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FHB Hormone/Repro > 77 - Thyroid > Flashcards

77 - Thyroid Flashcards

1
Q

What is the thyroid gland anterior to?

A

Cricoid cartilage

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2
Q

What aa. supply the thyroid gland?

A
  • Superior thyroid a. (from external carotid)

- Inferior thyroid a. (from thyrocervical trunk)

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3
Q

Thyroid gland is 2 symmetrical lobes fused by an ___________.

A

Isthmus

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4
Q

What veins drain the thyroid gland?

A

Plexus drains into superior, middle, and inferior thyroid veins (to IJV)

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5
Q

What innervates the thyroid gland?

Symp or parasymp?

A

Middle and inferior cervical ganglion

- Sympathetic NS

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6
Q

What’s the major functional unit of the thyroid gland?

A

Follicle

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7
Q

What is the name of the internal component of the thyroid gland follicle?
What’s in this compartment, generally?

A

Colloid

- TH precursor

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8
Q

What cells line the periphery of the thyroid gland’s colloid?
What occurs here?

A

Thyroid epithelial cells- where synthesis of TH occurs

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9
Q

In addition to thyroid epithelial cells, the thyroid gland houses one other important endocrine cell. Nestled in spaces between thyroid follicles are ____________ (2 names), which secrete _____________.

A
  • Parafollicular or C cells
  • Calcitonin (hormone)
    (Do not touch colloid; have many small granules on histology)
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10
Q

What are the major components of the colloid?

A
  • Large stores of thyroglobulin

- T3/T4

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11
Q

What’s the difference in the epithelial architecture of inactive follicles vs active follicles stimulated by TSH?

A
  • Inactive: squamous epithelium

- Active: cuboidal epithelium

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12
Q

Describe some of the properties of follicular cells in the thyroid gland. (not parafollicular)
(shape, surface features, spatial arrangement)

A
  • Cuboidal shape
  • Microvilli extend into colloid
  • Basement membrane – delineates follicle
  • Close to fenestrated capillaries
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13
Q

Thyroid hormones are iodothyryonines that require 2 precursors:

A
  1. Thyroglobulin (TG)

2. Iodide

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14
Q

Less than ____ of iodine daily results in a TH deficiency.

A

20 micrograms

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15
Q

How is most of the excessive iodide processed?

A

Secreted into the urine as iodine.

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16
Q

What is the Wolf-Chaikoff effect?

A

Autoregulation of iodide uptake:

  • An intrathyroid response that assures constancy of iodide storage in the face of changes in dietary iodide
  • Increases in iodide intake decrease gland xport (and vice versa)
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17
Q

How is the Wolf-Chaikoff effect taken advantage of clinically?

A

Very high iodide doses are used to rapidly shut down TH production in hyperthyroid pts

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18
Q

What’s another name for T4?

A

Thyroxine

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19
Q

What’s another name for T3?

A

Triiodothyronine

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20
Q

What’s the 1/2-life of T4?

T3?

A

T4: ~ a week
T3: ~ a day

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21
Q

How is T4 found in the blood?

A

Tightly bound to xport proteins (that’s why it has long 1/2-life)

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22
Q

Which binds to receptors w/high affinity, T4 or T3?

A

T3 much higher (T4 basically inactive form)

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23
Q

Thyroid hormones are more similar in characteristics to what hormone class?

A

Steroid hormones

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24
Q

What’s rT3?

A

Reverse triiodothyronine (biologically inactive)

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25
Q

Thyrotropin-releasing hormone (TRH) is released from what hypothalamic nucleus?

A

PVN

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26
Q

What provide tonic inhibition to thyrotropes (that release TSH) in the anterior pituitary?

A

*Dopamine and somatostatin

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27
Q

What types of receptors do TSH bind in the anterior pituitary?

A

GPCRs

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28
Q

T3/T4 provide negative feedback to the PVN in the hypo. What provides negative feedback to the thyroid hormone “sensor” in the anterior pituitary to stop release of TSH?

A

T3 (formed locally from T4 via type II deiodinase)

- Recall: also tonic inhibition by dopamine, somatostatin.

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29
Q

What’s the 2nd messenger cascade for TRH receptor stimulation in the ant pit?

A

GPCR -> PLC/DAG -> IP3/PKC -> ^ Ca2+ -> TSH release

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30
Q

What’s the 2nd messenger cascade for TSH receptor stimulation in the thyroid gland?

A

GPCR -> AC -> cAMP -> T4/T3 release

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31
Q

What is the first precursor for TH’s?

A

Tyrosine (on thyroglobulin)

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32
Q

What key enzyme is necessary in TH synthesis?

What 2 products are formed?

A
  • Thyroid peroxidase (TPO)

- Makes MIT, or adding another I- makes DIT

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33
Q

What 2 compounds combine in the thyroid follicle to make T4?

A

2x DIT

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34
Q

What 2 compounds combine to make T3?

Describe where the I’s are (outer and inner ring)

A

1x DIT + 1x MIT

Outer ring has 1 I-, inner ring has 2x I-

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35
Q

What’s the difference b/w reverse T3 (rT3) and T3?

A

T3’s outer ring has only 1 I-, rT3’s inner ring has only 1 I-

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36
Q

What drug inhibits thyroid peroxidase (TPO)?

What is it used to treat?

A
  • Carbimazole

- Tx for hyperthyroidism

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37
Q

Name the 7 steps of TH synthesis.

A
  1. Iodide trapping
  2. Transport
  3. Iodination (AKA organification)
  4. Conjugation
  5. Endocytosis
  6. Proteolysis
  7. Secretion
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38
Q

What’s the common factor of all 7 steps of TH synthesis?

What cell does it occur in, mostly?

A

All steps are stimulated by TSH

thyroid epithelial cell, though some middle steps occur in the colloid

39
Q

Thyroid follicle is functionally polarized. What is the basolateral surface exposed to?
What occurs on the basolateral side?

A
  • Blood

- Iodine uptake “trap”; TH release

40
Q

Thyroid follicle is functionally polarized. What is the apical surface exposed to?
What occurs on the apical side?

A
  • Colloid

- Organification, TH synthesis, etc.

41
Q

What occurs during step 1 of TH synthesis (iodide trapping)? (name the protein that’s involved)

A
  • TSH stimulates iodide (I-) trapping by increasing the activity of the NIS co-transporter in the basal membrane of the follicular epithelial cell.
    (NIS = sodium iodide symporter)
42
Q

What drug inhibits the NIS cotransporter in step 1 of TH synthesis?

A

Lithium

43
Q

What occurs during step 2 of TH synthesis (transport)?

name the protein that’s involved and the product

A

I- transported to follicular lumen and oxidized by thyroid peroxidase (TPO) to form iodine (I).
- TG xported to follicle lumen as well.

44
Q

What occurs during step 3 of TH synthesis (iodination/organification)?

A

Iodination of tyrosyl residues on thyroglobulin (via TPO)

45
Q

What occurs during step 4 of TH synthesis (conjugation)?

what is formed?

A

Conjugation of iodinated tyrosines to form T4 and T3-linked thyroglobulin (via TPO)

46
Q

What occurs during step 5 of TH synthesis (endocytosis)?

What ptn is involved?

A

Conjugated thyroglobulin with T4/T3 enters follicular epithelial cell. (has 4 attachment sites, can have MIT, DIT, T4 or T3.
- Packaged in endosomes (via megalin)

47
Q

What occurs during step 6 of TH synthesis (proteolysis)?

A

TG, MIT, DIT, T4, T3 released from vesicle (in thyroid epithelial cell)

48
Q

What occurs during step 7 of TH synthesis (secretion)?

A

T4/T3 secreted into circulation

49
Q

How does the radioactive iodide uptake scan work?

A
  • Used to determine function of thyroid gland
  • Iodide uptake in thyroid epithelial cell
  • Iodide is transported by the sodium iodide symporter (NIS)
  • Image = autoradiograph
50
Q

What are egs of some substances that can be xported by the NIS besides I-?

A
  • Radioactive iodide (131I, 123I) and anions like pertechnetate (TcO4)
51
Q

On a radioactive iodide uptake scan, what is a “hot nodule”?

What’s its clinical importance?

A

Area of increased follicular iodide uptake and TH synthesis.

- Usually benign

52
Q

On a radioactive iodide uptake scan, what is a “cold nodule”?
What’s its clinical importance?

A

Inactive/dysfunctional thyroid follicle.

- Can be benign or malignant

53
Q

In a radioactive iodide uptake scan, normal uptake is __% s/p 24 hrs.

A

25%

54
Q

In a radioactive iodide uptake scan, normal uptake is 25% s/p 24 hrs. What is the clinical threshold for hyper and hypothyroidism?

A
  • Hyper: greater than 60%

- Hypo: less than 5%

55
Q

In a radioactive iodide uptake scan, extreme stimulation of thyroid gland (high turnover) is seen in what condition?

A

Grave’s disease

56
Q

What is an organification defect? How could you test for it?

A

Iodide cannot be incorporate into tyrosine

- Test by blocking NIS w/inhibitor (i.e. perchlorate)

57
Q

What is a Type I deiodinase?
Where is it found?
What does it make? (activates or inactivates?)

A

Outer and inner ring deiodinase

  • Found in liver, kidney, thyroid, SkM
  • Makes T3 (activates) or rT3 (inactivates)
58
Q

What is a Type II deiodinase?
Where is it found?
What does it make? (activates or inactivates?)

A

Outer ring deiodinase

  • Found in brain, pituitary, placenta, cardiac m.
  • Always T3 (activates)
59
Q

What is a Type III deiodinase?
Where is it found?
What does it make? (activates or inactivates?)

A

Inner ring deiodinase

  • Found in brain, placenta, skin
  • Makes rT3 (inactivates)
60
Q

Which of the deiodinases forms most of the T3 in circulation?

A

Type I deiodinase

61
Q

What form of TH is produced and stored in the thyroid the most?

A

T4

62
Q

Wyhat serves as the TH “sensor” in the anterior pituitary?

A

Type II Deiodinase

63
Q

How much TH is bound in circulation?

A

99%+

64
Q

Name the proteins and the % of TH bound for each of the proteins that bind TH.

A
  • Thyroxine-binding globulin (TBG) (70%)
  • Albumin (15 – 25%)
  • Transthyretin (TTR) (10%)
65
Q

Which of the binding proteins for TH has the highest affinity?

A

TBG (but lowest concentration in the blood)

66
Q

How many AA’s is TBG?

A

394 AAs

unique: TBG can reversibly release T4 to target tissues

67
Q

Name a hormone and a disease the increase TBG.

A
  • Estrogen

- Hepatitis (it’s made in the liver)

68
Q

Name a hormone class and a disease the decrease TBG.

A
  • Steroids

- Nephrotic syndrome

69
Q

If a pt has a deficiency or excess of TBG, how is the total “free” concentration of TH altered?
This effect is different than what major binding protein?

A

No net change
- CBG (because 75% of cortisol is free)

(changes in TBG don’t usually effet bioavailable T3, but do affect total T4/T3 levels)

70
Q 
Describe the structure of the THR (TH receptor).
What hormone class is it similar to?
A

Nuclear receptor family
- Same as steroid hormones
- Forms heterodimers with
retinoic acid receptor (RXR) -> TS activation

71
Q

What cells types generally express THR?

A

All

72
Q

THRs have a (high/low) affinity, (high/low) capacity for T3.

They have a (high/low) affinity for T4.

A

T3: High affinity, low capacity
T4: Low affinity

73
Q

In general, what are the overall effects of TH?
(effect of metabolism, brain, receptors)

(read for now, leads into future questions)

A
  • Increases Basal Metabolic Rate (BMR)
  • Stimulates hepatic gluconeogenesis
  • Stimulates proteolysis
  • Stimulates lipolysis
  • *Overall increased energy/oxygen consumption, increased thermogenesis
  • Promotes Brain (CNS) Maturation
  • Increases β-adrenergic receptors: heart (B1), skeletal muscle, adipose tissue
74
Q

How is BMR affected by hyper and hypothyroidism?

A

Hyper: increased
Hypo: decreased

75
Q

How is carb metabolism and serum [glucose] affected by hyper and hypothyroidism?

A

Hyper: ^ GNG, ^ glycogenolysis, nl serum glc
Hypo: v GNG, v glycogenolysis, nl serum glc

76
Q

How is protein metabolism affected by hyper and hypothyroidism?

A

Hyper: ^ Synthesis, ^ proteolysis (m. wasting)
Hypo: v Synthesis, v proteolysis (no change)

77
Q

How is lipid metabolism and total serum [chol] affected by hyper and hypothyroidism?

A

Hyper: ^ lipogenesis, ^ lipolysis, v serum chol.
Hypo: v lipogenesis, v lipolysis, ^ serum chol.

78
Q

How is thermogenesis affected by hyper and hypothyroidism?

A

Hyper: increased (heat intolerant)
Hypo: decreased (cold intolerant)

79
Q

Some of the effects of T3 are futile cycles. What does this mean?

A

Occurs when two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat
- E.g. increasing GNG and increasing glycogenolysis simultaneously

80
Q

Why is lack of iodine salt the leading cause of mental retardation worldwide?

A

Because TH is critical for brain development

81
Q

What what causes cretinism? Provide the clinical presentation.

A

Iodine deficiency during development

  • Short stature/impaired bone formation
  • Mental retardation
  • Delayed motor development
82
Q

What are TH’s effects on the heart?

A
  • Increases CO
  • Resting HR and SV increase
  • Increases B1 adrenergic receptors
    (also decreases PVR)
83
Q

Hyperthyroidism can cause arrhythmias. What is the primary reason?

A

Due to increased beta-adrenergic receptors

84
Q

What is a goiter?

Is it more common in men or women?

A

Enlarged thyroid

- 3:1 women to men

85
Q

What pathology occurs w/Grave’s disease?

A

Autoimmune: antibodies created that stimulate the thyroid’s TSH receptors (LATS- long-acting thyroid stimulator), leading to elevated T3/T4

86
Q

What are the sx of Grave’s dz? (think)

A

Diffuse symmetrical goiters with hyperthyroid sx: tachycardia, exopthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting

87
Q

What pathology occurs w/Hashimoto’s thyroiditis?

A

Autoimmune destruction of thyroid follicular cells. AB’s made against TPO, TG (T3/T4 can’t be formed).

88
Q

What are the sx of Hashimoto’s thyroiditis? (think)

A

Diffuse goiter with hypothyroid sx: lethargy, fatigue, hair loss, cold intolerance, brittle nails decreased appetite, weight gain

89
Q

What is thyroid storm?

A

Hyperthyroid coupled with severe acute illness (emergency, life threatening situation)

90
Q

What are the sx of thyroid storm?

A

High fever, tachycardia, AMS, severe N/V/D, severe circulatory collapse resulting in death.

91
Q

How do you treat thyroid storm?

A
  • Propylthiouracil (PTU – only acute treatment, decreases TH produced by gland)
  • Carbimazole (methimazole)- inhibits TPO, used to treat hyperthyroism
  • Beta blockers to restore normal heart function
92
Q

What catalyzes all of the steps of TH synthesis that lead to thyroglobulin w/bound T3/T4/MIT/DIT (in some combination)?

A

*Thyroid peroxidase

93
Q

What two classes of protein are responsible for recycling I- and TG in the epithelial cell?

A

Proteases and deiodinases

FHB Hormone/Repro (16 decks)

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