(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
What type of iodine is included in the tyrosine residues?
Free iodine
26
Where are tyrosine residues found?
Thyroglobulin molecules
27
What is MIT?
Mono-iodotyrosine (MIT) Has 1 iodine per tyrosine (T1)
28
What is DIT?
Di-iodotyrosine (DIT) Has 2 iodines per tyrosine (T2)
29
DIT + DIT = ?
T4 Thyroxine
30
MIT + DIT = ?
T3 Triodothyronine
31
MIT + MIT = ?
Nothing, they do not couple. T2 (DIT) cannot be synthesised this way.
32
What are the stages of thyroid hormone synthesis?
(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
What does TBG do? Why?
(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
What percentages of overall secreted thyroid hormone do T3 and T4 comprise?
T3 = 10% T4 = 90%
35
Which thyroid hormone is more potent? Why?
T3 is about 4x more potent T3 binds to the intracellular thyroid hormone receptor with greater affinity
36
What happens to most T4 in the target tissue?
Most is converted to T3 by removing one iodine
37
Which organs are particularly important for activating the conversion of T4 to T3?
Liver and kidneys
38
Where do T3 and T4 bind?
Intracellular thyroid hormone receptor
39
Are thyroid hormones hydro/ lipophilic?
Lipophilic Hence their need for binding to TBG in the blood
40
What molecule can thyroid hormones bind to in the blood to prevent urinary excretion?
(1) TBG: Thyroid-binding globulin (2) Albumin
41
What are the effects of thyroid hormone?
(1) Metabolic Rate (2) Cardiovascular system (3) Nervous system (4) Growth and maturation
42
How does thyroid hormone affect metabolic rate?
Increases basal metabolic rate
43
How does thyroid hormone affect the CVS?
(1) Increases heart rate (2) Increases force of heart contraction
44
How does thyroid hormone affect the NS?
(1) Increases activity of sympathetic NS (2) Increases sensitivity to catecholamines - such as adrenaline or dopamine
45
Name 2 examples of catecholamines
(1) Adrenaline (2) Dopamine
46
How does thyroid hormone affect growth and maturation?
(1) Embyro development (2) CNS development (3) Linear growth - increases affect of growth hormone
47
What is goitre? What causes it?
Hypertrophy of thyroid gland Over-stimulation by TSH (Thyroid-stimulating hormone)
48
How common is goitre?
Approximately 2% of the population
49
What conditions are associated with goitre?
Either hypo/ hyperthyroidism Often autoimmune
50
What are the common symptoms/ features of hypothyroidism?
(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
What symptoms/ features are commonly present in children with hypothyroidism?
(1) Cretinism (2) Obesity (3) Stunted growth (4) Mental retardation - irreversible foetal brain damage
52
How is hypothyroidism detected early in children?
Routine elevated TSH checks for neonates High TSH indicates low T3/T4 - limited negative feedback on hypothalamus and pituitary
53
How is hypothyroidism treated?
Lifelong levothyroxine therapy Dose: 150mcg/ day
54
How is levothyroxine administered? What advice applies?
Orally, as tablets Take on an empty stomach - increases absorption
55
What does levothyroxine imitate?
Natural T4
56
What exception to treatment with levothyroxine is there?
Chronic dietary iodine deficiency Treated with supplementary iodine in diet
57
Why is T4 (levothyroxine) chosen over T3 in the UK?
Dosing is not critical T4 has a long half-life
58
When is T3 (liothyronine) recommended?
When faster-acting is required - such as myxedema coma/ preparation for ablation with radioactive iodine
59
What is a primary cause of hypo/ hyperthyroidism?
Failure of the thyroid gland directly
60
What is a secondary cause of hypo/ hyperthyroidism?
Failure of anterior pituitary gland
61
What is a tertiary cause of hypo/ hyperthyroidism?
Failure of the hypothalamus
62
What are the effects of failure of the thyroid gland in hypothyroidism?
(1) Low T3/ T4 (2) High TSH (3) Goitre
63
What are the effects of anterior pituitary failure in hypothyroidism?
(1) Low T3/ T4 (2) Low TSH (and TRH) (3) No goitre Has the same symptoms as hypothalamic (tertiary) failure
64
What are the effects of hypothalamic failure in hypothyroidism?
(1) Low T3/ T4 (2) Low TSH (and TRH) (3) No goitre Has the same symptoms as anterior pituitary (secondary) failure VERY RARE
65
What are 3 different types of primary thyroid failure in hypothyroidism?
(1) Thyroid failure (2) Autoimmune damage to gland (Hashimoto's thyroiditis) (3) Chronic lack of dietary iodine
66
Is hyperthyroidism common?
Yes Affects approx. 2% of women
67
What are common symptoms/ features of hyperthyroidism?
(1) Weight loss (2) Nervousness (3) Heat intolerance (4) High cardiac output (5) Hand tremors (6) Eyeball protrusion - exophthalmos
68
(1) What is a primary cause of hyperthyroidism? (2) What are its effects?
(1) Hypersecreting tumour (2) - High T3/ T4 - Low TSH - No goitre
69
(1) What is a secondary cause of hyperthyroidism? (2) What are its effects?
(1) Excess anterior pituitary/ hypothalamic secretion (2) - High TRH/ TSH - High T3 and T4 - Goitre
70
What are the effects of Graves' disease?
(1) High T3/ T4 (2) Low TSH (3) Goitre
71
What are the treatment options for hyperthyroidism?
Anti-thyroid drugs to interfere with thyroid hormone synthesis/ surgical resection/ thyroid ablation using iodine
72
What is the mechanism of action of an anti-thyroid drug?
Blocks the thyroid peroxidase enzyme Prevents iodination of thyroglobulin
73
What is first line treatment for hyperthyroidism?
Carbimazole Propylthiouracil is given if 1st line not tolerated
74
What are complications of hyperthyroidism treatment?
Often results in thyroid hypertrophy (goitre)
75
When are drugs normally used in hyperthyroidism?
Prior to surgical resection (thyroidectomy)
76
(1) What is a common side-effect of carbimazole? (2) How is it treated?
(1) Rash (2) Antihistamine + switch to propylthiouracil
77
What is an uncommon side-effect of carbimazole?
Suppression in bone marrow Presents as sore throat, mouth ulcers, and fever