COngenital

Question 1

The thyroid is derived from what 2 embryonic lineages? What do they produce?

Answer 1

1. follicular cells (endodermal pharynx)
   - thyroxine
2. parafollicular C cells (neural crest)
   - calcitonin

*thyroid is the first endocrine gland to develop

Question 2

At what week does thyroid follicular cells undergo further differentiation essential for TH synthesis

Answer 2

10-12 weeks
- thyroid gland can now trap iodide and secrete TH

*HPT feedback is evident by 25 weeks

Question 3

Thyroid completes its descent in what gestational week?

Answer 3

7th week

Question 4

What enzyme(s) convert T4 → T3?

Answer 4

Type I + II deiodinase

*type III converts T4 into inactive rT3

Question 5

What happens to TSH levels immediately after birth?

Answer 5

w/in 30 min, TSH rises to 60-80 ul/ml → increases T4 +T3 to 15-19ug/dl by 24 hours.
- Spike!

*nl T4 4.5 to 11.2 mcg/dL

Question 6

Who is most likely to get congenital hypothyroidism?

Answer 6

Female 2:1
Hispanic

*there is an associated congenital HD

Question 7

How is Pax8 gene imp for thyroid development?

Answer 7

1. Initiation of thyroid cell differentiation
2. Maintenance of differentiated state
3. Thyroid proliferation

Pax8 mutation:
mild → severe hypothyroidism

Question 8

T3 functions

Answer 8

4 B's
Brain maturation
Bone growth
B-adrenergic effects
Basal metabolic rate ↑

Question 9

Txn factors imp in thyroid development

Answer 9

Pax8
TITF2
TITF1

*Mutationin these txn factors → congenital hypothyroidism

Question 10

TITF2

Answer 10

1. Migration of thyroid precursor cells
2. Txnal control of TG and thyroid peroxidase gene promoters

Mutation:
Congenital hypothyroidism (CH), cleft palate, spikey hair, bifid epiglottis
*slide with suprised faced kid

Question 11

TITF1

Answer 11

1. development of the gland
2. txnscriptional control of TG, TPO, and TSH receptor genes

mutation:
congenital hypothyroidism (CH), respiratory distress, neuro disorders

Question 12

Congenital Hypothyroidism

2 causes

Answer 12

1. 85% due to abnl Thyroid gland devel.

2. 15% due to thyroid dyshormonogenesis

Question 13

RLS of TH synthesis

Answer 13

NIS sodium/iodide symporter

- iodide transport from blood into thyroid cell (basal membrane)

Question 14

Central hypothyroidism

Answer 14

Central think brain

• Hypothalamic or pit deficiency
• MRI
• setting of mult pit hormone deficiency

Question 15

signs/sx of congenital hypothyroidism

Answer 15

1. baby usually appears nl
2. large posterior fontanel
3. prolonged jaundice
4. macroglossia
5. hoarse cry
6. umbilical hernia
7. hypotonia

• can get low IQ with late dx

Question 16

Ideal time to do newborn screening of total T4

Answer 16

3-5 days of age

1. Primary T4 - if T4 is in lowest 10% of results → measure TSH
   - if TSH >20 = abnl

• purpose of screening is to pick up primary Hypothyroidism, not central hypothyroidism

Question 17

Dx primary hypothyroidism in newborns (lab values)

Answer 17

*Measure TSH confirmatory labs if newborn had T4 in lowest 10% of results on given day

TSH abnl will be >50 and
T4

Question 18

Which is due to hypothyroid, and which due to TBG deficiency?
T3 uptake and T4 are in same direction (↓ low):
T3 uptake and T4 are in opp direction (↑T3 uptake, ↓T4)

Answer 18

T3 uptake by resin is low and T4 levels are ↓ low:
HYPOTHYROIDISM

T3 uptake and T4 are in opp direction (↑T3 uptake by resin, ↓T4):
TBG deficient

Question 19

NL TSH, high T4 in adolescent girls

Answer 19

birth control due to estrogen causing elevated TBG

nothing needs to be done

Question 20

What do you do?
T4 3.2 (nl = 8)
TSH>200 (nl=0.5-8)

What do they have?

Answer 20

do confirmatory labs

• T4 = 3.0
• TSH = 489

dx is primary hypothyroidism - start baby on thyroid meds

Question 21

What do they have?
TSH 4.6 (nl 0.5-8)
T4 3.2 (nl = 8)
FT4 1.8 (nl 0.8-2)
T3 uptake 35% (nl 25-35%)

Answer 21

Do confirmatory labs (can be TBG deficiency, or central hypothyroidism)
TSH 4.6 (nl 0.5-8)
T4 3.2 (nl = 8)
FT4 1.8 (nl 0.8-2)
T3 uptake 35% (nl 25-35%)

TBG deficiency - nothing to do - look at Free T4

Question 22

What do they have?
TSH 4.8  (nl 0.5-8)
T4 5.9  (nl = 8)
FT4 0.7 (nl 0.8-2)
T3 uptake 26% (nl 25-35%)

Answer 22

Central hypothyroidism

start with levothyroxine as early as possible