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Semester 2 - MEH > 21. The Thyroid gland > Flashcards

21. The Thyroid gland Flashcards

1
Q

Where is the thyroid gland located?

A
  • Lies against and around front larynx and trachea
  • Below thyroid cartilage (Adam’s apple)
  • Isthmus extends from 2 nd to 3rd rings of the trachea
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2
Q

What are the 2 lobes of the thyroid gland joined by?

A

isthmus

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3
Q

When is the thyroid gland visible/palpable?

A

When enlarged ie goitre

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4
Q

Which two nerves lie close to gland? Functions of these nerves?

A

Recurrent laryngeal
External branch of superior laryngeal

Supply layrnx and invloved in speech

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5
Q

Which structures in neck are at risk during thyroid surgery?

A

2 nerves - recurrent laryngeal, external branch of superior laryngeal

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6
Q

Which 3 arteries and veins supply and drain thyroid?

A

superior, middle and inferior thyroid arteries and veins

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7
Q

Describe the development of the thyroid gland.

A

• At ~3-4 weeks gestation, thyroid gland appears as an epithelial proliferation in floor of pharynx at base of the
tongue and then takes several weeks to migrate to final position.
• First descends as diverticulum through thyroglossal duct and migrates downwards passing in front of hyoid
bone.
• During migration remains connected to tongue by thyroglossal duct which subsequently degenerates
• Detached thyroid then continues to its final position over following two weeks.

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8
Q

What endocrine gland is the first to develop?

A

Thyroid gland

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9
Q

Describe the shape of the thyroid glands

A

• The gland has a butterfly shape with two lateral lobes joined by a central isthmus.

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10
Q

What are the two major cell types found in the thyroid gland?

A

follicular cells and parafollicular (C-cells)

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11
Q

What are the cells that produce thyroid hormone called?

A

follicular cells.

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12
Q

How are follicular cells arranged?

A

In spheres called thyroid follicles separated by connective tissue

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13
Q

What are thyroid follicles filled with?

A

Colloid, a store of thyroglobulin

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14
Q

What are parafollicular cells?

A

Cells found between thyroid follicles which secrete calcitonin. ( The parafollicular cells are found in the connective tissue. )
- independent of follicular cells

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15
Q

Describe thyroid follicles

A

The follicles are spherical and are lined with epithelial (follicular) cells surrounding a central space (lumen) containing colloid which is rich in the protein thyroglobulin.

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16
Q

Which 3 hormones are produced in the thyroid and by what cells?

A

thyroxine (T4) and triiodothyronine (T3)- produced in follicular cells
Calcitonin - produced in parafollicular cells

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17
Q

What type of hormone is calcitonin? Function?

A

Pp hormone involved In calcium metabolism

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18
Q

Describe the chemical structure of the thyroid hormones

A

Thyroid hormones are made up of 2 tyrosines linked together with iodine at 3 or 4 positions in the aromatic rings.

T3 is made up of of 1 monoiodotyrosine (MIT) and a diiodotyrosine (DIT).

T4 is made up of 2 DITs

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19
Q

Describe the synthesis of thyroid hormones

A

The basic steps in the synthesis of T3 & T4 in the thyroid follicles are:
• Transport of iodide into the epithelial cells against a concentration gradient.
• Synthesis of a tyrosine rich protein (thyroglobulin) in the epithelial cells.
• Secretion (exocytosis) of thyroglobulin into the lumen of the follicle
• Oxidation of iodide to produce an iodinating species.
• Iodination of the side chains of tyrosine residues in thyroglobulin to form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine).
• Coupling of DIT with MIT or DIT to form T3 & T4 respectively within the thyroglobulin.

Iodide oxidation
Iodination
Coupling

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20
Q

Which does the thyroid gland produce more of - T3 or T4?

A

T4 bcs produced in ratio of T3:T4 = 1:10

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21
Q

What molecule are the thyroid hormones formed on?

A

Thyroglobulin

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22
Q

What is the key enzyme in thyroid hormone synthesis?

A 
Thyroid Peroxidase (TPO)
- membrane bound enzyme
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23
Q

What are the functions of TPO?

A

1) Oxidation of Iodide to Iodine
2) Addition of Iodine to tyrosine acceptor residues on the protein throglobulin
3) Coupling of MIT or DIT to generate thyroid hormones within the thyroglobulin protein

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24
Q

What does oxidation of iodide require?

A

Requires the presence of H2O2

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25
Q

How are thyroid hormones T3+4 secreted?

A

Thyroglobulin is taken into the epithelial cells from the lumen of the follicles by the process of endocytosis. The vesicles containing the thyroglobulin proteins with bind to lysosomes containing enzymes.Here proteolytic cleavage of the thyroglobulin occurs to release T3 & T4 and these diffuse from the epithelial cells into the circulation.

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26
Q

How are thyroid hormones T3+4 stored?

A

T3 & T4 are stored extracellularly in the lumen of the follicles as part of the thyroglobulin molecules. Quite a lot stored.

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27
Q

How is dietary iodine absorbed?

A

Reduced to iodide

- principally in the small intestine

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28
Q

What are the only molecules in the body that contain iodine?

A

Thyroid hormones and precursors

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29
Q

How is iodide taken up from the blood?

A

Iodide (I-), is taken up fromnblood by thyroid epithelial
cells, which have a sodiumiodide symporter or “iodine
trap”

Once in the thyroid cells the iodide will be converted back to iodine by thyroid peroxidase.

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30
Q

What form is the majority of the thyroid hormone released?

A

90% of thyroid hormone secreted is T4

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31
Q

How much T4 is converted into T3 and where?

A
  • Most T4 is converted to T3 in the liver & Kidneys

* 80% of circulating T3 is derived from T4

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32
Q

How much greater is T3 activity than T4?

A

4 times greater

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33
Q

How is T4 converted to T3?

A

By removal of the 5′-iodide

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34
Q

What is reverse T3 and how is it produced?

A

Removal of the 3′-iodide produces inactive reverse T3 (rT3). rT3 can bind to thyroid hormone receptors without stimulating them, but it blocks the effect of T3

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35
Q

How are thyroid hormones transported in the blood?

A

Bound to the protein thyroxine-binding globulin

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36
Q

How are levels of thyroid hormones regulated?

A

via Negative feedback

  • TSH feedbacks to hypothalamus
  • thyroid hormone feedbacks to anterior pituitary and hypothalamus
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37
Q

What are the effects of TSH?

A
  • stimulates all aspects of the synthesis and secretion of T3 & T4
  • trophic effects on the gland that result in increased vascularity, increase in size and number of the follicle cells (can cause goitre that may or may not be overactive)
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38
Q

What type of hormone is TSH and what is its structure?

A
  • Glycoprotein hormone composed of 2 noncovalently bound subunits (a and b).
  • The a subunit is also present in FSH and LH.
  • b subunit provides unique biological activity.
39
Q

What is the receptor for TSH?

A

GPCR

  • Gαs coupled
  • Gαq coupled at higher concentrations
  • produce the same effects
40
Q

How is activity of the thyroid gland controlled?

A

The synthesis and secretion of T3 & T4 are under the control of the hypothalamus and anterior pituitary gland.

The hypothalamic factor is Thyrotropin-Releasing Hormone (TRH). This is a tri-peptide released from cells in the dorsomedial nucleus of the hypothalamus.

TRH travels in the hypothalamic/pituitary portal system to stimulate the secretion of Thyroid Stimulating Hormone (TSH) from the thyrotropes in the anterior pituitary.

TSH travels in the blood to affect the follicular cells of the thyroid gland.

41
Q

What factors influence the release of TRH from the hypothalamus?

A

Circulating levels of T3+4 (negative feedback)
Stress (increases release)
Temperature (fall in temp increases release)

42
Q

What rhythm is TSH released in?

A

Diurnal rhythm - low amplitude pulses with higher levels attained during the night and decreasing in the early morning.

43
Q

Which (T3 or T4) is more biologically active and why?

A

Only a small amount (<1%) of T3 & T4 is free in solution and it is this free hormone that is biologically active. T3 has a slightly lower affinity for the transport proteins than T4 and hence a greater percentage is free and its half-life in the circulation is therefore shorter
(2 days compared to 8 days for T4).

44
Q

What is the effect of oestrogen on free thyroid hormone?

A

Oestrogens increase the synthesis of TBG during pregnancy and this produces a fall in the amount of T3 & T4 in the circulation

45
Q

Oestrogens increase the synthesis of TBG during pregnancy and this produces a fall in the amount of T3 & T4 in the circulation

A

Increased oestrogen production leads to increases production of TBG. produces a fall in the amount of T3 & T4 in the circulation as more is bound. The fall in free T3 &T4 removes the inhibitory feedback on the pituitary and hypothalamus. More TRH and TSH are produced and the thyroid gland secretes more T3 & T4. As a result the amount of free T3 & T4 returns to normal but the total amount in the blood is increased

46
Q

What are the 2 general interconnected effects of thyroid hormone?

A
  • Effects on cellular differentiation and development

* Effects on metabolic pathways

47
Q

What does TSH stimulate?

A
  • Iodide uptake
  • Iodide oxidation
  • Thyroglobulin synthesis
  • Thyroglobulin iodination
  • Colloid pinocytosis into cell
  • Proteolysis ofthyroglobulin
  • Cell metabolism & Growth
48
Q

What are the 3 general actions of thyroid hormone?

A
  • increase in basal metabolic rate and heat production
  • stimulation of metabolic pathways
  • sympathomimetic effects
49
Q

How does thyroid hormone increase BMR and heat production?

A
  • Increasing the number and size of mitochondria

* Stimulating the synthesis of enzymes in the respiratory chain

50
Q

In which tissues does thyroid hormone not effect metabolic rate?

A

brain, spleen and testis

51
Q

Which metabolic pathways does thyroid hormone stimulate?

A

Catabolic pathways are generally stimulated more than anabolic.
• Lipid metabolism: Stimulates lipolysis and b-oxidation of fatty acids
• Carbohydrate metabolism: Stimulate insulin-dependent entry of glucose into cells and increase gluconeogenesis and glycogenolysis

52
Q

What is the sympathomimetic effects of thyroid hormone?

A

Increases target cell response to catecholamines by increasing receptor number on target cells

53
Q

What are the specific effects of thyroid hormone on the CVS?

A

Increases heart’s responsiveness to catecholamines (increase in noradrenaline receptors)
↑ cardiac output (↑ in heart rate and ↑ in force of contraction)
↑ Peripheral vasodilation to carry extra heat to body surface

54
Q

What are the specific effects of thyroid hormone on the nervous system?

A

Essential for both development and adult function

↑ Myelination of nerves & development of neurons.

55
Q

What metabolic effects do T3+4 have?

A
  • ↑ metabolic rate
  • Stimulate glucose uptake + metabolism
  • Stimulate mobilisation + oxidation of FAs
  • Stimulate protein metabolism
  • Catabolic (↑BMR, heat production, ↑O2 consumption)
56
Q

How do T3+4 effect growth and development of bones and heart?

A

Bone mineralisation + ↑ synthesis of heart muscle protein

57
Q

How do T3+4 effect hormones and NTs?

A

Stimulate hormone and NT receptor synthesis in heart muscle + GI tract. This leads to increased responsiveness of these tissues to regulatory factors, so:

heart: Tachycardia
↑ motility of GI tract

58
Q

What does it mean that T3+4 play a “permissive role” in the actions of FSH+LH hormones?

A

Their presence is required in order for FSH+LH to exert their full effects.

59
Q

How are T3+4 involved in reproduction?

A

Ovulation fails to occur in absence of thyroid hormones -“permissive role” in actions of FSH+LH.

60
Q

What family of receptors does the thyroid hormone receptor belong to?

A

Nuclear receptors

61
Q

What is the normal state of the thyroid receptor?

A
  • Function as hormone-activated transcription factors
  • Act by modulating gene expression
  • Thyroid hormone receptors bind DNA in the absence of hormone, usually leading to transcriptional repression
62
Q

What is the effect of thyroid hormone binding to its receptor?

A

Hormone binding is associated with a conformational change in the receptor that causes it to function as a transcriptional activator - relieves repression of gene transcription

63
Q

Give examples of thyroid hormone activated genes.

A
  • Phosphoenolpyruvate carboxy kinase (PEPCK)
  • Ca2+ ATPase
  • Na+, K+ ATPase
  • Cytochrome oxidase
  • 6-phosphogluconate dehydrogenase (pentose phosphate pathway)
64
Q

What are the normal plasma concentration of thyroid hormones and TSH?

A 
Free T4 (0.7 - 2.1 ng/dl) 10 - 25 pM
Free T3 (0.2 - 0.5 ng/dl) 3 - 8 pM
TSH (0.3 - 4.0 mIU/L) 1 - 15 pM
65
Q

Describe the mechanism of action of T3+4

A
  • Thyroid hormone is Lipid soluble and enters cell through thyroid hormone transporters
  • Thyroid hormone receptor is prebound to specific DNA sequences on DNA called a hormone response elements (HRE) in promoter region of thyroid hormone regulated genes
  • Thyroid hormone enters nucleus and binds to thyroid hormone receptor on DNA causing conformational change. Binding relieves repression of gene transcription and the gene is now expressed
  • Interaction of the hormone-receptor complex with DNA (nuclear or mitochondrial) increases the rate of transcription of specific genes that are then translated into protein.
66
Q

Where are the receptors for T3+4 found in target tissues? Which hormone do they have a higher affinity for?

A

Nucleus + mito.

T3

67
Q

Define goitre.

A

Enlargement of the thyroid gland

68
Q

What are the causes of hypothyroidism?

A
  • Failure of thyroid gland
  • TSH or TRH deficiency
  • Inadequate dietary supply of iodine
  • Radioactive iodine
  • Autoimmunity
  • Post surgery
  • Congenital
  • Anti-thyroid drugs
69
Q

When does a goitre occur?

A

• May accompany either hypo- or hyperthyroidism
(but not necessarily present in either)
• Develops when the thyroid gland is overstimulated

70
Q

What are the general symptoms of hypothyroidism?

A
  • Obesity • Lethargy
  • Intolerance to cold • Bradycardia
  • Dry skin • Alopecia • Hoarse voice
  • Constipation • Slow reflexes
71
Q

How are the levels of T3, T4 and TSH in hypothyroidism?

A
  • Low T3
  • Low T4
  • Elevated TSH
72
Q

What does hypothryoidism in children cause?

A

Cretinism

73
Q

What is cretinism?

A

Congenital hypothyroidism resulting in severely stunted physical and mental growth

74
Q

Why does congenital hypothyroidism lead to retardation?

A

Thyroid hormone required for development of the nervous system

75
Q

Describe 3 specific effects the thyroid hormone has on the central nervous system (CNS)

A

The CNS is very sensitive to thyroid hormones particularly during development.

They’re needed for the development
of the cellular processes of nerve cells, hyperplasia of cortical neurons and myelination of nerve fibres.

76
Q

What are the symptoms associated with cretinism?

A
  • Dwarfed stature
  • Mental deficiency
  • Poor bone dev
  • Slow pulse
  • Muscle weakness
  • GI disturbances
77
Q

What does hypothryoidism in adults cause?

A

myxedema

78
Q

What is myxedema and what are the clinical presentations?

A 
Severe hypothyroidism
•Thick puffy skin
•Muscle weakness
•Slow speech
•Mental deterioration
•Intolerance to cold
79
Q

What is Hashimoto’s disease?

A

Autoimmune disease resulting in destruction of thyroid follicles. Leads to hypothyroidism
• Most common disease of the thyroid gland

80
Q

How are plasma concentrations of thyroid hormone and TSH affected in Hashimoto’s?

A
  • Low T3
  • Low T4
  • Elevated TSH
81
Q

What is the treatment for Hashimoto’s disease?

A

• Oral Thyroid hormone.
• T4 used since longer half-life
• Normally ~50-200 mg/day in
single dose.

82
Q

Is a goitre present in hashimoto’s?

A

Goitre may or may not be present

83
Q

What are the general symptoms of hyperthyroidism?

A 
• Weight loss
• Irritability
• Heat intolerance, sweating warm vasodilated hands
• Tachycardia (noticeable heart beat) often irregular
• Fatigue, weakness
• Increased bowel movements
- increased appetite
• Possible tremor of outstretched hands
• Hyper-reflexive
• Breathlessness
• Loss of libido
• Sweating and tremor
84
Q

Which two symptoms are present in some but not all cases of Hashimoto’s?

A
  • Goitre

* Bulging eyes

85
Q

What is Grave’s disease and what causes it?

A

Autoimmune disease resulting in hyperthyroidism
Caused by production of thyroid stimulating immunoglobulin (TSI)

• TSI continuously stimulates thyroid hormone secretion outside normal negative feedback control

86
Q

How are plasma concentrations of thyroid hormone and TSH affected in Grave’s?

A

Increased T3
Increased T4
Very low TSH

87
Q

What are the symptoms of Grave’s?

A 
• Increase In BMR
• Excessive sweating
• Decrease in body weight
• Muscle weakness
• Heart palpitations
• Bulging eyes
(not in every case)
88
Q

What is thyroid scintigraphy and what substances are usually used?

A

Radioactive marker identifies functional thyroid tissue administration of 99m-technetium or 123-Iodine isotope

89
Q

Why is technietium used in thyroid scintigraphy?

A
  • Biological half-life of ~1 day

* Radiation exposure therefore low

90
Q

Give an examples of antithyroid drug.

A

Carbimazole

- is a pro-drug and is converted to methimazole in body

91
Q

What are antithyroid drugs used for?

A

• Used to treat overactive thyroid (hyperthyroidism) e.g.
Graves’ disease
• Block formation of thyroid hormone

92
Q

How does carbimazole worK?

A

Prevents thyroid peroxidase from coupling and iodinating tyrosines on thyroglobulin

93
Q

How many iodines in thyroxine?

A

T4 so 4 iodines

94
Q

How many iodines in triiodothyronine?

A

T3 so 3 iodines

Semester 2 - MEH (23 decks)

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