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Physiology Exam 2 Endocrine (Shelby) > Thyroid > Flashcards

Flashcards in Thyroid Deck (108)
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1
Q

What % of circulating T3 is bound to a protein? What % is free?

A
bound = 99.5%
free = 0.5%
2
Q

How does coupling of iodinated tyrosine residues to make T3 and T4 molecules happen while they are attached to thyroglobulin?

A

Coupling when the molecule forms a tertiary and quarternary structure

3
Q

Thyroid hormones can undergo conjugation in the _____

which increases their solubility and _____ excretion

A

liver

biliary

4
Q

Of the ~400ug of iodine that is taken in daily from the diet, how much is excreted, and how much is taken up by the thyroid from a plasma pool?

A

320ug is excreted

80 is taken up by the thyroid

5
Q

What effect does TSH have on the iodide channels anoctamin-1?

A

opening of anoctamin-1 iodide channels on the apical membrane facilitating the leak of iodide into the colloid

6
Q

What 4 things do T3 and T4 bind to in the plasma?

A

thyroxine-binding globulin (TBG)
albumin
transthyretin
lipoprotein

7
Q

The oxidation of iodide and also organification coupling of MIT and DIT are facilitated by the enzyme thyroid peroxidase. What is an inhibitor of Thyroid peroxidase?

A

Propylthiouracil

8
Q

Where is thyroglobulin (Tg) produced?

A

cytosol of the follicular cell

contained in a vesicle with TPO

9
Q

The uptake (trapping) of iodine from the blood stream into the thyroid cells first occurs by iodine entering the follicular cell through the __________ symporter on the __________ membrane

A

Na+-I- symporter on the basolateral membrane

2 Na+ and 1 I- flow through the symporter

10
Q

The follicular cell of the thyroid has a lumen filled with ______

A

colloid

11
Q

The Na+-iodide symporter on the basolateral membrane of the thyroid follicular cells is a ___________ in autoimmune disease

A

autoantigen

12
Q

Why does a goiter happen when there is LOW iodide due to diet-induced deficiency?

A

TSH goes unopposed due to no negative feedback (increased tropic hormone secretion)
TSH = uncontrolled growth of thyroid

13
Q

Deiodinase type 3 converts T3 into ____ by removing an iodine from the _____ position, making it (active/inactive)

A

T2
inner 5
inactive

14
Q

Hypothyroid and Hyperthyroid effect on:

perspiration

A
HYPO = decrease
HYPER = increase
15
Q

Which transporter that thyroid hormones use to enter the cell has a preference for T4?

A

Na+ independent organic anion transporting polypeptide (OATP)

16
Q

What is the “organification defect” in relation to the thyroid

does it lead to hyper or hypothyroidism

A

iodine cannot be incorporated into tyrosine

HYPOthyroidism

17
Q

What do minor levels of thyroglobulin (Tg) that leak into the plasma indicate?

What do high levels of thyroglobulin (Tg) that leak into the plasma indicate?

A

minor = normal

high = HYPERthyroidism

18
Q

At what time during gestation is the hypothalamus-pituitary-thyroid axis functional?

A

12 weeks

19
Q

After traveling through the blood stream and entering a cell, what is the first thing that happens to T4?

A

Deiodinated into T3 so that T4 and T3 levels are equal

20
Q

What is the difference in structure between T3 and rT3?

A
T3 = lacking a 5' outer ring (has a 5 inner)
rT3 = lacking a 5 inner ring (has a 5' outer) = INACTIVE
21
Q

What is the main NONGENOMIC effect of thyroid hormones (especially T3)

A

rapid effects on ion influxes esp. in cardiovascular system

Ca2+ ATPase at plasma membrane and SR
Na+/H+ antiporter in muscle
oxygen consumption

ION FLUXES ION FLUXES ION FLUXES

22
Q

What effects do thyroid hormones have on metabolism?

A

increase glucose absorption from gut
increases gluconeogenesis
increases lipolysis
increases protein synthesis and proteolysis (futile cycling)
net degradation of tissue protein (negative N balance)

23
Q

How much blood does the thyroid gland receive?

A

2% of total blood flow

HIGH VASCULARITY!

24
Q

Which is made more, T3 or T4?

A

T4

25
Q

After traveling through the blood stream and entering a cell, what do T3 and T4 bind to?

Which one has a higher affinity for binding?

A

thyroid hormone receptor

T3 (10 fold!) (T3 ~90% of occupancy of TR)

26
Q

Hypothyroid and Hyperthyroid effect on:

thermogenesis

A
HYPO = decrease
HYPER = increase
27
Q

Where does the iodine we need to make thyroid hormones come from?

Where does the tyrosine we need to make thyroid hormones come from?

A

iodine = diet only

tyrosine = endogenous

28
Q

What is the effect of thyroid hormones on the sympathetic nervous system?

A

increased synthesis of B adrenergic receptors in cardiac/skeletal muscles and adipocytes

29
Q

What is coupled to form T4?

A

DIT (diiodotyrosine) + DIT (diiodotyrosine)

30
Q

Hypothyroid and Hyperthyroid effect on:

protein synthesis

A
HYPO = decrease
HYPER = increase
31
Q

What is the key hormone in inhibiting the release of TRH from the hypothalamus

A

free T3

32
Q

When the _______ detects low levels of thyroid hormone in the blood, it is stimulated to release ______ which stimulates the release of _______ from the pituitary, which in turn stimulates the steps of thyroid hormone synthesis and release at the thyroid

A

hypothalamus
TRH
TSH

33
Q

Calorigenic effect of thyroid hormones occurs in all tissues except:

A

brain
gonads
spleen

34
Q

Can hypothyroidism at birth be reversed?

A

yes with treatment

35
Q

What are the 4 transporters that thyroid hormones use to enter the cell

A
  1. Na+ taurochlorate cotransporting peptide (NTCP)
  2. Na+ independent organic anion transporting polypeptide (OATP)
  3. L- and T- type amino acid transporters (LAT)
  4. Monocarboxylate transporters (MCT)
36
Q

Hypothyroid and Hyperthyroid effect on:

intestinal glucose absorption

A
HYPO = decrease
HYPER = increase
37
Q

In the cell, once T3 or T4 has bound to thyroid hormone receptor, what does the thyroid hormone receptor bind to?

A

nuclear DNA on the TRE in the promoter region of genes regulated by T3 and T4

38
Q

If the follicular cell if stimulated by TSH, how does T3/T4 stored in the colloid get to the blood stream for secretion?

A
  1. follicular cell engulfs (endocytosis) Tg molecule with T3 and T4 attached to it by MEGALIN
  2. lysosomes enter vesicle, proteases split T3/T4 from Tg
  3. T3/T4 diffuses out into the blood
39
Q

How many Iodide transport defect-causing mutations of NIS gene have been identified?

A

6

40
Q

Hypothyroid and Hyperthyroid effect on:

lipolysis

A
HYPO = decrease
HYPER = increase
41
Q

What is responsible for the deactivation of thyroid hormone? (T3 to T2)

A

deiondinases

42
Q

Which is more active, T3 or T4?

A

T3

T4 is a PROhormone- converted to T3 to be active

43
Q

Which transporter that thyroid hormones use to enter the cell has a preference for T3?

A

Monocarboxylate transporters (MCT)

44
Q

What critical role does the hypothalamus-pituitary-thyroid axis play during gestation?

A

myelination of CNS
neural sprouting
growth of the fetus

45
Q

When doing a radioactive iodine uptake test, normal conditions would be ____% uptake of iodine after 6 hours

A

15%

46
Q

What stimulates the release of TSH from the pituitary?

What inhibits the release of TSH from the pituitary?

A

TRH (thyrotropin-releasing hormone) bind to a receptor on the thyrotrophs

dopamine, somatostatin, peripheral T4 and T3

47
Q

What is thyroglobulin? (Tg)

A

glycoprotein that contains ~132 tyrosine molecules contained in a vesicle in the colloid

***what iodine attaches to in the colloid before becoming T3 and T4

48
Q

Hypothyroid and Hyperthyroid effect on:

sleep

A
HYPO = sleepiness, tiredness
HYPER = insomnia
49
Q

Hypothyroid and Hyperthyroid effect on:

lipogenesis

A
HYPO = decrease
HYPER = increase
50
Q

Hypothyroid and Hyperthyroid effect on:

catecholamine levels

A
HYPO = none
HYPER = increase B adrenoceptors = increased sensitivity to catecholamines but serum level does not change
51
Q

What do parafollicular cells of the thyroid do?

A

release calcitonin

calcium and phosphate regulation

52
Q

What % of thyroid hormones secreted are T4?
What % of thyroid hormones secreted are T3?
What % of thyroid hormones secreted are rT3?

A
T4 = ~90%
T3 = ~10 %
rT3 = less than 1%
53
Q

Once the tyrosine molecules of thyroglobulin (Tg) are iodinated, what is the next step?

A

coupling to form T3 and T4

54
Q

What is coupled to form T3?

A

MIT (monoiodotyrosine) + DIT (diiodotyrosine)

55
Q

What two physical findings are associated with Pendred Syndrome

A

Goiter in childhood
hearing loss

***variability in the expression of the phenotype exists

56
Q

Hypothyroid and Hyperthyroid effect on:

serum cholesterol

A
HYPO = increase
HYPER = decrease
57
Q

Thyroid hormones are synthesized in the colloid by _________

A

thyroglobulin

58
Q

Hypothyroid and Hyperthyroid effect on:

Glycogenolysis

A
HYPO = decrease
HYPER = increase
59
Q

What is a way we can MEASURE the activity of the thyroid gland?

A

radioactive iodine uptake test
tracer dose of 123-iodine and labeled iodine and uptake measured by gamma detection

measuring Na+-iodide symporter activity

60
Q

What is the role of the Na+-Iodide symporter in a lactating mammary gland?

A

concentrating iodide in milk to supply newborns with iodide for thyroid hormone synthesis

61
Q

Of the ~132 tyrosine molecules on a thyroglobulin (Tg), how many of them become iodinated?
How many will be coupled to become active thyroid hormones?

A

20%

5%

62
Q

What is the storage site for hormones in the thyroid?

A

colloid

63
Q

If you stopped iodine intake from the diet, for how long could your thyroid function normally based upon stores of iodine?

A

2 months

64
Q

Monoiodotyrosine (MIT) is formed when an iodine is attached to a tyrosine within thyroglobulin (Tg) by thyroid peroxidase on carbon # ____

A

3

65
Q

outer ring deiodination is done by deiodinase type:

A

1 and 2

66
Q

mutations in the ________ causes hypothyroidism

A

Na+-iodide symporter

…on the basolateral membrane of the thyroid follicular cells

67
Q

inner ring deiodination is done by deiodinase type:

A

3

68
Q

Hypothyroid and Hyperthyroid effect on:

muscle wasting

A
HYPO = none
HYPER = increase
69
Q

What is the total idodine content of the thyroid in the form of idothyronine (or thyronines)

A

7500ug

70
Q

What is the Wolff-Chaikoff effect?

A

Increased serum Iodide –> increased TSH —> increased organification of iodide —> increased T3 and T4

*increased concentration of iodide in the thyroid

decreases organification of iodide —> decreased T3 and T4

71
Q

What stimulates the steps of thyroid hormone synthesis and release at the thyroid

A

TSH

72
Q

How does T4 and T3 inhibit the release of TSH

A

down-regulating the TRH receptor on thyrotrophs

73
Q

Organification of iodide can be regulated independently of ____

A

TSH

74
Q

In a LOW iodide diet, the activity of the Na+-iodide symporter on the basolateral membrane of the thyroid follicular cells is (increased/decreased)?

What steps in to compensate for the low iodide?

What physical manifestation can appear?

A

increased!

kidneys compensate to reduce excretion

goiter

75
Q

What are surgical/pharmological options for HYPERthyroidism?

A
  1. remove gland
  2. radioactive I-131 to destroy gland
  3. B-adgrenergic antagonists
  4. Propylthiouracil
76
Q

Other than the follicular cells of the thyroid, where else can you find the Na+-Iodide symporter?

What is different about the NIS in these tissues versus the thyroid?

A

gastric mucosa
placenta
lactating mammary glands

NOT under TSH regulation

77
Q

What is responsible for converting T4 into T3 in the periphery?

A

deiodinase:

Thyroid peroxidase TPO

78
Q

What is the most common effect that thyroid hormones mediate

A

genomic effects

transcription regulation of target genes

79
Q

What increases or decreases the activity of the sodium-iodide symporter on the basolateral membrane of the thyroid follicular cells?

A

DIET!!!! or diseased state

80
Q

TSH stimulates the release of thyroid hormones form the thyroid, but it also stimulates gene transcription of what specific things in the process of thyroid hormone synthesis?

A
  1. Na+-Iodide symporter
  2. Thyroglobulin
  3. Thyroid peroxidase
  4. T3 and T4
81
Q

DIiodotyrosine (DIT) is formed when an iodine is attached to a tyrosine within thyroglobulin (Tg) by thyroid peroxidase on carbon # ____

A

5

There is already an iodine on carbon 3 (MIT)

82
Q

Deiodinases type 1 and 2 convert rT3 into ____ by removing an iodine from the _____ position, making it (active/inactive)

A

T2
outer 5’
inactive

83
Q

Once iodide is in the follicular cell through the Na+-iodide symporter on the basolateral membrane, how does it get through the cell to the apical membrane

A

carried by PENDRIN

84
Q

Where in the cell is iodide oxidized to iodine?

What oxidizes it?

A

apical luminal membrane
thyroid peroxidase (TPO)
peroxide is the oxidizing agent

85
Q

Daily intake of iodine is roughly:

A

~400 ug

86
Q

Once T3 and T4 have been cleaved from thyroglobulin (Tg) and secreted into the blood stream, how are the rest of the MIT and DIT handled in the follicular cell?

A

deiodinated by intrathyroidal deiodinase

free iodine recycled for de novo synthesis of T3 T4

87
Q

Hypothyroid and Hyperthyroid effect on:

body weight

A
HYPO = increase (weight gain)
HYPER = decrease (weight loss)
88
Q

Deiodinases type 1 and 2 convert T4 into ____ by removing an iodine from the _____ position, making it (active/inactive)

A

T3
outer 5’
active

89
Q

What % of circulating T4 is bound to a protein? What % is free?

A
bound = 99.98% 
free = 0.02%
90
Q

What is thyroid peroxidase?

A

The enzyme involved in the oxidation of iodide and its incorporation into tyrosine residue

91
Q

Mutations to which transporter that thyroid hormones use to enter the cell are associated with psychomotor retardation and thyroid hormone resistance?

A

Monocarboxylate transporters (MCT) (MCT8 gene)

92
Q

Where does the process of T4 and T3 synthesis occur?

A

within the cytosol of the follicular cell

AND

the colloid

*****synthesis is INTRAcellular and EXTRAcellular

93
Q

Pendrin is a secretes iodide into the follicular lumen of the thyroid cells, but where else in the body can pendrine be found? What is its role?

A

Innear ear

endocochlear potential and structural development

94
Q

What is thyroglobulin?

Where do you find it?

A

the glycoprotein that serves as a scaffold for tyrosine iodination as well as storage of the thyroid hormone

Colloid of the follicular cell of the thyroid

95
Q

What is the condition called when there is a deficiency oh the hypothalamus-pituitary-thyroid axis during gestation?

A

Cretinism

96
Q

What effects do thyroid hormones have on the cardiovascular system?

A

T3 increases cardiac output and ventilation
T3 is chronotropic and inotropic
T3 reduces vascular resistance

97
Q

Thyroid hormones act synergistically with GH and growth factors to promote ___________ in fetal development

A

bone formation

98
Q

Hypothyroid and Hyperthyroid effect on:

Basal metabolic rate

A
HYPO = decrease
HYPER = increase
99
Q

In Grave’s disease, what stimulates the release of T3 and T4 causing hyperthyroidism?

A

autoantibodies that IMITATE TSH

bind to the TSH receptor and stimulate thyroid

100
Q

What are the calorigenic actions of thyroid hormones?

A

increased oxygen consumption resulting in increased BMR and temperature

by increasing the activity of the Na-K-ATPase pump

101
Q

After iodide has entered the follicular cell, how does it get into the colloid?

A

iodide channel anoctamin-1 on the apical membrane

102
Q

Having low iodide in the diet can lead to hypothyroidism goiter for anyone, but for what group of people is this particularly overt

A

Those with Pendred syndrome

103
Q

Hypothyroid and Hyperthyroid effect on:

Proteolysis

A
HYPO = decrease
HYPER = increase
104
Q

Hypothyroid and Hyperthyroid effect on:

gluconeogenesis

A
HYPO = decrease
HYPER = increase
105
Q

Deiodinase type 3 converts T4 into ____ by removing an iodine from the _____ position, making it (active/inactive)

A

rT3
inner 5
inactive

106
Q

What helps endocytosis of thyroglobulin (Tg) with iodinated tyrosine residues back into the follicular cell from the colloid

A

megalin

107
Q

Iodide transport defect is a mutation in the ______ gene that causes:

A
NIS gene (Na+-Iodide-symporter) 
HYPOthyroidism, goiter, reduced uptake of radio-iodide
108
Q

In the _____, iodine attaches to a tyrosine on a thyroglobulin molecule contained in a vesicle with TPO

A

colloid