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FHB Block 4 > Thyroid and the HPT Axis > Flashcards

Thyroid and the HPT Axis Flashcards

1
Q

Where is the thyroid located?

A

anterior to the cricoid cartilage, two symmetrical lobes fused by isthmus

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2
Q

What is the blood supply of the thyroid?

A

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

venous plexus on surface gives rise to superior, middle, and inferior thyroid veins which drain into the internal jugular

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3
Q

What is the innervation of the thyroid?

A

middle and inferior cervical ganglion (sympathetic NS)

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4
Q

What is the thyroid derived from?

A

Branchial pouch endoderm

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5
Q

What do thyroid follicles contain?

A

large storage of thyroglobulin (colloids)

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6
Q

What is the appearance of inactivated vs activated thyroid cells, and what activates them?

A

inactive: flattened, squamous
active: cuboidal

stimulated by TSH

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7
Q

What is the functional unit of the thyroid?

A

the follicle

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8
Q

What is the follicle?

A

epithelial cells with microvilli extending into a lumen filled with colloid which forms 30% of the thyroid mass

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9
Q

What is the major component of colloid?

A

thyroglobulin

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10
Q

What are parafollicular (C) cells?

A

produce calcitonin

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11
Q

What are iodothyronines?

A

thyroid hormones

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12
Q

What are the two precursors required for iodothyronines?

A

thyroglobulin (TG) and iodide

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13
Q

What is the lower limit of iodide intake that will result in ormone deficiency?

A

20 ug per day

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14
Q

What is the wolf-chaikoff effect?

A

an autoregulatory intrathyroidal response that maintains iodide stores in the face of of changes in dietary iodide

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15
Q

How does the wolf-chaikoff effect work?

A

increases in dietary iodide decrease gland transport and hormone synthesis and vice versa

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16
Q

How can the wolf-chaikoff effect be used clinically?

A

give high doses of iodide to shut down thyroid hormone production in hyperthyroid pts

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17
Q

What is the most preventable cause of mental retardation?

A

TH deficiency

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18
Q

What is T4?

A

thyroxine

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19
Q

What are some general functions of thyroxine?

A

long half life in plasma (~7-8 days)

tightly bound to transport proteins

binds to receptors with low affinity

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20
Q

What is T3?

A

Triiodothyronine

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21
Q

What are some general functions of triiodothyronine?

A

primary active form

most is converted intracellulary from T4

binds with high affinity, low capacity to receptor

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22
Q

What is rT3?

A

biologically inactive T3

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23
Q

What are the hypothalamic features of the HPT axis?

A

PVN

Thyrotropin releasing hormone (TRH)

negative feedback by T3/T4 synthesis

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24
Q

What are the pituitary features of the HPT axis?

A

Thyrotropes

TSH

negative feedback by intracellulary T3 release- thyroid sensor

tonically inactivated by dopamine and somatostatin

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25
Q

What is the apical surface of the thyroid follicles exposed to, and what does it do?

A

exposed to lumen (colloid)

thyroid hormone synthesis

iodination of TG

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26
Q

What is the basolateral surface of the thyroid follicles exposed to, and what does it do?

A

exposed to blood

iodine uptake “trap”

thyroid hormone release

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27
Q

What are all the steps in thyroid hormone biosynthesis mediated by?

A

TSH

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28
Q

What are the steps in thyroid hormone synthesis

A
  1. iodine trapping
  2. transport
  3. iodination
  4. conjugation
  5. endocytosis
  6. proteolysis
  7. secretion
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29
Q

What occurs during iodine trapping?

A

TSH stimulates iodide trapping by increasing activity of NIS cotransporter in the basoateral membrane of the follicular epithelial cell

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30
Q

What occurs during transport?

A

Iodide transported to follicular lumen and oxidized by thyroid peroxidase (TPO) to form iodine

thyroglobulin transported to lumen

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31
Q

What inhibits NIS?

A

lithium

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32
Q

What occurs during iodination?

A

iodination of tyrosyl residues on thyroglobulin (organification)

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33
Q

What occurs during conjugation?

A

conjugation of iodinated tyrosines to form T4 and T3 linked thyroglobulin

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34
Q

What inhibits TPO?

A

carbamizole

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35
Q

What are MIT and DIT?

A

modified tyrosines

1 DIT and 1 MIT = T3

2 DIT = T4

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36
Q

What is the difference between T3 and reverse T3?

A

DIT on inner ring = T3 (active)

DIT on outer ring = rT3 (inactive)

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37
Q

What occurs during endocytosis?

A

conjugated thyroglobulin with T4/T3 enters the follicular endothelial cell and is packaged in endosomes

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38
Q

What occurs during proteolysis?

A

TG, MIT, DIT, T3, T4 released from vesicle

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39
Q

What occurs during secretion?

A

T4/T3 secreted into circulation

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40
Q

What is radioactive iodide uptake scan useful for?

A

can determine the function of the thyroid gland

41
Q

What is a cold/hot nodule?

A

cold nodule: non-functioning follicles that aren’t taking up iodine –> more predictive of a malignancy

hot nodule: overactive follicle

42
Q

What is a normal iodide uptake and what are pathological scenarios?

A

25% after 24 hours

> 60% hyperthyroid

43
Q

When is accelerated turnover seen, and what is a disease associated with this?

A

hyperstimulated thyroid gland - Graves disease

44
Q

What is the issue with a organification defect, and how could you test this?

A

iodine cannot be incorporated into tyrosine

test by blocking NIS with an inhibitor (perchlorate)

45
Q

What does type I deiodinase do?

A

outer and inner ring deiodinase

46
Q

Where is type I deiodinase found?

A

liver, kidney, thyroid, skeletal muscle

47
Q

What is the primary source of T3 in the circulation?

A

Type I deiodinase

48
Q

What does type II deiodinase do?

A

outer ring deiodinase for T4

49
Q

Where is type II deiodinase found?

A

brain, pituitary, placenta, cardiac muscle

50
Q

What does type III deiodinase do?

A

inner ring diodinase

51
Q

Where is type III deiodinase found?

A

brain, placenta, skin

52
Q

What is primarily synthesized and stored in the thyroid

A

T4

53
Q

What percentage of T4 is converted to T3 peripherally?

A

80%

54
Q

what affinity does T4 have?

A

low receptor affinity

55
Q

What is the thyroid hormone “sensor” in the pituitary?

A

type II deiodinase

56
Q

What percent of thyroid hormone is bound to protein in the blood?

A

99%

57
Q

What are the transport proteins that bind thyroid hormone in the blood?

A

thyroxine-binding globulin (TBG) - 70%

transthyretin (TTR) - 10%

albumin - 15-25%

58
Q

What are the half lives of T4 and T3?

A

T4 tightly bound, half life of ~7 days

T3 half life 1 day

59
Q

What family are TBG and TTR in?

A

serpine protease inhibitors (but not a serpine inhibitor) - same as CBG

60
Q

Where are TBG and TTR made?

A

in the liver

61
Q

What does T4 have the highest affinity for?

A

TBG

62
Q

What increases TBG?

A

estrogen, hepatitis

63
Q

What decreases TBG?

A

nephrotic syndrome, steroids

64
Q

What is a result of increased or decreased TBG?

A

No change in “free” T4/T3!!

65
Q

What is unique about TBG?

A

TBG can reversibly release T4 to target tissues

66
Q

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

A

nuclear receptor family

67
Q

What does THR form a complex with?

A

forms a heterodimer with retinoic acid receptor

68
Q

Where is THR expressed?

A

in almost every cell type

69
Q

What is the affinity and capacity to T3?

A

High affinity, low capacity

70
Q

What is the affinity for T4?

A

low affinity - very low biological activity at physiological concentrations

71
Q

What are the main physiological functions of thyroid hormone?

A

increases basal metabolic rate

promotes brain (CNS) maturation

increases beta adrenergic receptors (transcription): heart, skeletal muscle, adipose tissue

72
Q

How does thyroid hormone stimulate an increase in basal metabolic rate, and what is the overall effect?

A

stimulates hepatic gluconeogenesis

stimulates proteolysis

stimulates lipolysis

increased E/O2 consumption and an increase in thermogenesis

73
Q

How does T3 stimulate an increase in O2 consumption and thermogenesis?

A

increasing mitochondrial activity

74
Q

What would the BMR be in hypothyroidism?

A

decreased

75
Q

What would the BMR be in hyperthyroidism?

A

increased

76
Q

How would carbohydrate metabolism be affected in hypothyroidism?

A

decrease in gluconeogenesis and glycogenolysis with normal serum glucose

77
Q

How would carbo metabolism change in hyperthyroidism?

A

increase in gluconeogenesis and glycogenolysis with normal serum glucose

78
Q

How would protein metabolism change in hypothyroidism?

A

decreased synthesis, decreased proteolysis

79
Q

How would protein metabolism change in hyperthyroidism?

A

increased synthesis, increased proteolysis

muscle wasting

80
Q

How would lipid metabolism change in hypothyroidism?

A

decreased lipogenesis, decreased lipolysis, increased serum cholesterol

81
Q

How would lipid metabolism change in hyperthyroidism?

A

increased lipogenesis, increased lipolysis, decreased serum cholesterol

82
Q

How would thermogenesis change in hypothyroidism?

A

decreased (cold intolerant)

83
Q

How would thermogenesis change in hyperthyroidism?

A

increased (heat intolerant)

84
Q

What is T3 required for in the CNS?

A

normal brain development

neuronal cell migration/differentiation

myelination

synaptic transmission

85
Q

What is cretinism and what is it caused by?

A

iodine deficiency during development

short stature/impaired bone formation

mental retardation

delayed motor development

86
Q

What are the physiological effects of T3 on the heart?

A

increases cardiac output

resting heart rate and stroke volume increased

hyperthyroidism can cause arrhythmias due to increased beta adrenergic receptors

87
Q

What is a goiter?

A

hyperproliferation of cells due to hyperstimulation of TSH

88
Q

What can cause a goiter?

A

cancer - 3:1 women:men

hyperthyroid - Grave’s disease

hypothyroid - Hashimoto’s thyroiditis, iodine deficiency

89
Q

What is Grave’s disease?

A

autoimmune - Ab stimulate TSH receptor (Long Acting-Thyroid Stimulator) (LATS)

90
Q

What is elevated in Grave’s?

A

T3/T4

91
Q

What is the presentation and symptoms of Grave’s?

A

diffuse, symmetrical goiter with hyperthyroid symptoms: tachycardia, opthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting

92
Q

What is Hashimoto’s thyroiditis?

A

autoimmune destruction of the thyroid follicles

93
Q

What are Ab directed against in Hashimoto’s?

A

TPO, TG

94
Q

What is the presentation and symptoms of Hashimoto’s?

A

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

95
Q

What is a thyroid storm?

A

hyperthyroid coupled with acute illness (hyperthyroid + infection or trauma)

96
Q

What are the symptoms of thyroid storm?

A

high fever, tachycardia, altered mental status, severe nausea, vomiting, and diarrhea, severe circulatory collapse

97
Q

What is the treatment of thyroid storm?

A

Propylthiouracil (PTU – only acute treatment) - stops TH production

Carbimazole (methimazole) - inhibit TPO

Beta blockers to restore normal heart function

98
Q

What is the cause of circulatory collapse in thyroid storm?

A

TH + Catecholamines results in massive vasodilation and perfusion of all tissues at once

FHB Block 4 (13 decks)

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