Congenital Hypothyroidism

Congenital hypothyroidism (CH) is a condition present at birth where the thyroid gland doesn’t produce enough thyroid hormone. It’s the most common inherited endocrine disorder and, if left untreated, can lead to severe and irreversible neurodevelopmental delay. The UK’s universal neonatal screening program is vital for early detection and treatment.

Pathophysiology and Aetiology

Pathophysiology: Thyroxine ( $T_{4}$ ) is crucial for fetal brain development, with a third of the required amount crossing the placenta from the mother. After birth, a surge in thyroid-stimulating hormone (TSH) occurs in the newborn. If the thyroid gland is dysfunctional, this surge won’t lead to a subsequent rise in $T_{4}$ .
Aetiology: The vast majority of cases in the UK (80-85%) are permanent and caused by thyroid dysgenesis (aplastic, hypoplastic, or ectopic thyroid tissue). Other, rarer causes include defects in thyroid hormone synthesis (dyshormonogenesis), or a temporary form caused by the transplacental passage of maternal antibodies.

Clinical Presentation

Most babies with CH are asymptomatic at birth due to the presence of maternal thyroid hormones. This makes clinical diagnosis unreliable in the first few weeks of life and highlights the importance of newborn screening.

When symptoms do appear, they are often non-specific and subtle:

Feeding Difficulties: Poor feeding, a weak cry, and a sleepy, lethargic demeanour.
Physical Features: Features like a large, protruding tongue, puffy eyelids, and a hoarse cry are classic but often appear later. Other signs can include dry, scaly skin, a wide posterior fontanelle, and an umbilical hernia.
Prolonged Neonatal Jaundice: This is a common early sign of CH.

Diagnosis

Newborn Screening: All infants in the UK undergo a blood spot test (Guthrie card) at 5 days of age. This screens for a number of conditions, including CH, by measuring TSH levels. A positive screen is a high TSH level.
Confirmatory Tests: If the screen is positive or there’s a strong clinical suspicion, a confirmatory venous blood test is performed. The diagnosis is confirmed by a high TSH and a low free $T_{4}$ .
Thyroid Imaging: An ultrasound or radionuclide scan can be used to identify the location of the thyroid gland (agenesis or ectopic tissue) but this is not required for initiation of treatment.

Management

Early diagnosis and treatment are critical for a good neurodevelopmental outcome.

Hormone Replacement: Treatment should start as soon as the diagnosis is confirmed. The standard treatment is levothyroxine replacement, with a starting dose of 10-15 mcg/kg once daily.
Monitoring: Treatment is monitored with regular blood tests (TSH and free $T_{4}$ ). The goal is to keep the free $T_{4}$ in the upper half of the normal range and the TSH in the low-normal range, especially during the first two years of life.
Prognosis: With prompt and adequate treatment, the prognosis for normal growth and neurodevelopment is excellent. Without treatment, children may develop intellectual disability, short stature, and delayed dentition.