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Patient > Therapeutics of thyroid disease > Flashcards

Therapeutics of thyroid disease Flashcards

1
Q

what cells secrete T3 and T4

A

Thyroid follicular cells

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2
Q

where is the thyroid gland? what does it consist of?

A

in front of the trachea

2 lobes

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3
Q

TF: some people have a third lobe?

A

TRUE

10-30%

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4
Q

if someone has a third thyroid lobe what is it called?

A

pyramidal

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5
Q

what are the functional units of thyroid cells?

A

thyroid follicles which are filled with thyroglobulin

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6
Q

what is the point of thyroglobulin?

A

acts as a store of iodide

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7
Q

how long can thyroglobulin supply thyroid hormones for?

A

90 days

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8
Q

what are parafollicular C cells?

A

in between the follicles

for calcitonin production

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9
Q

what happens when the body gets cold- in relation to the thyroid

A

thyrotropin releasing hormone from the hypothalamus

this causes the anterior pituitary to release TSH
TSH goes to the thyroid gland and triggers T3 and T4 release

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10
Q

T__ does negative feedback. explain?

A

3
to the anterior pituitary to reduce the amount of TSH secreted
AND
longer loop feedback to reduce TRH secreted from the hypothalamus

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11
Q

explain how low T3 concentrations increase the thyroid gland

A

Low T3 concentrations- likely we also have low signal of TRH from hypothalamus
Pituitary Thyrotropes will then increase the amount of TSH which will then increase amount of thyroid hormone secreted
This causes the enlargement of thyroid cells to increase amount of thyroid hormones

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12
Q

explain how high T3 concentrations causes thyroid regression?

A

High T3- TRH from hypothalamus will be low, will cause Pituitary thyrotropes to reduce TSH production (a and b subunits= of the TSH protein)
The production of TSH hormone will be low
This reduces thyroid gland activity.
Decrease in size of the thyroid gland

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13
Q

the TSH receptors are located on?

A

thyroid follicular cells

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14
Q

the TSHR is a ______ receptor.

how does this work?

A

GPCR

which activates adenylate cyclase to produce the intracellular messenger cyclic AMP

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15
Q

cAMP activates what In the cell

A

all functional aspects of the cell

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16
Q

what 4 things does cAMP do to the thyroid cells

A
  1. Thyroglobulin synthesis- colloid in the center of each of these follicles
  2. Iodide pumping into the thyroid follicular cells and follicular lumen;
  3. Iodination by thyroid peroxidase;
  4. Endocytosis, proteolysis and hormone release
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17
Q

how is iodide from the diet transported into the follicular lumen?

A

from the blood
over the basolateral membrane into the follicle via Na/Iodide symporter which is in conjunction with the Na/K ATPase pump

then across the apical membrane into the lumen via Pendrin transporter for I and CL ions

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18
Q

what transporter brings iodide over the basolateral membrane from the blood stream?

A

Na/K pump in conjunction with Sodium/ iodide symporter (NIS)

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19
Q

What transporter transports Iodide over the apical membrane?

A

Pedrin for I and Cl ions

exchanger

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20
Q

how many Na ions and I- ions are bought across the basolateral membrane at one time?

A

2 Na for each 1 I-

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21
Q

what happens to the iodide once it enters the lumen?

A

oxidised to atomic iodine.

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22
Q

where is thyroglobulin produced? where does it end up?

A

thyroid follicular cells

released by exocytosis into the lumen

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23
Q

where is the thyroid peroxidase enzyme complex located?

A

spans the apical membrane

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24
Q

what does the thyroid peroxidase enzyme complex do?

A

it adds iodide onto tyrosine residues on the thyroglobulin backbone

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25
Q

how many places on the tyrosine residue can iodine be added onto?

A

2- either side of the OH

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26
Q

how is iodine bound to the tyrosine residues

A

covalently

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27
Q

what two things can be made when the iodine is bound to the tyrosine residues?

A

mono-iodotyrosine

Di-iodotyrosine

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28
Q

when is Di-i made?

A

when 2 iodine molecules are added to the backbone

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29
Q

what does the addition of either one or 2 iodines effect?

A

wether T3 or T4 is produced

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30
Q

what enzyme conjugates 2 tyrosines together?

A

Tyrosine peroxidase enzyme

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31
Q

TF: tyrosine peroxidase enzyme can conjugate more than 2 tyrosine molecules together

A

FALSE- always 2

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32
Q

how do you get T3?

A

if you conjugate a DIT with a MIT

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33
Q

How do you get T4?

A

if you conjugate DIT and DIT

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34
Q

what bond is formed when you conjugate 2 tyrosine molecules?

A

ester

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35
Q

where does iodation and conjugation via TPO occur?

A

in the thyroid follicular lumen

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36
Q

what happens to the iodinated thyroglobulin once its formed?

A

moves back into the cells by endocytosis

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37
Q

what happens to the conjugated iodinated tyrosine residues once they’re back in the cells

A

T3 and T4 is cleaved from thyroglobulin and released by the cells into the bloodstream

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38
Q

how are the conjugated, iodinated tyrosine residues cleaved from thyroglobulin

A

proteolysis by lysosomes

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39
Q

what happens to the thyroglobulin and iodide once this process is complete?

A

recycled

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40
Q

what is the major form of thyronine hormone in the blood?

A

T4- thyroxine

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41
Q

T4 has a _____ half life then T3?

A

LONGER

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42
Q

T4 is ______ potent than T3?

A

less

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43
Q

TF: T4 can be converted into T3?

A

true

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44
Q

is reverse T3 secreted alot?

A

no less than 1%

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45
Q

what is reverse T3?

A

MIT is reversed

46
Q

if levels of T4 are too high, what will the body do?

A

convert it to rT3

47
Q

Levothyroxine sodium treats?

A

hypothyroidism

48
Q

liothyronine sodium treats?

A

hypothyroidism

49
Q

what does levothyroxine sodium contain?

A

thyroxine T4

50
Q

what does liothyronine sodium contain?

A

T3

51
Q

drug treatments for hyperthyroidism? mechanism of action?

A

block synthesis of thyronine hormones
Carbimazole tablets
propylthiouracil tablets

52
Q

T4 is hydro____. therefore ______ in serum

A

phobic

insoluble

53
Q

why can liver disease lead to loss of effective T4 transport?

A

as the liver makes the binding proteins needed to transport hydrophobic T4 in the blood

54
Q

what is the most important thyroid hormone binding protein?

A

TBG- thyroxine- binding globulin

55
Q

what binding protein delivers most thyroid hormones to the brain?

A

transthyretin (TTR)

56
Q

transthyretin binds ___% of T4

A

20

57
Q

Thyroxine binding globulin binds ___% T4. AND prevents its loss in…

A

70-75

urine

58
Q

TF: transthyretin binds T3 and T4

A

false only T4

59
Q

What is the ratio of :

protein bound T4:T3

A

20:1

60
Q

albumin binds __% T3 and ___% T4

A

30

10

61
Q

examples of transporters which allows T3 and T4 to enter cells?

A

OATP1c1
MCT8
MCT10

62
Q

T_ is biologically active

A

3

63
Q

what must happen to T4?

A

be converted to T3

64
Q

what converts T4 into T3?

A

INTRACELLULAR iodothronine deiodinases- iodine removed

65
Q

where are iodothronine deiodinases (DIOs) located

A

intracellularly

66
Q

what does the enzyme iodothronine deiodinases (DIOs) contain?

A

seleno-cysteine

67
Q

how does the selene-cysteine in the iodothronine deiodinases convert T4 into T3?

A

selenium accepts iodide

68
Q

how many types of DOI’s are there?

A

3

69
Q

which types of DIOs make T3?

A

DIO1 or DIO2

70
Q

which types of DIOs make rT3?

A

DIO1 and DIO3

71
Q

What is DIO1 important for?

A

circulating t3

72
Q

Where does DIO1 predominate?

A 
the liver
kidney 
muscle 
all good blood supply!
thyroid
73
Q

DIO1 produces most of the _____ T3. NOT _____ T3.

A

INTRACELLULAR

circulating

74
Q

DIO2 is important for?

A

converting intracellular T4 into T3

75
Q

Where does DIO2 predominate?

A

CNS
pituitary thyrotropes
skeletal muscles sometimes

76
Q

DIO2 controles?

A

intracellular T3 levels

77
Q

what is DIO2 important for?

A

feedback regulation

78
Q

what does DIO3 produce?

A

rT3

79
Q

why is DIO3 important?

A

prevents thyroid hormone reaching specific tissues e.g. pregnancy

80
Q

what happens to DIO3 when you produce too much thyroid hormone?

A

it increases to protect from thyroid overload

81
Q

thyroid hormone receptors are _____ receptors

A

nuclear
TRa
TRb

82
Q

how do thyroid hormone receptors exist?

A

as heterodimer with retinoid X receptors (RXR)

transcription factors

83
Q

how do thyroid hormone receptors in the nucleus work when thyroid hormone isn’t present?

A

bind to Thyroid response element (TRE) of the gene
if thyroid hormone ISNT present, it blocks transcription by recruiting repressors and preventing transcription for that gene?

84
Q

what happens when thyroid hormone binds to receptors in the nucleus?

A

the repressors will leave and the gene will be transcribed and a protein will be produced

85
Q

TR have a ____ fold affinity for T3 than T4

A

15

86
Q

TF: thyroid hormone binding ONLY increases transcription.

A

FALSE

can inhibit- depends on the cell type

87
Q

what regulates intracellular supplies of T3 to the nucleus of T3 target cells?

A 
MCT8 
MCT 10 
OATP1C1 
DIO2, 3
T4
rT3
88
Q

In the anterior pituitary gland T3 binding has a _____ effect on transcription

A

promoting

89
Q

what happens in the anterior pituitary when T3 binds?

A

increase in growth hormone produced

90
Q

T3 ____ prolactin production

A

decreases

91
Q

T3 ______ alpha and beta subunits of TSH

A

decreases

92
Q

why does T3 reduce the amount of prolactin and alpha and beta subunits of TSH?

A

as if there’s a high amount of T3, you dont need any more

so by decreasing these, no more T3 will be produced

93
Q

TF: T4 conversion to T3 only happens intracellularly

A

FALSE

intra or extra

94
Q

biological actions of thyroid hormones?

A 
metabolic rate control 
growth 
foetal development 
CV effects 
muscoskeletal effects
95
Q

how does T3 control basal metabolic rate?

A

In this case the T3 increases transcription: you will increase the NA/K ATPase pump proteins, mitochondrial resp enzymes, other enzymes and proteins for tissue growth and maturation
If you increase the MRE then you will have a higher oxygen consumption, so effects the heart to pump more blood, also effects ventilation to increase delivery of oxygen
Increased ventilation also needed to rid body of CO2
Increased metabolic rate: Muscle mass and adipose will decrease as need the nutrients released from their breakdown
Increased body temperature- other mechanisms needed to bring this down

96
Q

what can deficiencies in thyroid hormones lead to?

A

abnormal growth, development, reproduction, behaviour and metabolism

effects all organs throughout life

97
Q

role of thyroid hormone in foetal development?

A

developing neural and skeletal systems

98
Q

loss of T4 supply to a foetus leads to irreversible….

A

mental impairment and dwarfism

99
Q

what is this lack of T4 supply to a foetus known as?

A

congenital iodine deficiency syndrome- mental impairment and dwarfism

100
Q

if thyodide hormones are disrupted in the foetus what can happen?

A

stillbirths
miscarriage
congenital morbidity and mortality
congenital iodine deficiency syndrome

101
Q

if thyroid hormones are disrupted in a neonate what can occur?

A

neonatal goiter
neonatal hypothyroidism
impaired mental function

102
Q

if thyroid hormones are disrupted in childhood and adolescent?

A

loiter- swelling round the neck
hypothyroidism
impaired mental function
impaired physical function

103
Q

metamorphosis requires….

A

thyroid hormones

in other species obviously

104
Q

overall cardiovascular effects of T3?

A 
increases: 
cardiac contraction and output 
heart rate 
oxygen supply to tissues 
CO2 removal from tissues
105
Q

physiological effects on cardiovascular function of T3?

A

increased:
myocardial Ca2+ uptake
expression of a-myosin heavy chain and DECREASED expression of b
expression of Ryan-dine receptor in SR

106
Q

T3 causes vaso____

A

dilation

bring body temperature down

107
Q

T3 _____ sensitivity to catecholamines?

A

INCREASES

108
Q

T3 bone turnover effects?

A

stimulatory effect increasing formation and resorption

109
Q

T3 effect on linear bone growth?

A

increases after birth

110
Q

T3 _____ rate of muscle relaxation?

A

INCREASES

111
Q

muscoskeletal effects when you have hypo or hyperthyroidism?

A

muscle tremors and weakness

Patient (19 decks)

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