Endo: Congenital Hypothyroidism

Question 1

What is the embryologic origin of thyroid follicular cells and C-cells?

Answer 1

• Follicular cells = endoderm (primitive gut tube)
• C-cells = neural crest

Question 2

A persistent thyroglossal duct will connect what two structures?

Answer 2

Thyroid and tongue (foramen cecum)

Question 3

Compare the amount of T3 v T4 produced by the thyroid

Answer 3

Thyroid produces much more T4 than T3

Question 4

What enzyme converts T4 into T3?

Where does this occur?

Answer 4

(Type 1/2) 5’ dieiodinase converts T4 into T3 in the periphery

Question 5

Describe thyroid hormone levels immediately after birth (2)

Answer 5

• There is a large surge in TSH right at birth
• There is a T4 surge a few weeks later

Question 6

If a fetus is unable to make any thyroid hormones, it will still have some thyroid hormones in utero. How does this occur?

Answer 6

1. Some T4 is able to cross placenta
2. Fetal brain has lots of type II deiodinase (converts T4 into T3)

Question 7

Why is congenital hypothyroidism on the newborn screen?

Answer 7

Untreated hypothyroidism causes irreversible damage to brain development and growth

Question 8

Define congenital hypothyroidism

What is the most common cause in USA?

Answer 8

• Congenital hypothyroidism = No thyroid hormones since birth
• Most common cause = thyroid dysgenesis (gland doesn’t develop properly)

Question 9

Name 3 transcription factor genes that have been linked to thyroid dysgenesis.

Answer 9

• PAX8
• TTF1/2

Question 10

What is thyroid dyshormonogenesis?

Name 1 physical exam finding

Answer 10

• Autosomal recessive defect in any of the enzymes required for thyroid hormone synthesis
• May have goiter (enlarged thyroid b/c high TSH increases the size of the gland cells, which themselves are functional)

Question 11

If a mother has Hashimoto’s thyroiditis, how will the baby be affected?

Answer 11

Fetus may have a transient hypothyroidism due to transfer of maternal antibodies

Question 12

Is central hypothyroidism typically an isolated finding or part of a larger problem?

Answer 12

Central hypothyroidism is usually associated with deficiencies in other hormones (hypopituitarism)

Question 13

When do symptoms begin to appear for congenital hypothyroidism?

Answer 13

Babies appear normal for first few weeks, and then symptoms appear

*This is why it’s on the NBS - catching it in asymptomatic phase prevents damage

Question 14

Name 6 signs/symptoms of congenital hypothyroidism

Answer 14

• Large posterior fontanel
• Prolonged jaunduce
• Protruding tongue, umbilicus, belly
• Poor brain development
• Poor muscle tone
• Puffy face

Question 15

TRH, TSH, and L4 levels in primary congenital hypothyroidism?

Answer 15

• High TRH, high TSH
• Low T4

*Thyroid can’t produce hormones, but hypothalamus and pituitary will keep trying to stimulate it

Question 16

When is the NBS performed?

What hormone is checked for hypothyroidism on the NBS?

Answer 16

Perform NBS after 3-5 days (after TSH surge)

Check T4 or TSH (depending on state)

Question 17

How is levothyroxine administered to babies? (route)

Answer 17

Tablets are crushed, made into solution, and then squirted into baby’s mouth

(NOT a suspension)

Question 18

Which form of NBS may miss central hypothyroidism?

Answer 18

Checking TSH only will miss central hypothyroidism