COngenital Flashcards
The thyroid is derived from what 2 embryonic lineages? What do they produce?
- follicular cells (endodermal pharynx)
- thyroxine - parafollicular C cells (neural crest)
- calcitonin
*thyroid is the first endocrine gland to develop
At what week does thyroid follicular cells undergo further differentiation essential for TH synthesis
10-12 weeks
- thyroid gland can now trap iodide and secrete TH
*HPT feedback is evident by 25 weeks
Thyroid completes its descent in what gestational week?
7th week
What enzyme(s) convert T4 → T3?
Type I + II deiodinase
*type III converts T4 into inactive rT3
What happens to TSH levels immediately after birth?
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
Who is most likely to get congenital hypothyroidism?
Female 2:1
Hispanic
*there is an associated congenital HD
How is Pax8 gene imp for thyroid development?
- Initiation of thyroid cell differentiation
- Maintenance of differentiated state
- Thyroid proliferation
Pax8 mutation:
mild → severe hypothyroidism
T3 functions
4 B's Brain maturation Bone growth B-adrenergic effects Basal metabolic rate ↑
Txn factors imp in thyroid development
Pax8
TITF2
TITF1
*Mutationin these txn factors → congenital hypothyroidism
TITF2
- Migration of thyroid precursor cells
- Txnal control of TG and thyroid peroxidase gene promoters
Mutation:
Congenital hypothyroidism (CH), cleft palate, spikey hair, bifid epiglottis
*slide with suprised faced kid
TITF1
- development of the gland
- txnscriptional control of TG, TPO, and TSH receptor genes
mutation: congenital hypothyroidism (CH), respiratory distress, neuro disorders
Congenital Hypothyroidism
2 causes
- 85% due to abnl Thyroid gland devel.
2. 15% due to thyroid dyshormonogenesis
RLS of TH synthesis
NIS sodium/iodide symporter
- iodide transport from blood into thyroid cell (basal membrane)
Central hypothyroidism
Central think brain
- Hypothalamic or pit deficiency
- MRI
- setting of mult pit hormone deficiency
signs/sx of congenital hypothyroidism
- baby usually appears nl
- large posterior fontanel
- prolonged jaundice
- macroglossia
- hoarse cry
- umbilical hernia
- hypotonia
- can get low IQ with late dx
Ideal time to do newborn screening of total T4
3-5 days of age
- 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
Dx primary hypothyroidism in newborns (lab values)
*Measure TSH confirmatory labs if newborn had T4 in lowest 10% of results on given day
TSH abnl will be >50 and
T4
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)
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
NL TSH, high T4 in adolescent girls
birth control due to estrogen causing elevated TBG
nothing needs to be done
What do you do?
T4 3.2 (nl = 8)
TSH>200 (nl=0.5-8)
What do they have?
do confirmatory labs
- T4 = 3.0
- TSH = 489
dx is primary hypothyroidism - start baby on thyroid meds
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%)
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
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%)
Central hypothyroidism
start with levothyroxine as early as possible
