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Endocrinology > Lecture 7: Thyroid and HPT Axis > Flashcards

Lecture 7: Thyroid and HPT Axis Flashcards

1
Q

Where is the thyroid?

A

anterior to the cricoid cartilage

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2
Q

Describe the morphology of the thyroid

A

2 symmetrical lobes fused by isthmus

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3
Q

What is the blood supply to the thyroid?

A

superior (ext. carotid) and inferior (thyrocervical trunk) thyroid

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4
Q

How is the epithelium arranged in the thyroid?

A

in follicles that contain large storage of thyroglobulin (colloid)

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5
Q

Inactive, flattened follicles are __________ epithelium

A

squamous

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6
Q

Once stimulated by _____, follicles become active

A

TSH

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7
Q

Active follicles transform to ____________ epithelium

A

cuboidal

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8
Q

The lumen of the thyroid is filled with ___________ (30% of mass)

A

colloid

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9
Q

Parafollicular cells (C cells) produce ____________

A

calcitonin

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10
Q

Describe the morphology of the follicular cells

A

cuboidal shape
microvilli extend into colloid
close to fenestrated capillaries

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11
Q

Do the parafollicular cells touch the colloid?

A

NO

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12
Q

What are the 2 precursors of thyroid hormones (or iodothyronines?)

A

1) thyroglobulin (TG)

2) iodide

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13
Q

What is the bare minimum of iodide intake to avoid thyroid hormone deficiency?

A

20ug/day

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14
Q

If the average iodide intake is 400ug/day and we only need 20, where does the rest go?

A

excreted into urine

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15
Q

What is the Wolf-Chaikoff Effect?

A

intrathyroidal response that assures constancy of iodide storage in the face of changes in dietary iodide\

AUTOREGULATION OF IODIDE INTAKE

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16
Q

Increases in iodide intake __________ (increases/decreases) gland transport and hormone synthesis

A

decrease

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17
Q

What is a clinical tool to rapidly shut down thyroid hormone production in hyperthyroid patients?

A

Very high iodide doses

basically at really high doses of iodide, the thyroid does not take up a lot of it

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18
Q

What are the 3 thyroid hormones?

A

1) Thyroxine (T4)
2) Triiodothyroinin (T3)
3) Reverse triiodothyronine (rT3)

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19
Q

Which thyroid hormone binds to its receptor with low affinity? With high?

A

T4 –> low affinity

T3 –> high affinity

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20
Q

What form of thyroid hormone is found circulating?

A

T4 (tightly bound to transport proteins in blood)

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21
Q

Where is T3 found?

A

intracellularly (converted from T4)

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22
Q

What is the active form of thyroid hormone?

A

T3

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23
Q

What does rT3 do?

A

nothing, biologically inactive

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24
Q

Which hormone has a long half life, T4 or T3?

A

T4

7-8 days

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25
Q

What is the HPT axis?

A

Hypothalamus (TRH) - Pituitary (TSH) -Thyroid (T3/T4)

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26
Q

Where in the hypothalamus is TRH made?

A

PVN

gets negative feedback by T4/T3

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27
Q

What is the thyroid sensor in the pituitary?

A

intracellular T3 (imposes negative feedback)

Type II deiodinase

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28
Q

What inhibits TSH in the pituitary?

A

somatostatin, dopamine

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29
Q

Describe the functional polarization of the thyroid follicle?

A

Apical: exposed to lumen (colloid) where hormone synthesis occurs; iodination of TG

Basolateral: exposed to blood; iodine uptake “trap”
where thyroid hormone is released

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30
Q

Where are the thyroid hormones made?

A

colloid

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31
Q

Where are hormones iodinized?

A

follicle

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32
Q

Describe the first step of thyroid hormone synthesis

A

1) Iodide trapping: TSH stimulates iodide trapping by increasing activity of NIS co-transporter in basal membrane of follicular epithelial cell

33
Q

What carries iodide into the follicular epithelial cell?

A

NIS co-transporter

stands for sodium, iodide symporter

34
Q

Once iodide has been taken up by the cell, what is the second step in thyroid hormone synthesis?

A

2) I- is transported to the follicular lumen and oxidized by thyroid peroxidase (TPO) to form iodine (I)

35
Q

What oxidizes iodide to iodine?

A

thyroid peroxidase (TPO)

36
Q

All steps in thyroid hormone synthesis are mediated by ____

A

TSH

37
Q

What inhibits NIS? the symporter responsible for iodide uptake?

A

lithium

can be used to treat hyperthyroidism

38
Q

After iodide is transported to the apical membrane and converted to iodine, what happens?

A

tyrosyl residules on thyroglobulin are iodinated

ORGANIFICATION

39
Q

What does MIT and DIT mean?

A 
MIT = one thyroid residue iodinated
DIT = two thyroid residues iodinated
40
Q

What happens after iodination?

A

conjugation of iodinated tyrosines to form T4 and T3 linked thyroglobulin

41
Q

What inhibits thyroid peroxidase (TPO)?

A

carbimaxole (cannot convert iodide to iodine –> cannot iodinate hormones)

42
Q

What is the chemical make up of T4? (in terms of DIT/MIT)

A

2 DIT

43
Q

What is the chemical make up of T3?

A

1 MIT + 1 DIT

44
Q

Which hormone has the outer ring DIT and inner ring MIT?

A

rT3

45
Q

Once T3/T4 are made and iodinated, what happens?

A

endocytosis (mediated by MEGALIN)

conjugated thyroglobulin with T4/T3 enters follicular epithelial cell
packaged in endosomes

46
Q

What happens after endocytosis?

A

proteolyis (TG, MIT, DIT, T4, and T3 released from vesicle)

then secretion into circulation

47
Q

How much thyroid hormone is stored in colloid?

A

2-3 months worth

48
Q

Which protein assists with endocytosis of conjugated thyroglobulin?

A

megalin

49
Q

What is the purpose of radioactive iodide uptake scans?

A

to measure iodide uptake in thyroid epithelial cell (via NIS)

50
Q

What do black results indicate on radioactive thyroid scan?

A

sites of uptake (hot nodule)

more black area –> indicative of Graves
cold nodules are more indicative of thyroid cancer than hot

51
Q

What is normal iodide uptake?

A

25% after 24 hours

dont have more because of Wolf Chaikoff

52
Q

What is iodide uptake in hyperthyroid patients? Hypothyroid patients?

A

> 60%

hypo:

53
Q

How do you test for an organification defect?

A

block NIS (with perchlorate) so iodide cannot be taken up

should still be able to convert iodide to iodine (TPO still functional)

54
Q

Why do thyroid hormones have different effects on different tissues?

A

deiodinases

55
Q

Where are Type I deiodinases?

A

Liver, kidney, thyroid, skeletal muscle

primary source of T3 in circulation due to their OUTER and INNER ring deiodinase

56
Q

Where are Type II deiodinases?

A

brain, pituitary, placenta, cardiac muscle

outer ring deiodinase

57
Q

Where are Type III deiodinases?

A

brain, placenta, skin

inner ring deiodinase

58
Q

What percentage of T4 is deiodinated to T3?

A

80%

59
Q

What are the transport proteins for thyroid hormone?

A

1) thyroxine-binding globulin (TBG) 70%
2) Transthyretin (TTR) 10%
3) Albumin (15-25%)

60
Q

Which has a longer half life, T4 or T3?

A

T4 (7-8 days)

T3 (1 day)

61
Q

What does T4 bind to with the highest affinity?

A

TBG (but it is in lowest concentration)

62
Q

What increases TBG?

A

estrogen, hepatitis

63
Q

What decreases TBG?

A

nephrotic syndrome, steroids

64
Q

How is T4 released at target tissues?

A

cleaved by protease (reversible reaction)

65
Q

What kind of receptor is the the thyroid hormone receptor (THR)?

A

nuclear (same as steroids; forms heterodimers with retinoic acid receptor)

66
Q

Where is THR expressed?

A

nearly every cell type

67
Q

Which hormone does THR have the highest affinity for?

A

T3 (low capacity thought)

low affinity for T4

68
Q

What is the physiological function of T3?

A

1) Increase basal metabolic rate (BMR)

2) Promote brain (CNS) maturation (increases beta-adrenergic receptors)

69
Q

How does T3 increase BMR?

A
  • stimulates hepatic gluconeogenesis, proteolysis, lipolysis

Increases energy/oxygen consumption; increases thermogenesis (hyperthyroid patients are heat intolerant)

70
Q

What does T3 do in terms of brain development?

A
  • promotes neuronal cell migration
  • myelination
  • synaptic transmission
71
Q

What is cretinism?

A

iodine deficiency during development

short stature, mental retardation

72
Q

Why are hyperthyroid patients at risk for arrhythmias?

A

increased beta-adrenergic receptors (resting heart rate and stroke volume)

T3 increases cardiac output (increases stroke volume and resting heart rate)

73
Q

Is thyroid cancer more common in women or men?

A

WOMEN (3:1)

74
Q

How do goiters form without iodine?

A

excessive production of TSH, get hyper active follicular cells causing a goiter

75
Q

Label these hyper or hypothyroid: Graves, Hashimotos thyroiditis, iodine deficiency

A

HYPER: Graves

HYPO: Hashimotos thyroiditis, iodine deficiency

76
Q

What is the cause of Graves?

A

autoimmune - antibodies stimulate TSH receptor (called Long-Acting Thyroid Stimulator - LATS) leading to elevated levels of T4/T3 (thinks it is always on)

77
Q

What is Hashimotos Thyroiditis?

A

autoimmune destruction of thyroid follicles (antibodies against TPO (cannot convert iodide to iodine) and TG

cold intolerance

78
Q

What is thyroid storm??

A

Hyperthyroid coupled with severe acute illness (tachycardic, altered mental status, circulatory collapse)

treat with carbimazole and beta blockers (restore heart rate)

Endocrinology (16 decks)

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