shortly after birth in the UK (3).

Management

Initial management

Levothyroxine should be started immediately to replace the missing thyroid hormone.

Definitive and long-term management

Lifelong levothyroxine replacement therapy will often be required, alongside regular monitoring of growth, neurodevelopment and thyroid function, particularly during the first 2 years of life. After this, monitoring is required less frequently (6).

Some children have transient hypothyroidism and may not require further treatment after the first 2 years of life. If a permanent form of hypothyroidism has not been identified, the child can be trialed off levothyroxine at 2 – 3 years of age to decide if lifelong treatment is required (6).

Complications

Late diagnosis and delayed treatment can lead to impaired neurocognitive development and growth (5).

The risk of neurocognitive complications is significantly reduced if early diagnosis and treatment is started within first two weeks of life (3).

Prognosis

Prognosis is good if the patient is started on appropriate treatment and adheres to it well, giving them a life expectancy similar to the general population (5).

References