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Part 3 – PM3B > (PM3B) Thyroid Axis > Flashcards

(PM3B) Thyroid Axis Flashcards

1
Q

What is TRH?

A

Thyrotropin Releasing Hormone

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2
Q

What is TSH?

A

Thyroid Stimulating Hormone

Can also be called ‘thyrotropin stimulating hormone’

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3
Q

Where is TRH secreted?

A

Parvocellular neurosecretory cells in the hypothalamus

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4
Q

What is the inflow of blood called in the pituitary gland?

A

Superior hypophyseal artery

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5
Q

Which organs are involved in the regulation of thyroid hormone release?

A

(1) Hypothalamus
(2) Anterior pituitary gland
(3) Thyroid

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6
Q

Which organ releases TRH?

A

Hypothalamus

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7
Q

Which organ releases TSH?

A

Thyroid

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8
Q

Which hormones provide negative feedback on the regulation of thyroid hormone?

A

(1) TSH
(2) T3
(3) T4

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9
Q

Which organ releases T3 and T4?

A

Thyroid

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10
Q

What hormone(s) does the thyroid produce?

A

(1) T3

(2) T4

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11
Q

What hormone(s) does the anterior pituitary gland produce?

A

TSH

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12
Q

What hormone(s) does the hypothalamus produce?

A

TRH

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13
Q

Which organs does the negative feedback of T3/T4 effect?

A

(1) Anterior pituitary gland

(2) Hypothalamus

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14
Q

What is the cascade of events in thyroid hormone regulation?

A

(1) Hypothalamus produces TRH
(2) TRH stimulates anterior pituitary gland
(3) Anterior pituitary gland produces TSH
(4) TSH stimulates thyroid
(5) Thyroid produces T3 and T4
(6) T3 and T4 enter bloodstream
(7) Effect of T3 and T4 on target cells

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15
Q

What is the mechanism of action of TSH?

A

TSH binds to a GPCR of a thyroid follicle epithelial cell. This triggers two pathways.

(1) Activates adenylate cyclase - leads to a cAMP/ PKA-dependent pathway
(2) Activates phospholipase C - leads to PI turnover and production of DAG and IP3 (inositol triphosphate)

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16
Q

What is the structure of a thyroid follicle?

A

Hollow sphere
Comprised of epithelial cells surrounding a lumen which is filled with a gelatinous colloid
This gelatinous colloid contains thyroglobulin

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17
Q

How does the structure of a thyroid follicle change when the follicle is UNDERactive?

A

The lumen enlarges

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18
Q

How does the structure of a thyroid follicle change when the follicle is OVERactive?

A

The lumen reduces in size

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19
Q

What does a ‘C-cell’ in a thyroid follicle do?

A

Produces calcitonin

This is involved in calcium balance

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20
Q

Where is thyroglobulin made?

A

Synthesised in the thyroid follicular cells

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21
Q

What does thyroglobulin contain large concentrations of?

A

Tyrosine

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22
Q

Where can tyrosine be found in large concentrations?

A

Thyroglobulin

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23
Q

How does iodide (I-) enter the lumen?

A

Blood -> Follicular cells
via active transport
Then is transported to lumen

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24
Q

What converts iodide to ‘free iodine’?

A

Thyroid Peroxidase

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25
Q

Where does thyroid peroxidase convert iodide to free iodine?

A

In the lumen of thyroid follicular cells

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26
Q

What type of iodine is included in the tyrosine residues?

A

Free iodine

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27
Q

What atom is included in the tyrosine residues?

A

Free iodine

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28
Q

Where are tyrosine residues found?

A

Thyroglobulin molecules

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29
Q

What is MIT?

A

Mono-iodotyrosine (MIT)

Has 1 iodine per tyrosine (T1)

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30
Q

What is DIT?

A

Di-iodotyrosine (DIT)

Has 2 iodines per tyrosine (T2)

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31
Q

DIT + DIT = ?

A

T4

Thyroxine

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32
Q

MIT + DIT = ?

A

T3

Triodothyronine

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33
Q

MIT + MIT = ?

A

Nothing, they do not couple.

T2 (DIT) cannot be synthesised this way.

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34
Q

What is the first stage of thyroid hormone synthesis?

A

(1)
Iodide (I-) trapping.

Actively transported into follicles from blood.

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35
Q

What is the second stage of thyroid hormone synthesis?

A

(2)
Synthesis of TBG

TBG = Thyroxine-Binding Globulin

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36
Q

What is the third stage of thyroid hormone synthesis?

A

(3)
Oxidation of iodide to iodine (I2)

It is initiated by thyroid peroxidase

37
Q

What is the fourth stage of thyroid hormone synthesis?

A

(4)
Iodination of tyrosine

Iodine (I2) is incorporated into tyrosine residues

38
Q

What is the fifth stage of thyroid hormone synthesis?

A

(5)

Coupling of MIT and DIT molecules to form T3 and T4

39
Q

What is the sixth stage of thyroid hormone synthesis?

A

(6)
Pinocytosis and digestion of colloid.

Lysosomal enzymes digest iodinated thyroglobulin

40
Q

What is the seventh stage of thyroid hormone synthesis?

A

(7)
Secretion of thyroid hormones

T3 and T4 diffuse through plasma membrane into blood

41
Q

What is the eighth stage of thyroid hormone synthesis?

A

(8)

T3 and T4 (thyroid hormones) are transported through the blood to target cells

42
Q

How many stages are there in thyroid hormone synthesis?

43
Q

What is TBG?

A

Thyroid-binding globulin

44
Q

What does TBG do? Why?

A

(1) Allows for T3/ T4 binding - prevents urinary excretion*
(2) Buffers against acute changes of thyroid function

*T3 and T4 have poor solubility in water (blood)

45
Q

What percentages of overall secreted thyroid hormone do T3 and T4 comprise?

A 
T3 = 10%
T4 = 90%
46
Q

Which thyroid hormone is more potent? Why?

A

T3 is about 4x more potent

T3 binds to the intracellular thyroid hormone receptor with greater affinity

47
Q

What happens to most T4 in the target tissue?

A

Most is converted to T3 by removing one iodine

48
Q

Which organs are particularly important for activating the conversion of T4 to T3?

A

Liver and kidneys

49
Q

Where do T3 and T4 bind?

A

Intracellular thyroid hormone receptor

50
Q

Are thyroid hormones hydro/ lipophilic?

A

Lipophilic

Hence their need for binding to TBG in the blood

51
Q

What molecule can thyroid hormones bind to in the blood to prevent urinary excretion?

A

(1) TBG: Thyroid-binding globulin

(2) Albumin

52
Q

What are the effects of thyroid hormone?

A

(1) Metabolic Rate
(2) Cardiovascular system
(3) Nervous system
(4) Growth and maturation

53
Q

How does thyroid hormone affect metabolic rate?

A

Increases basal metabolic rate

54
Q

How does thyroid hormone affect the CVS?

A

(1) Increases heart rate

(2) Increases force of heart contraction

55
Q

How does thyroid hormone affect the NS?

A

(1) Increases activity of sympathetic NS

(2) Increases sensitivity to catecholamines - such as adrenaline or dopamine

56
Q

Name 2 examples of catecholamines

A

(1) Adrenaline

(2) Dopamine

57
Q

How does thyroid hormone affect growth and maturation?

A

(1) Embyro development
(2) CNS development
(3) Linear growth - increases affect of growth hormone

58
Q

How many systems/ processes does thyroid hormone affect?

A

Four

Growth + maturation, NS, CVS, and metabolism

59
Q

What is goitre? What causes it?

A

Hypertrophy of thyroid gland

Over-stimulation by TSH (Thyroid-stimulating hormone)

60
Q

How common is goitre?

A

Approximately 2% of the population

61
Q

What conditions are associated with goitre?

A

Either hypo/ hyperthyroidism

Often autoimmune

62
Q

What are the common symptoms/ features of hypothyroidism?

A

(1) Weight gain
(2) Intolerance of the cold
(3) Tiredness/ fatigue
(4) Goitre
(5) Hyperlipidaemia
(6) Bradycardia
(7) Dry/ thick skin
(8) Depression/ poor memory
(9) Constipation

63
Q

What symptoms/ features are commonly present in children with hypothyroidism?

A

(1) Cretinism
(2) Obesity
(3) Stunted growth
(4) Mental retardation - irreversible foetal brain damage

64
Q

How is hypothyroidism detected early in children?

A

Routine elevated TSH checks for neonates

High TSH indicates low T3/T4 - limited negative feedback on hypothalamus and pituitary

65
Q

How is hypothyroidism treated?

A

Lifelong levothyroxine therapy

Dose: 150mcg/ day

66
Q

How is levothyroxine administered? What advice applies?

A

Orally, as tablets

Take on an empty stomach - increases absorption

67
Q

What does levothyroxine imitate?

A

Natural T4

68
Q

What exception to treatment with levothyroxine is there?

A

Chronic dietary iodine deficiency

Treated with supplementary iodine in diet

69
Q

Why is T4 (levothyroxine) chosen over T3 in the UK?

A

Dosing is not critical

T4 has a long half-life

70
Q

When is T3 (liothyronine) recommended?

A

When faster-acting is required - such as myxedema coma/ preparation for ablation with radioactive iodine

71
Q

What is a primary cause of hypo/ hyperthyroidism?

A

Failure of the thyroid gland directly

72
Q

What is a secondary cause of hypo/ hyperthyroidism?

A

Failure of anterior pituitary gland

73
Q

What is a tertiary cause of hypo/ hyperthyroidism?

A

Failure of the hypothalamus

74
Q

What are the effects of failure of the thyroid gland in hypothyroidism?

A

(1) Low T3/ T4
(2) High TSH
(3) Goitre

75
Q

What are the effects of anterior pituitary failure in hypothyroidism?

A

(1) Low T3/ T4
(2) Low TSH (and TRH)
(3) No goitre

Has the same symptoms as hypothalamic (tertiary) failure

76
Q

What are the effects of hypothalamic failure in hypothyroidism?

A

(1) Low T3/ T4
(2) Low TSH (and TRH)
(3) No goitre

Has the same symptoms as anterior pituitary (secondary) failure

VERY RARE

77
Q

What are 3 different types of primary thyroid failure in hypothyroidism?

A

(1) Thyroid failure
(2) Autoimmune damage to gland (Hashimoto’s thyroiditis)
(3) Chronic lack of dietary iodine

78
Q

Is hyperthyroidism common?

A

Yes

Affects approx. 2% of women

79
Q

What are common symptoms/ features of hyperthyroidism?

A

(1) Weight loss
(2) Nervousness
(3) Heat intolerance
(4) High cardiac output
(5) Hand tremors
(6) Eyeball protrusion - exophthalmos

80
Q

(1) What is a primary cause of hyperthyroidism?

(2) What are its effects?

A

(1) Hypersecreting tumour
(2)
- High T3/ T4
- Low TSH
- No goitre

81
Q

(1) What is a secondary cause of hyperthyroidism?

(2) What are its effects?

A 
(1) Excess anterior pituitary/ hypothalamic secretion
(2)
- High TRH/ TSH
- High T3 and T4
- Goitre
82
Q

What are the effects of Graves’ disease?

A

(1) High T3/ T4
(2) Low TSH
(3) Goitre

83
Q

What are the treatment options for hyperthyroidism?

A

Anti-thyroid drugs to interfere with thyroid hormone synthesis/ surgical resection/ thyroid ablation using iodine

84
Q

What is the mechanism of action of an anti-thyroid drug?

A

Blocks the thyroid peroxidase enzyme

Prevents iodination of thyroglobulin

85
Q

What is first line treatment for hyperthyroidism?

A

Carbimazole

Propylthiouracil is given if 1st line not tolerated

86
Q

What are complications of hyperthyroidism treatment?

A

Often results in thyroid hypertrophy (goitre)

87
Q

When are drugs normally used in hyperthyroidism?

A

Prior to surgical resection (thyroidectomy)

88
Q

(1) What is a common side-effect of carbimazole?

(2) How is it treated?

A

(1) Rash

(2) Antihistamine + switch to propylthiouracil

89
Q

What is an uncommon side-effect of carbimazole?

A

Suppression in bone marrow

Presents as sore throat, mouth ulcers, and fever

Part 3 – PM3B (32 decks)

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