Thyroid and the HPT Axis Flashcards Preview

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Flashcards in Thyroid and the HPT Axis Deck (98):
1

Where is the thyroid located?

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

2

What is the blood supply of the thyroid?

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

3

What is the innervation of the thyroid?

middle and inferior cervical ganglion (sympathetic NS)

4

What is the thyroid derived from?

Branchial pouch endoderm

5

What do thyroid follicles contain?

large storage of thyroglobulin (colloids)

6

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

inactive: flattened, squamous

active: cuboidal

stimulated by TSH

7

What is the functional unit of the thyroid?

the follicle

8

What is the follicle?

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

9

What is the major component of colloid?

thyroglobulin

10

What are parafollicular (C) cells?

produce calcitonin

11

What are iodothyronines?

thyroid hormones

12

What are the two precursors required for iodothyronines?

thyroglobulin (TG) and iodide

13

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

20 ug per day

14

What is the wolf-chaikoff effect?

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

15

How does the wolf-chaikoff effect work?

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

16

How can the wolf-chaikoff effect be used clinically?

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

17

What is the most preventable cause of mental retardation?

TH deficiency

18

What is T4?

thyroxine

19

What are some general functions of thyroxine?

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

tightly bound to transport proteins

binds to receptors with low affinity

20

What is T3?

Triiodothyronine

21

What are some general functions of triiodothyronine?

primary active form

most is converted intracellulary from T4

binds with high affinity, low capacity to receptor

22

What is rT3?

biologically inactive T3

23

What are the hypothalamic features of the HPT axis?

PVN

Thyrotropin releasing hormone (TRH)

negative feedback by T3/T4 synthesis

24

What are the pituitary features of the HPT axis?

Thyrotropes

TSH

negative feedback by intracellulary T3 release- thyroid sensor

tonically inactivated by dopamine and somatostatin

25

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

exposed to lumen (colloid)

thyroid hormone synthesis

iodination of TG

26

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

exposed to blood

iodine uptake "trap"

thyroid hormone release

27

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

TSH

28

What are the steps in thyroid hormone synthesis

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

29

What occurs during iodine trapping?

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

30

What occurs during transport?

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

thyroglobulin transported to lumen

31

What inhibits NIS?

lithium

32

What occurs during iodination?

iodination of tyrosyl residues on thyroglobulin (organification)

33

What occurs during conjugation?

conjugation of iodinated tyrosines to form T4 and T3 linked thyroglobulin

34

What inhibits TPO?

carbamizole

35

What are MIT and DIT?

modified tyrosines

1 DIT and 1 MIT = T3

2 DIT = T4

36

What is the difference between T3 and reverse T3?

DIT on inner ring = T3 (active)

DIT on outer ring = rT3 (inactive)

37

What occurs during endocytosis?

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

38

What occurs during proteolysis?

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

39

What occurs during secretion?

T4/T3 secreted into circulation

40

What is radioactive iodide uptake scan useful for?

can determine the function of the thyroid gland

41

What is a cold/hot nodule?

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

hot nodule: overactive follicle

42

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

25% after 24 hours

>60% hyperthyroid

43

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

hyperstimulated thyroid gland - Graves disease

44

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

iodine cannot be incorporated into tyrosine

test by blocking NIS with an inhibitor (perchlorate)

45

What does type I deiodinase do?

outer and inner ring deiodinase

46

Where is type I deiodinase found?

liver, kidney, thyroid, skeletal muscle

47

What is the primary source of T3 in the circulation?

Type I deiodinase

48

What does type II deiodinase do?

outer ring deiodinase for T4

49

Where is type II deiodinase found?

brain, pituitary, placenta, cardiac muscle

50

What does type III deiodinase do?

inner ring diodinase

51

Where is type III deiodinase found?

brain, placenta, skin

52

What is primarily synthesized and stored in the thyroid

T4

53

What percentage of T4 is converted to T3 peripherally?

80%

54

what affinity does T4 have?

low receptor affinity

55

What is the thyroid hormone "sensor" in the pituitary?

type II deiodinase

56

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

99%

57

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

thyroxine-binding globulin (TBG) - 70%

transthyretin (TTR) - 10%

albumin - 15-25%

58

What are the half lives of T4 and T3?

T4 tightly bound, half life of ~7 days

T3 half life 1 day

59

What family are TBG and TTR in?

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

60

Where are TBG and TTR made?

in the liver

61

What does T4 have the highest affinity for?

TBG

62

What increases TBG?

estrogen, hepatitis

63

What decreases TBG?

nephrotic syndrome, steroids

64

What is a result of increased or decreased TBG?

No change in "free" T4/T3!!

65

What is unique about TBG?

TBG can reversibly release T4 to target tissues

66

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

nuclear receptor family

67

What does THR form a complex with?

forms a heterodimer with retinoic acid receptor

68

Where is THR expressed?

in almost every cell type

69

What is the affinity and capacity to T3?

High affinity, low capacity

70

What is the affinity for T4?

low affinity - very low biological activity at physiological concentrations

71

What are the main physiological functions of thyroid hormone?

increases basal metabolic rate

promotes brain (CNS) maturation

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

72

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

stimulates hepatic gluconeogenesis

stimulates proteolysis

stimulates lipolysis

increased E/O2 consumption and an increase in thermogenesis

73

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

increasing mitochondrial activity

74

What would the BMR be in hypothyroidism?

decreased

75

What would the BMR be in hyperthyroidism?

increased

76

How would carbohydrate metabolism be affected in hypothyroidism?

decrease in gluconeogenesis and glycogenolysis with normal serum glucose

77

How would carbo metabolism change in hyperthyroidism?

increase in gluconeogenesis and glycogenolysis with normal serum glucose

78

How would protein metabolism change in hypothyroidism?

decreased synthesis, decreased proteolysis

79

How would protein metabolism change in hyperthyroidism?

increased synthesis, increased proteolysis

muscle wasting

80

How would lipid metabolism change in hypothyroidism?

decreased lipogenesis, decreased lipolysis, increased serum cholesterol

81

How would lipid metabolism change in hyperthyroidism?

increased lipogenesis, increased lipolysis, decreased serum cholesterol

82

How would thermogenesis change in hypothyroidism?

decreased (cold intolerant)

83

How would thermogenesis change in hyperthyroidism?

increased (heat intolerant)

84

What is T3 required for in the CNS?

normal brain development

neuronal cell migration/differentiation

myelination

synaptic transmission

85

What is cretinism and what is it caused by?

iodine deficiency during development

short stature/impaired bone formation

mental retardation

delayed motor development

86

What are the physiological effects of T3 on the heart?

increases cardiac output

resting heart rate and stroke volume increased

hyperthyroidism can cause arrhythmias due to increased beta adrenergic receptors

87

What is a goiter?

hyperproliferation of cells due to hyperstimulation of TSH

88

What can cause a goiter?

cancer - 3:1 women:men

hyperthyroid - Grave's disease

hypothyroid - Hashimoto's thyroiditis, iodine deficiency

89

What is Grave's disease?

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

90

What is elevated in Grave's?

T3/T4

91

What is the presentation and symptoms of Grave's?

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

92

What is Hashimoto's thyroiditis?

autoimmune destruction of the thyroid follicles

93

What are Ab directed against in Hashimoto's?

TPO, TG

94

What is the presentation and symptoms of Hashimoto's?

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

95

What is a thyroid storm?

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

96

What are the symptoms of thyroid storm?

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

97

What is the treatment of thyroid storm?

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

Carbimazole (methimazole) - inhibit TPO

Beta blockers to restore normal heart function

98

What is the cause of circulatory collapse in thyroid storm?

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