Hypothyroidism

Summary
Congenital
Transient Neonatal Hypothyriodism

Summary

transient disorders of thyroid function are more common than true congenital hypothyroidism (especially in preterm infants)
when TSH levels are elevated treatment with thyroxine (either long or short term) is usually indicated

Congenital Hypothyroidism

In Australia the incidence is 1 in 3000-3500 with some geographic variation.

75% due to dysgenesis
- agenesis
- ectopia
10% due to dyshormonogenesis
- often autosomal recessive
- Pendred's syndrome = peroxidase deficiency associated with sensorineural deafness
5% due to hypothalamic-pituitary (H-P) deficiency
- secondary hypothyroidism
- tertiary hypothyroidism
10% due to intrauterine causes
- iodine exposure
- maternal antithyroid antibodies

Presentation

the usual mode of presentation is by the presence of an elevated TSH detected on the 48-72 hour screen (except in secondary or tertiary disease)
neonates are often subclinically affected and only detected on routine screening
clinical features include:
- dry skin
- hoarse cry
- puffy face
- prominent tongue
- listless
- umbilical hernia
- hypothermia
- bradycardia
- failure to thrive
neonates may also present with jaundice due to an unconjugated hyperbilirubinaemia (glucronyl transferase deficiency)
gene mutations have been implicated in all forms of congenital hypothyroidism and in some cases result in an expanded phenotype including respiratory distress, choanal atresia, renal malformation and mental delay (independent of degree of hypothyroidism)

Investigation

Confirmatory investigations include

T4 and TSH levels
thyroid scan (showing absent, lingual or increased uptake of radioisotope)
X-ray distal femoral epiphysis (absence implying prolonged/prenatal hypothyroidism)
assessment and imaging of pituitary gland, if indicated

Management

Thyroxine replacement therapy should be commenced as soon as possible at a dose of 8-10 microgm/kg/day in a single daily dose. Tablets should be ground up between two teaspoons and mixed with a few drops of milk. This solution should be transferred to a small, plastic feeding spoon and deposited on the back of the tongue immediately prior to feeds.

Prognosis

The prognosis is usually one of normal intellectual and physical development if treatment is commenced promptly and monitored closely. Over treatment may result in craniosynostosis and has been implicated in causing attention deficit hyperactivity disorder.

Transient Neonatal Hypothyriodism

This group of conditions can be subdivided into 4 main categories. Cause and biochemical profiles are listed in the table below.

Transient Hypothyroxinaemia
- low serum T4 levels seen in approx. 50%of infants delivered before 30 weeks gestation
- normal or low TSH levels
- corrects spontaneously over 4-8 weeks
- no treatment required
Transient primary hypothyroidism
- low serum T4 levels and high TSH levels
- seen in approx. 20%of premature infants (incidence increases as gestation decreases)
- usually develops within 1-2 weeks ex-utero and often superimposed upon transient hypothyroxinaemia
- repeated screening cards should be sent on all infants <30wks (test at 48hrs and then again at 28days)
- hypothyroidism may persist for 2-3 months
- treatment recommended
Transient hyperthyrotropinaemia
- rare (1 in 16-19,000 births)
- elevated TSH for 3-9 months before reducing spontaneously
- no treament required but need careful follow-up to exclude partial dyshormonogenesis or ectopia
Low T3/T4 syndrome ("sick euthyroid")
- non-thyroidal illness
  
  T3
  
  T4
  
  TSH
  
  Low T3 syndrome
  
  N
  
  N
  
  Low T4 syndrome
  
  N

- no treament required

Causes and biochemical profiles of transient neonatal hypothyroidism

	Serum levels of		Causes
	T4	TSH
Transient hypothyroxinaemia		N	Immaturity of H-P axis (<30 wks gest'n)
Transient primary			Maternal anti- hypothyroidism thyroid therapy, iodine deficiency, maternal Ab's, idiopathic
Transient hyperthyrotropinaemia	N		Erroneous assay, iodine deficiency or excess, idiopathic
Low T3/T4 syndrome	N or	N	Prematurity, (In preterm infants) surgical stress, sepsis, malnutrition

	T3	T4	TSH
Low T3 syndrome		N	N
Low T4 syndrome			N