Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

80

12. What are the causes of permanent congenital hypothyroidism?

The most common cause of permanent congenital hypothyroidism is thyroid

dysgenesis (85 %) followed by dyshormonogenesis (10–15 %) and rarely,

central hypothyroidism. Thyroid dysgenesis is commonly sporadic, although

2 % are familial. However, thyroid dyshormonogenesis is inherited as an auto-

somal recessive disorder.

Disorders Etiology Pathogenesis

Thyroid dysgenesis TTF-1, TTF-2, PAX-8, FOXE1,

NKX2.1, and TSH receptor gene

mutations

Defect in thyroid

transcription factors which

are required for growth,

development, and migration

of thyroid gland

–Thyroid agenesis

–Thyroid hypoplasia

–Ectopic thyroid

Dyshormonogenesis Sodium–iodide symporter, thyroid

peroxidase (TPO), pendrin,

DUOX1/DUOX2 and

thyroglobulin, iodotyrosine

deiodinase gene ( DEHAL1 )

mutations

Defective thyroid hormone

synthesis

Central hypothyroidism HESX1, LHX3, LHX4, PIT1,

PROP1 gene mutations

Defective TRH–TSH axis

TSH-β gene mutations

TRH receptor gene mutations

13. What are the clinical features of congenital hypothyroidism in a newborn?

The clinical manifestations are commonly subtle in newborns with congeni-

tal hypothyroidism (CH). Newborns with CH may be asymptomatic because

of presence of maternal T 4 (which contributes to approximately one-third of

circulating T 4 in a newborn) and residual functioning thyroid tissue. The

classical symptoms of congenital hypothyroidism include lethargy, hoarse

cry, feeding diffi culty, constipation, and increased somnolence. The charac-

teristic signs of CH include prolonged neonatal jaundice, macroglossia,

umbilical hernia, wide posterior fontanelle, hypotonia, dry skin, and hypo-

thermia. Twenty percent of neonates with CH have history of postmaturity

(>42 weeks). Birth length is normal, while birth weight may be >90th percen-

tile. Presence of goiter points to a clinical diagnosis of thyroid dyshormono-

genesis, whereas absence of goiter suggests thyroid dysgenesis; however it

does not rule out dyshormonogenesis. In addition, oral cavity should also be

carefully examined for lingual thyroid. Deafness may be present in newborns

with CH as an association with congenital hypothyroidism or as a manifesta-

tion of Pendred syndrome. Delayed bone age is a characteristic feature of

CH, as evidenced by the absence of distal femoral and proximal tibial epiph-

ysis in approximately 54 % of neonates at birth (femoral epiphysis appears by

34 weeks and tibial epiphysis by 39 weeks of intrauterine life).

3 Thyroid Disorders in Children