Congenital Hypothyroidism

Question 1

Arises from 2 distinct embryonic lineages:

Answer 1

• follicular cells (endodermal pharynx)

- parafollicular C-cells (neural crest)

Question 2

T or F: Placenta allows passage of small quantities of maternal T4

Answer 2

True: in athyrotic neonates, cord blood T4 level is about 20% normal

Question 3

Fetal brain rich in what type deiodinase

Answer 3

type II deiodinase

Question 4

Causes of congenital hypothyroidism

Answer 4

• 15% inborn error of thyroid hormonogenesis ( autosomal recessive pattern)
• 85% abnormal thyroid gland development (dysgenesis)

Question 5

T of F: Accumulating evidence that genetic factors are involved in pathogenesis

Answer 5

yes, genes involved in thyroid structural development are:

• PAX8
• TITF2
• TITF1
• TSHR

Question 6

Genes involved in inborn error of thyroid hormonogenesis (thyroid dyshormonogensis)

Answer 6

• NIS:
• SCL26A4
• TG
• TPO
• THOX1 & 2

Question 7

Briefly describe fxn of genes in thyroid dyshormonogenesis

Answer 7

• NIS: Na+/I- transporter
• SCL26A4: iodide transporter apical
• TG: thyroglobulin
• TPO: thyroid peroxidase
• THOX1 & 2: enzyme oxidases

Question 8

Briefly describe fxn of genes in thyroid dygensis

Answer 8

• PAX8: differentiaion and proliferation
• TITF2: migration & transcription control
• TITF1:transcription factor
• TSHR: receptor

Question 9

Central hypothyroidism

Answer 9

• Hypothalamic or pituitary deficiency
• Usually occurs in setting of multiple pituitary hormone deficiency - i.e., septo-optic dysplasia
• Need to evaluate other pituitary hormones and obtain cranial MRI

Question 10

Signs/Symptoms of Congenital Hypothyroidism

Answer 10

Almost always overlooked
Baby usually appears entirely normal!
Large posterior fontanel
Prolonged jaundice
Macroglossia
Hoarse cry
Umbilical hernia
Hypotonia

Question 11

Newborn Screening

Answer 11

Best to do at 3-5 days of age
Two different screening methods:

1. Primary T4 – If T4 is in the lowest 10% of results on a given day, TSH will be measured
   - abnormal if TSH > 20 U/ml and call PCP
   - If TSH< 20, will not call but could still be abnormal (ie central hypothyroidism)
2. Primary TSH – this will miss central hypothyroidism

If abnormal screen, draw confirmatory labs

Question 12

Tx of CH

Answer 12

• Start treatment with levothyroxine as early as possible!!

- Levels monitored every 3 months in the first 3 years of life in addition to 4 weeks after dose change

Question 13

T3 uptake interpretation

Answer 13

• Low T3 uptake and Low T4 – Hypothyroid (same “direction”) THYROID DISEASE
• High uptake and Low T4 – TBG deficient (opposite “direction”) TBG ABNORMALITY

Question 14

TSH fluctuation after birth

Answer 14

• Within 30 minutes after birth, TSH rises to levels of 60-80 uU/ml
• TSH rise results in increases in T4 and T3 to 15-19 g/dl by 24 hours