Endocrine - Thyroid Physiology Flashcards

1
Q

What are the classic hormone groups?

A

Amine hormones (Tyrosine derivatives)
Steroids
Peptides
Proteins

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2
Q

Do thyroid hormones behave like amine hormones?

Do thyroid hormones have rapid enzymatic synthesis?

A

No

Thyroid hormones are slow

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3
Q

Do thyroid hormones behave like amine hormones?

Are thyroid hormones stored in secretory granules?

A

No

Thyroid hormones are stored outside the cell that synthesized it

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4
Q

Do thyroid hormones behave like amine hormones?

Are thyroid hormones water soluble?

A

No

Iodides present prevent water solubility

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5
Q

Do thyroid hormones behave like amine hormones?

Do thyroid hormones have a long or short half-life?

A

Long

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6
Q

Do thyroid hormones behave like amine hormones?

Do thyroid hormones have a membrane receptor?

A

No

Thyroid Hormones hve intracellular receptors

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7
Q

Where are Thyroid hormones made?

A

In thyroid follicular cells

Sphereical epithelial cells

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8
Q

Define:

Colloid

What is it?

A

Stored thyroid hormones in the center of follicular cells

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9
Q

What are the three major steps of thyroid hormone synthesis?

A
  1. uptake and concentration of iodide (I-) in the gland
  2. Oxidation and incorporation of I- in tyrosine’s phenol ring
  3. Coupling of two iodinated tyrosines to form T4 or T3
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10
Q

Thyroglobulin is secreted and iodinated by…

A

Thyroid epithelial cells

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11
Q

What is the effect of low iodine in the body?

A

Decreases the rate of thyroid synthesis

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12
Q

What is the effect of high levels of iodine on the body?

A

Suppresses thyroid synthesis

Wolff-Chaikoff effect

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13
Q

What is the purpose of storing iodine in the body?

A

It protects the body from iodinen deficiency for an extended period of time

Stored I= within the gland is 100x greater than daily need (80 ug)

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14
Q

TH synthesis: Step 1

How is I- transported into the thyroid gland?

A

vs its electrochemical gradient by a 2Na+-I- symporter in the basement membrane of thyroid epithelial cells

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15
Q

TH synthesis: Step 1

____ block active transport of I-

A

ClO4-
SCN-

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16
Q

TH Synthesis: Step 2

Thyroglobulin

Define

A

Scaffold to make Thyroid Hormone

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17
Q

TH Synthesis: Step 2

Tyrosine Iodination

A

I- is oxidized and incorporated into tyrosine both by the enzyme thyroid peroxidase (TPO)

Oxidize I-l Iodinize Tyrosine

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18
Q

TH Synthesis: Step 2

The residues of thyroglobulin form…

A

MIT or DIT

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19
Q

TH Synthesis: Step 3

2 DIT molecules couple to form…

A

T4

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20
Q

TH Synthesis: Step 3

1 MIT and 1 DIT couple to form…

A

T3

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21
Q

What is the ratio of T4 to T3 synthesized by the thyroid gland?

A

10-20 T4 : 1 T3

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22
Q

How is thyroid hormone secreted?

A

Thyroglobulin enter thyroid follicular cell via endocytosis
Lysosomal proteases hydrolyze the thyroglobulin
T4 and T3 are released
MITs and DITs aew deiondinated and I- recycles

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23
Q

_ is the active form of Thyroid Hormone

A

T3

4X more potent than T4

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24
Q

____% of thyroid hormone secreted is T4

A

90%

T4 is a prohormone

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25
Q

____% of thyroid hormone secreted is T3

A

9%

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26
Q

____% of thyroid hormone secreted is rT3

A

1%

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27
Q

What happens to T4?

A

Peripheral conversion of T4 to T3 through the action of specific deiondinases

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28
Q

_ thyroid hormone increases with cold temperature?

A

T3

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29
Q

_ thyroid hormone increases during starvation

A

rT3

30
Q

What is the purpose of rT3?

A

To eat up energy to prevent T3 use

31
Q

5’MD is highly active and converts T4 into…

A

T3

32
Q

5MD is highly active and converts T4 into…

A

rT3

33
Q

What occurs when there is a decrease in T4 to T3 conversion?

A

Fasting
Malnutrition
Physicalo Trauma
Drugs
Systemic Illness
Old Age

34
Q

If starving and cold, which factor wins out?

A

Make more T3

35
Q

How do T3 and T4 circulate the blood?

A

70% bound to thyroxine-binding globulin (TBG) bindingh protein
29.5% bound to prealbumin and albumin
Low levels of free hormone

36
Q

What is the purpose of T4 and T3 as free hormones?

A

Binding proteins create a reservoir of hormone
protects from acute changes in thyroid gland function

37
Q

If free T4 decreases suddenly…

What happens to bound T4?

A

The constant release and rebinding to binding proteins can replace lost free T4

38
Q

What if the liver makes more binding protein?

This can happen during pregnancy

A

Alterations in RBG do not disturb biolgical function (if thyroid gland is normal)

39
Q

What determined hyper/hypo thyroidism?

A

The concentration of free hormone

40
Q

What is a major stimulator of thyroid hormone stimulation?

A

Thyroid - Stimulating Hormone (TSH)

TSH is under negative feedback control

41
Q

What is the function of TSH?

A

Stimulates almost every step in the pathway of TH synthesis
Stimulates growth (goiter) and vascularity (Bruit) of thyroid gland

42
Q

Feedback control of Thyroid Hormone is sensitive.

Explain

A

Changes in thyroidh ormone levels of only 10-30% are eno9ugh to change TSH in the opposite direction

43
Q

What is the relationship between T3 and TSH?

A

↑T3 ↓TSH

44
Q

What characteristic of T4 gives it a half life of 6 days?

A

T4 has a higher affinity for TBG

45
Q

Why is T3 the biologically active hormone?

A

T3 has a higher affinity for thyroid receptor

46
Q

When treating hypothyroidism, why do we give synthetic T4 (Levothyroxine) instead of synthetic T3 (Liothyronine)?

A

Levoythroxine - mimics true physiology, low cost, lacks allergens, easy lab measurements, long half-life (↑ compliance), more stable
Liothyronine - shorter half life (multiple doses/day), expensive, harder to monitor, higher activity (dangerous)

47
Q

What is the function of T3?

A

Brain maturation
Bone growth
β - adrenergic effects
BMR increases

4 B’s

48
Q

Actions of Thyroid Hormones

Pathway

A

T4 → 5’-iodinase →T3 →T3 binds nuclear receptor → DNA transcription → mRNA translation → synthesis of new proteins → 4B’a functions

49
Q

T3’s function in bone growth:

A

Growth formation
Bone maturation
T3 stimulates secretion of GH and remodeling of mineralized bone

TH accelerates shedding of skin and hair

50
Q

T3’s function in BMR:

A

↑Na-K ATPase
↑O2 Consumption
↑Heat production
↑# and size of mitochondria

Regulates BMR

51
Q

T3’s function in metabolism:

A

↑Glucose absorption
↑Glycogenolysis
↑Gluconeogenosis
↑Lipolysis
↑Protein synthesis and degredation

52
Q

T3’s function in cardiovascular:

A

↑CO

↑HR, SV, contractility, SBP, ↓DBP, vasodilation, ↓ SVR

53
Q

Define

Synpathomimetic

What is it? What does it do?

A

Many actions of high thyroid hormone levels resemble ↑ed SNS activity
reinforces CV resoponses to Epi and NE
Permissive effect for Epi and NE on lipolysis, glyconeolysis, and GNEO

54
Q

Symptoms of Hyperthryoidism:

A

Nervousness
Insomnia
Anxiety
Restlessness
Sweating
Heat intolerance
Tremor
Weight Loss
Palpitations
Tachycardia

55
Q

T3’s effect in CNS development:

A

T3 receptor is expressed in the brain throughout fetal life
Activity of 5’ deiodinase is augmented
Degredation of T3 is diminished

56
Q

TH enhances a variety of neurally controlled functions:

A

↑speed and amplitude of reflexes, wakefulness, alertness, responsiveness to various stimuli, awareness of hunger, memory and learning capacity
Normal emotional tone

57
Q

What happens to a fetus if a. mother has hypothyroidism and T3 is defificent in utero?

A

Impaired growth of the cerebal and cerebellar cortex
Imparied proliferation of axons and branching dendrites
Impaired myelinization
Irreversible brain damage if not treated immediately after birth
Biochemically: ↓RNA and protein content, protein synthesis, enzymes for DNA synthesis, NT receptors, NT synthesis

58
Q

Symptoms of Congenital Hypothyroidism:

A

Short stature
Malformed legs
Dull expression
Intellectual disabilities
delayed puberty
muscle weakness

59
Q

Define

Hypothyroidism

A

A deficiency of thyroid hormones

Under active thyroid

60
Q

Symptoms of Hypothyroidism

A

Fatigue, lethargy
Weight Gain
Cold intolerance (↓BMR)
Muscle aches, stiffness
Somnolence (drowsiness)
Thinning hair
Dry Skin
Prolonged reflex times
Depression
Mental Slowness
Constipation
Amenorrhea (heavy/irregular periods)
Puffy face (myxedema)
Goiter

Water retention

61
Q

Primary causes of hypothyroidism

A

Thyroid failure
Iodine insufficiency
↓T4&T3
↑TSH
Hashimoto’s Thyroiditis

Autoimmune, thyroid antibodies damage thyroid

Feedback works

62
Q

Secondary Causes of Hypothyroidism

A

Pituitary or hypothalamic failure
↓T4 &T3
↓TSH
Feedback wont work

No goiter, not a problem with thyroid

63
Q

Define:

Hyperthyroidism

A

Excess thyroid hormones

64
Q

Symptoms of Hyperthyroidism:

A

Heat intolerant (↑ BMR)
Weight loss
Palpitations
Nervousness, anxiety, irritability
Tremor
Moist, warm skin
↑defecation frequency
Goiter
Bruit over thyroid
Pretibial myxedema (Grave’s Disease)
Fatigure
Exopthalamos, lid retraction
Forward siaplacement of eyeballs

65
Q

Primary causes of Hyperthyroidism

A

Graves Disease
↑T4 and T3
↓TSH
Thyroid Stimulating Immunoglobulins (TSI)
Hypersecreting thyroid tumor (Toxic adenoma)

66
Q

Define

Graves Disease

A

Autoimmune disease in which antibodies target thyroid receptor activating thyroid hormone synthesis

Stimulate gland, Goiter

67
Q

Secondary Causes of Hyperthyroidism

A

Excess TSH or TRH
Feedback isnt working
↑T4&T3
↑TSH

68
Q

What happens if you have low TSH and T3/T4?

A

Tropic Hormone Deficiency
Secondary Hypothyroidism

69
Q

What happens if you have High TSH and Low T3/T4?

A

Primary failure of target endocrine organ
Primary Hypothyroidism

70
Q

What happens if you have High TSH and High T3/T4?

A

Seecondary hyperthyroidism
Autonomous secretion of tropic hormone
TSH-secreting tumor

No feedback

71
Q

What happens if you have Low TSH and High T3/T4?

A

Primary Hyperthyroidism
Autonomous secretion of target endocrine organ

Graves Disease; goiter