Wk1: Test1: 3 Thyroid Hormones: Synthesis, Actions, Regulation - Pierre

Question 1

the thyroid gland is composed of

Answer 1

follicles

Question 2

follicles are lined with — and filled with —

Answer 2

follicular cells

colloid

Question 3

the colloid is primarily composed of

Answer 3

thyroglobulin (Tg)

Question 4

thyroglobulin is synthesized by

Answer 4

follicular cells

Question 5

— is taken up by follicular cells and combined with Tg (Thyroglobulin) to form — and —

Answer 5

Iodide

Thyroxine T4

Triiodothyronine T3

Question 6

Follicular cells are also called — and are —

Answer 6

thyroid epithelial cells

polarized

Question 7

What does polarized mean

Answer 7

the basolateral membrane is connected to the blood stream and the apical side is exposed to the colloid

Question 8

Bidirectional Synthesis

Answer 8

iodide is taken up from the basolateral side, combined with Tg in colloid, T3 and T4 released on basolateral side

Question 9

Step 1: Iodide uptake by — on the basolateral membrane. It is powered by the — ion pump

Answer 9

Sodium/ Iodide Symporter (NIS)

Na/K ATPase (NKA) Ion Pump

Question 10

Mutation of the NIS gene is a rare cause of

Answer 10

congenital hypothyroidism

Question 11

low iodide levels — the amount of NIS and stimulate —

Answer 11

increase

uptake of iodide

Question 12

Low iodide levels — NIS expression and uptake

Answer 12

decrease

Question 13

Step 2: along the apical membrane I- is transported into the lumen by a

Answer 13

anion exchanger - Pendrin

Question 14

Mutation in pendrin gene causes —

Answer 14

Pendred Syndrome

Question 15

Pendred Syndrome is characterized by

Answer 15

defective organification of iodine, goiter, and sensorineural deafness

Question 16

Step 3: the enzyme — located at the apical border of the follicle cells catalyzes the oxidation of iodide to iodine

Answer 16

thyroperoxidase (TPO)

Question 17

Step 4: — is synthesized and released into the lumen via exocytosis

Answer 17

Thyroglobulin (Tg)

Question 18

Step 5: Tg is extruded into the lumen. 20% of its tyrosine residue is —. The catalyst of this reaction is —

Answer 18

iodinated

TPO

Question 19

Step 5: The initial product of tyrosine iodination are — and —

Answer 19

monoiodotyrosine (MIT)

diiodotyrosine (DIT)

Question 20

2 DITs coupled

Answer 20

T4 - Tetraiodothyronine

Question 21

1 DIT and 1 MIT coupled

Answer 21

T3 - Triiothryonine

Question 22

when iodine is abundant – is formed

when iodine is scarce — is formed

Answer 22

T4

T3

Question 23

there is enough thyroid hormones stored as iodinated thyroglobulin in the colloid to last the body —

Answer 23

2-3 months

Question 24

Step 6: When thyroid hormone is needed, — is “pinched” from the follicle

Answer 24

thyroglobulin

Question 25

Step 7: Intracellular proteases cleave off --- and ---, MIT and DIT from ---

Answer 25

T3, T4, Tg

Question 26

Step 8: --- and --- are secreted and MIT and DIT are ---

Answer 26

T3, T4 Recycled

Question 27

Iodine deficiency is assessed by measuring ---

Answer 27

iodide excreted >10ug/dL

Question 28

Iodine deficiency is most severe in

Answer 28

pregnant women and their babies

Question 29

T3 or T4 has higher binding affinity for proteins

Answer 29

T4

Question 30

T4 half life T3 half life

Answer 30

T4: 6-7 Days T3: 1-2 Days

Question 31

most circulating thyroid hormone is --- | there is 50x more than the other

Answer 31

T4

Question 32

the amount of circulation T3/T4 is -- times the amount secreted by the thyroid each day

Answer 32

3x

Question 33

99% of T3/T4 is bound to

Answer 33

plasma binding protiens

Question 34

What 3 proteins bind T3 and T4

Answer 34

TBG Albumin Transthyretin TTR

Question 35

TBG binding affinity

Answer 35

80% T4>T3

Question 36

Albumin binding affinity

Answer 36

up to 10% of T4 and 30% T3

Question 37

TTR binding affinity

Answer 37

10% of T4 Little T3

Question 38

T3 or T4 binds their receptor with more affinity

Answer 38

T3

Question 39

T3 or T4 the more active thyroid hormone

Answer 39

T3

Question 40

Many target tissues can regulate the conversion | of T4 to

Answer 40

either T3 or reverse T3

Question 41

rT3 is not

Answer 41

biologically active

Question 42

Most of the circulating T3 is derived from the peripheral conversion of --- into T3 and its release again into the circulation

Answer 42

T4

Question 43

Abnormal rate of conversion of T4 to rT3 is observed in

Answer 43

Euthyroid sick syndrome (ESS)

Question 44

T4 conversion to T3 via

Answer 44

5' monodeiodinase Activation

Question 45

T4 conversion to reverse T3

Answer 45

5 monodeiodinase Degredation

Question 46

Thyroid hormone synthesis and secretion are | maintained within narrow limits because of a

Answer 46

very sensitive | negative feedback

Question 47

A 50% decrease in plasma T4 | causes a --- times increase in plasma TSH.

Answer 47

50-100

Question 48

--- provides constant and necessary stimulus | for TSH secretion

Answer 48

TRH

Question 49

In the absence of TRH, the | secretion of TSH (and T4) does what

Answer 49

decreases to very low | levels

Question 50

The target tissue for TSH is the

Answer 50

thyroid where it increases the secretion of T4/T3.

Question 51

Negative feedback of thyroid hormones is exerted | mainly at the level of the

Answer 51

anterior pituitary gland

Question 52

Primary hyperthyroidism

Answer 52

low TSH

Question 53

Primary Hypothyroidism

Answer 53

High TSH

Question 54

Circulating T3/T4 enter cells by --- and | specific transporters such the ---

Answer 54

passive diffusion monocarboxylase 8 transporter (MCT8)

Question 55

Mutations in the MCT8 gene have been linked to what thyroid function abnormalities

Answer 55

low T4, high T3, high TSH

Question 56

After entering cells, T3 and T4 act primarily through nuclear receptors: the

Answer 56

thyroid hormone receptors (TRs).

Question 57

TRs bind to specific DNA sequences:

Answer 57

thyroid response elements (TREs) in the promoter region of target genes.

Question 58

TRs bind as homodimers or heterodimers with -- receptors

Answer 58

retinoic | acid X receptors (RXR)

Question 59

activated TR can --- the transcription of the target gene, depending on the nature of the regulatory elements.

Answer 59

stimulate or repress

Question 60

Mutations in TR can lead to ---, suspected when unbound thyroid hormone levels are increased without suppression of TSH.

Answer 60

thyroid hormone resistance (THR)

Question 61

Widespread Physiological Effects of Thyroid Hormone

Answer 61

see chart - slides 16 and 17

Question 62

Hyperthyroidism

Answer 62

over activity of thyroid leading to excess T4

Question 63

Hyperthyroidism is more common in men or women

Answer 63

women 5:1

Question 64

--- is most common cause of hyperthyroidism

Answer 64

Grave's Disease

Question 65

Euthyroidism

Answer 65

thyroid gland is functioning normally

Question 66

In --- , thyroid test results can be abnormal even though | the thyroid gland is functioning normally (abnormal T3/rT3 ratio)

Answer 66

euthyroid sick syndrome (ESS)

Question 67

ESS occurs in people who

Answer 67

have a severe illness other than thyroid disease.

Question 68

Hypothyroidism

Answer 68

Underproduction of thyroid hormones. One of the most common thyroid disorders.

Question 69

Hypothyroidism more common in men or women

Answer 69

women 5 - 8 x

Question 70

--- is the most common cause of hypothyroidism worldwide

Answer 70

iodine deficiency

Question 71

--- is the most common cause of hypothyroidism in iodine sufficient areas

Answer 71

Hashimoto’s thyroiditis

Question 72

Effects of thyroid hormone on energy at cellular level

Answer 72

Question 73

Effects of thyroid hormone on energy at body level

Answer 73