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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

anterior pituatry gland

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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

How does iodide (I-) enter the lumen?

A

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

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23
Q

What converts iodide to ‘free iodine’?

A

Thyroid Peroxidase

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24
Q

Where does thyroid peroxidase convert iodide to free iodine?

A

In the lumen of thyroid follicular cells

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25
Q

What type of iodine is included in the tyrosine residues?

A

Free iodine

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26
Q

Where are tyrosine residues found?

A

Thyroglobulin molecules

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27
Q

What is MIT?

A

Mono-iodotyrosine (MIT)

Has 1 iodine per tyrosine (T1)

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28
Q

What is DIT?

A

Di-iodotyrosine (DIT)
Has 2 iodines per tyrosine (T2)

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29
Q

DIT + DIT = ?

A

T4
Thyroxine

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30
Q

MIT + DIT = ?

A

T3
Triodothyronine

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31
Q

MIT + MIT = ?

A

Nothing, they do not couple.
T2 (DIT) cannot be synthesised this way.

32
Q

What are the stages of thyroid hormone synthesis?

A

(1)
Iodide (I-) trapping. Actively transported into follicles from blood.
(2)
Synthesis of TBG. TBG = Thyroxine-Binding Globulin
(3)
Oxidation of iodide to iodine (I2) It is initiated by thyroid peroxidase
(4)
Iodination of tyrosine. Iodine (I2) is incorporated into tyrosine residues
(5)
Coupling of MIT and DIT molecules to form T3 and T4
(6)
Pinocytosis and digestion of colloid. Lysosomal enzymes digest iodinated thyroglobulin
(7)
Secretion of thyroid hormones. T3 and T4 diffuse through plasma membrane into blood

33
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)

34
Q

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

A

T3 = 10%
T4 = 90%

35
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

36
Q

What happens to most T4 in the target tissue?

A

Most is converted to T3 by removing one iodine

37
Q

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

A

Liver and kidneys

38
Q

Where do T3 and T4 bind?

A

Intracellular thyroid hormone receptor

39
Q

Are thyroid hormones hydro/ lipophilic?

A

Lipophilic

Hence their need for binding to TBG in the blood

40
Q

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

A

(1) TBG: Thyroid-binding globulin
(2) Albumin

41
Q

What are the effects of thyroid hormone?

A

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

42
Q

How does thyroid hormone affect metabolic rate?

A

Increases basal metabolic rate

43
Q

How does thyroid hormone affect the CVS?

A

(1) Increases heart rate
(2) Increases force of heart contraction

44
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

45
Q

Name 2 examples of catecholamines

A

(1) Adrenaline
(2) Dopamine

46
Q

How does thyroid hormone affect growth and maturation?

A

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

47
Q

What is goitre? What causes it?

A

Hypertrophy of thyroid gland

Over-stimulation by TSH (Thyroid-stimulating hormone)

48
Q

How common is goitre?

A

Approximately 2% of the population

49
Q

What conditions are associated with goitre?

A

Either hypo/ hyperthyroidism

Often autoimmune

50
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

51
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

52
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

53
Q

How is hypothyroidism treated?

A

Lifelong levothyroxine therapy
Dose: 150mcg/ day

54
Q

How is levothyroxine administered? What advice applies?

A

Orally, as tablets

Take on an empty stomach - increases absorption

55
Q

What does levothyroxine imitate?

A

Natural T4

56
Q

What exception to treatment with levothyroxine is there?

A

Chronic dietary iodine deficiency

Treated with supplementary iodine in diet

57
Q

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

A

Dosing is not critical

T4 has a long half-life

58
Q

When is T3 (liothyronine) recommended?

A

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

59
Q

What is a primary cause of hypo/ hyperthyroidism?

A

Failure of the thyroid gland directly

60
Q

What is a secondary cause of hypo/ hyperthyroidism?

A

Failure of anterior pituitary gland

61
Q

What is a tertiary cause of hypo/ hyperthyroidism?

A

Failure of the hypothalamus

62
Q

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

A

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

63
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

64
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

65
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

66
Q

Is hyperthyroidism common?

A

Yes

Affects approx. 2% of women

67
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

68
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

69
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

70
Q

What are the effects of Graves’ disease?

A

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

71
Q

What are the treatment options for hyperthyroidism?

A

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

72
Q

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

A

Blocks the thyroid peroxidase enzyme

Prevents iodination of thyroglobulin

73
Q

What is first line treatment for hyperthyroidism?

A

Carbimazole

Propylthiouracil is given if 1st line not tolerated

74
Q

What are complications of hyperthyroidism treatment?

A

Often results in thyroid hypertrophy (goitre)

75
Q

When are drugs normally used in hyperthyroidism?

A

Prior to surgical resection (thyroidectomy)

76
Q

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

(2) How is it treated?

A

(1) Rash

(2) Antihistamine + switch to propylthiouracil

77
Q

What is an uncommon side-effect of carbimazole?

A

Suppression in bone marrow

Presents as sore throat, mouth ulcers, and fever

PM3B (33 decks)

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