Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

DEMS Unit 4 > Congenital Hypothyroidism > Flashcards

Congenital Hypothyroidism Flashcards

1
Q

First endocrine gland to develop

A

thyroid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

from what do the follicular cells arise

A

endodermal pharynx– produce thyroxine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

embryonic lineage of parafollicular C cells

A

neural crest cells – produce calcitonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Embyology of thyroid gland

A

originates as proliferation of endodermal epithelial cells on median surface of pharyngeal floor between 1st and 2nd arches

  • initially hollow then solidifies and becomes bilobed
  • connected to tongue via thyroglossal duct as it begins initial descent
  • completes descent in 7th gestational week
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

when does thyroid complete its descent

A

7th gestational week

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

arrested migration of thyroid

A

when thyroid doesn’t make it all the way down to where it should be– leads to hypothyroidism– typically hypoplastic and won’t work
- can present as congenital hypothyroidism or make some then halt later in life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what happens in thyroid development after migration

A

at about 10-12 weeks, thyroid follicular cells undergo further differentiation – express genes that are essential for thyroid hormone synthesis
- gland begins to trap iodide and secrete thyroid hormones at 10-12 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

when does thyroid gland start making thyroid hormones

A

about 10-12 weeks gestation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how is iodide taken up

A

via sodium iodide symporter–oxidized to iodine on apical side of membrane then bound to tyrosyl residues in TG – forms MIT and DIT – coupling occurs and TG stored in colloid. When thyroid secretion needed (gets stimulated by TSH), TG taken up by endocytosis and digested by lysosomes to release T3, T4 into circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

ratio of secretion of T4:T3 by thyroid

A

10:1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

T3 vs rT3

A
  • T3= active; made by thyroid or converted from T4 via Type 1/II Deiodinase that takes off iodine from outer ring
  • rT3= inactive; made by deiodination of inner ring of T4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

where do you find the different deiodinases

A

Type 1- liver/kidney
Type 2- brain, sk muscle, pit, adipose
Type 3- placenta and brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

when is TSH first detected

A

12 weeks and increases from 18th week until birth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

when is H-P-T axis functional

A

midgestation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

HPT feedback control present at ? weeks

A

25 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

in what nuclei of hypothalamus is TRH produced

A

supraoptic and supraventricular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Does T3 or T4 feed back to hypothalamic and pituitary to control secretion

A

both can but mostly T3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

will fetuses with agenesis of thyroid have T4

A

yes; some maternal passes through placenta, so have T4 level of about 20% nl levels, and brain with type II deiodinase converts T4 to active T3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what protects hypothyroid babies from significant neuro sequellae

A

placental passage of maternal T4 and fetal brain rich in type II deiodinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what happen to thyroid hormones immediately after birth

A

TSH rises to 60-80 microunits/ml within 30 min of birth; this causes increased T3 and T4 to 1519 micrograms/dl by 24 hours
- comes down after several days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

congenital hypothyroidism

A

absent or decreased action of thyroid hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Prevalence of congenital hypothyroidism

A

1 in 4000; more common in Hispanic, less common in black

- Females:males = 2:1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how is congenital hypothyroidism detected

A

newborn screening in most industrialized countries– important since few to no sxs at birth and can cause permanent developmental delays when delaying treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

other conditions associated with congenital hypothroidism

A

congenital heart disease (may be as high as 5%)–usually ASD or PDA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Causes of dysgeneisis of thyroid
aplasia (no thyroid tissue), hypoplasia (poorly developed/small), ectopy (arrested migration)
26
2 main causes of congenital hypothyroidism
85% due to abnormal thyroid development (dysgenesis) - also can be problem with enzymes for thyroid hormone synthesis
27
PAX8
- transcription factor - important in initiation of thyroid cell differentiation, maintenance of differentiated state, and essential for thyroid cell proliferation - AD inheritance - variable phenotypes--severe hypoplasia associated with compensaged or overt hypothyroidism, ectopy, normal glands at birth - few cases associated w/renal agenesis (also in nephrogenic mesenchyme)
28
TITF2
transcription factor important in migration of thyroid precursor cells and transcriptional control of TG and TPO gene promoters in thyroid development - homozygous mutations result in Bamforth-Lazarus syndrome (CH, cleft palate, spiky hair, and variably bifid epiglottis and choanal atreasia)
29
TITF1
- homeobox domain transcription factor - important in development of gland and trasncriptional control of TG, TPO, and TSH receptor genes - also expressed in lung, forebrain, and pituitary gland - humans with heterozygous mutations associated with various combinations of CH, respiratory distress and neurological disorders
30
Bamforth-Lazarus
- associated with mutation in TITF2 transcription factor | - have congenital hypothyroidism (CH), cleft palate, spiky hair, and variably bifid epiglottis and choanal atresia
31
TSH receptor mutations
- TSH receptor gene encodes transmembrane receptor on surface of follicular cells; mediate effects of TSH and is critical for development/function of thyroid gland - can be heterozygous or homozygous - Heterozygous loss of funciton mutations- partial resistance with nl size gland and TSH elevation - Homozygous TSHR mutations usually cause CH with hypoplastic gland and decreased T4 synthesis
32
thyroid dyshormonogenesis
causes 15% of congenital hypothyroidism - generally autosomal recessive - goiter may be present - mutations in several genes coding proteins important in thyroid hormone synthesis
33
NIS
- sodium/iodide symporter - important for iodide transport from blood into thyroid cell (basal membrane) - mutations cause hypothyroidism of variable severity; goiter not always present (ppl with more iodide intake less likely to have severe hypothyroidism compared to those with iodide deficient diets)
34
rate-limiting step in thyroid hormone synthesis
iodide transport into cell via Na/I symporter
35
SCL26A4
encodes pendrin- important for efflux of iodide at apical membrane of thyroid follicular cells - mutations = Pendred's syndrome (associated with sensorineural congenital deafness adn goiter) - rarely present with CH; majority of individuals are euthyroid, at least under conditions of nl thyroid intake
36
TPO
- mutations here one of most common
37
TG
glycoprotein which is a key element
38
THOX1 and THOX2
?
39
Central hypothyroidism
hypothalamic or pituitary deficiency (TRH or TSH) - usually occurs in setting of multiple pituitary hormone deficiency (i.e. septo-optic dysplasia--affects pituitary, optic nerves, brain develops; developmental delays and blindness) - need to eval other pit hormones and obtain cranial MRI
40
Signs/sxs of congenital hypothyroidism
- not many so important to have newborn screen!! - large posterior fontanel - prolonged jaundice - macroglossia - hoarse cry - umbilical hernia - myotonia
41
Newborn screening
do at 3-5 days of age (not first day when elevated TSH--usually do last thing before babies go home) - 2 ways to do screening--- 1) Primary T4-- if T4 in lowest 10% of results on a given day, TSH will be measured. Abnormal if TSH >20 and will call PCP. If TSH
42
labs on primary congenital hypothyroidism
no/little T4/T3 -- lack of inhibition -- elevated TSH
43
why is thyroid hormone measurement complicated
- complicated due to binding to protein in blood - deficiencies and excess of thyroid binding proteins changes values of total thyroid hormones (deficient in TBG-- will have low total T4)
44
how much of T4 bound to TBG
75%
45
how much of T4 bound to TBPA
20%
46
how much T4 bound to albumin
4%
47
if you suspect issues with binding proteins what do you do
check free T4 and T3 uptake
48
T3 Uptake test
take pt sample and - used to look at binding proteins -add radiolabeled T3 tracer that will bind to available binding sites in pts serum -- add resin that will take up whatever T3 not bound to sites is taken up by resin. Result given by percent of initial radiolabeled T3 - nl is 25-35% taken up by resin -
49
T3 uptake test in hypothyroid
50
T3 uptake test in hyperthyroid
>35% - have more sites bound already in pts serum, so less binds and more available to be taken up by resin
51
If T3 uptake and T4 in same direction
thyroid disease | i.e. low uptake and low T4 --hypothyroid
52
If T3 uptake and T4 in opposite directions
TBG abnormality (i. e. high uptake and low T4 -- TBG deficient) - low TBG means less sites available for T3 to bind, so more will be taken up by resin
53
T3 uptake result in pregnancy
more TBG, so more binding sites for radioactive tracer to bind, meaning less can be bound by resin
54
why nl TSH but high total T4 common in adolescent girls
Estrogen and OCP--
55
what would you do if newborn screening showed low T4 and high TSH?
- confirmatory labs; if the same --primary hypothyroidism-- start baby on thyroid
56
what would you do if low T4 and low TSH?
- confirmatory labs with uptake and free T4
57
if low T4/TSH and nl FT4 with higher T3 uptake
TBG deficiency
58
what should neonatal T4 be on screening?
8-9
59
low T4, low TSH with low FT4 and lower T3 uptake
central hypothyroidism
60
Treatment for hypothyroidism
levothyroxine as early as possible - have to crush up--suspension not reliable - monitor levels every 3 months first 3 years in addition to 4 weeks after dose change
61
Pendred's syndrome
due to mutation in SCL26A4 -- - Autosomal recessive disorder associated with sensorineural congenital deafness and goiter - - rarely present with CH; majority are euthyroid, at least when adequate iodide intake

DEMS Unit 4 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions