11.1 The Thyroid Gland Flashcards
1
Q
Where is the thyroid gland located?
A
- Lies against and around front larynx and trachea, anterior to the cricoid cartilage. Roughly at the level of the C7 vertebrae
- Below thyroid cartilage (Adam’s apple)
- Isthmus extends from 2nd to 3rd rings of the trachea
2
Q
Describe the shape of the thyroid gland?
A
Bow tie shape
2 lobes joined by isthmus
3
Q
What is the cricoid cartilage?
A
The first notch beneath the thyroid cartilage
4
Q
What is the first endocrine gland to develop
A
Thyroid
5
Q
Where is the embryological origin 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 the takes several weeks to
migrate to final position.
6
Q
What is the thyroid diverticulum?
A
The embryological origin of the thyroid gland. This epithelial proliferation descends through thyroglossal duct, migrating downwards passing in front of the hyoid bone
7
Q
What is the hyoid bone?
A
A u shaped bone that supports the tongue
8
Q
What is the thyroglossal duct?
A
The remaining connection between the thyroid and the tongue. Does subsequently degenerate after migration.
9
Q
What do parafollicular cells secrete?
A
Calcitonin - used in calcium homeostasis
10
Q
Where are follicular cells located?
A
In the thyroid tissue. Arranged in spheres called thyroid follicules.
11
Q
What are the spherical structures in the thyroid tissue?
A
Thyroid follicles
12
Q
What are the follicle cells in the thyroid filled with?
A
Colloid, a deposit of thyroglobulin.
13
Q
Where is thyroglobulin stored?
A
Stored extracellularly inside follicles as colloid.
14
Q
What are thyroid hormones made of ?
A
Thyroglobulin.
15
Q
What are chief cells?
A
Also known as parathyroid principal cells, chief cells are in the parathyroid glands.
16
Q
What cells produce parathyroid hormone?
A
Chief cells.
17
Q
What cells produce thyroid hormone?
A
Thyroid follicular cells.
18
Q
What cells produce calcitonin?
A
Thyroid parafollicular cells
19
Q
Describe the structure of thyroid hormones?
A
2 tyrosine molecules linked together with iodine at three or four positions on the aromatic rings.
20
Q
How is the thyroid hormone T3 produced?
A
T3 = triiodothyronine
Made from monoiodotyrosine linking with diiodotyrosine
21
Q
How is the thyroid hormone T4 produced?
A
T4 = tetraiodothyronine (thyroxine)
Made from linking diiodotyrosine and diiodotyrosine together
22
Q
What is the purpose of thyroglobulin?
A
To act as a scaffold on which thyroid hormones are formed.
23
Q
Describe for thyroid hormones are formed
A
- Tyrosine residues bind to thyroglobulin.
- Iodisation of tyrosine residues on thyroglobulin.
- Two iodinated tyrosine residues on the thyroglobulin link together and are then coupled.
- Thyroglobulin protein undergoes degeneration, releasing thyroid hormones T3 and T4
24
Q
What is the function of thyroid peroxidase?
A
Membrane bound enzyme that regulates 3 separate reactions involving iodine
25
What reactions require thyroid peroxidase?
1. Oxidation of iodide to iodine (H2O2 required)
2. Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin in the colloid of thyroid follicles.
3. Coupling of monoiodotyrosine and diiodotyrosine to generate thyroid hormones within the thyroglobulin protein.
26
How is iodine absorbed into the body?
Dietary iodine must be reduced to iodide before absorption into the small intestine.
27
What channel protein moves iodine into thyroid epithelial cells from blood stream?
Sodium iodide symporter.
28
What molecules in the body contain iodine?
Thyroid hormone and precursors.
29
What are common sources of iodine.
```
Dairy products
Grains
Meat
Vegetable
Eggs
Iodised salt.
```
30
Describe how Thyroid hormones are synthesised and released?
1. Amino acids and iodide (alongside 2Na via the symporter) are absorbed across the basal surface of the thyroid follicular cells from the interstitial fluid.
2. Tyrosine amino acids and iodide are transported into the colloid. Iodide is oxidative to iodine.
3. Within the extracellular colloid space the thyroglobulin protein acts as a scaffold on which thyroid hormones are formed from tyrosine residues and iodine.
4. Pinocytosis of some of the colloid ( including thyroglobulin with thyroid hormones T3 and T4 still attached ) into the thyroid follicle cell.
5. Lysosome within the thyroid follicle cells pinches off some of the absorbed colloid.
6. Enzymes within the lysosome degrade the thyroglobulin protein, releasing the thyroid hormones.
7. Coupled iodotyrosine molecules form thyroid hormones and are released from the thyroid follicle cells into the interstitial fluid. Uncoupled iodotyrosine molecules stay within the thyroid follicle cells, are deiodinated by deiodinase, and reused.
31
Which thyroid hormone is mostly secreted by the thyroid?
T4. Most (90%) of the thyroid hormone secreted is T4.
32
Which thyroid hormone is most biologically active?
T3.
| Biological activity of T3 is four times that of T4.
33
How is T3 predominantly produced?
Predominantly (80%) produced in the liver and kidneys by converting T4 into T3. Smaller amount (20%) produced and secreted by the thyroid follicular cells.
34
How are T3 and T4 transported within the blood?
Bound to the protein thyroxine-binding globulin. When bound the hormones are inactive. Small amount is also free within the blood.
35
How is secretion of the thyroid hormones regulated?
Regulated via negative feedback loops from TSH and thyroid hormone concentrations.
36
What hormones stimulate thyroid hormone release?
1. Thyrotropin releasing hormone / TRH ( from hypothalamus to act on the anterior pituitary )
2. Thyroid stimulating hormone / TSH ( from the anterior pituitary to act on the thyroid gland)
37
How are TSH levels in hyperthyroidism?
Thyroid hormones act vis negative feedback loop to inhibit secretion of TSH from the anterior pituitary hence the TSH levels are very low.
38
What 2 effects do thyroid hormones have of body cells?
1. Effects on cellular differentiation and development (growth)
2. Effects on metabolic pathways
39
Describe the structure of thyroid stimulating hormone
TSH is a glycoprotein hormone composed of 2 non-covalently bound subunits ( alpha and beta)
Beta subunit provided unique biological activity.
40
What does TSH stimulate?
* Iodide uptake
* Iodide oxidation
* Thyroglobulin synthesis
* Thyroglobulin iodination
* Colloid pinocytosis by thyroid follicle cells
* Proteolysis of thyroglobulin
* Cell metabolism & Growth
Stimulates many of the reactions in the production of thyroid hormones and triggers thyroid hormone release.
41
What second messenger pathways does TSH activate within thyroid follicle cells?
TSH activates TSH receptor.
TSH receptor can couple to either a G-alpha-s protein or a G-alpha-q protein.
G-alpha-s protein = stimulates adenylyl cyclase -> cAMP -> Protein kinase A
G-alpha-q protein = stimulates phospholipase C -> DAG and IP3 ->IP3 receptor trigger calcium release, DAG activates PKC
Both second messenger pathways result in stimulation of thyroid hormones synthesis and release.
42
What are the 3 general actions of thyroid hormone?
1. Increase Basal metabolic rate and heat production
2. Stimulation of metabolic pathways
3. Sympathomimetic effects
43
What tissues do thyroid hormones stimulate increase in basal metabolic rate?
All tissues apart form brain, spleen and testis
44
How do thyroid hormones increase basal metabolic rate of tissues?
* Increasing the number and size of mitochondria
| * Stimulating the synthesis of enzymes in the respiratory chain (oxidative phosphorylation)
45
Which metabolic pathways are stimulated by thyroid hormones?
Catabolic pathways
* 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
46
What are the sympathomimetic effects of thyroid hormones in tissues?
Thyroid hormones increase the target cells response to catecholamines by increasing receptor number on target cells.
Increase expression of adrenergic receptors, so that cells are more sensitive to noradrenalin and adrenalin.
47
What affect do thyroid hormones have on the cardiovascular system?
- increases the hearts responsiveness to catecholamines by enhancement of b2 adronergic receptors in vascular walls ( sympathetic autonomic system )
- increased cardiac output ( due to increased heart rate and increased force of contraction)
- increased peripheral vasodilation, extra heat carried to the body surface.
48
How do thyroid hormones affect the nervous system?
Essential for development
| - increases myelination of the nerves and development of the neurons.
49
What is cretinism?
condition characterized by physical deformity and learning difficulties that is caused by congenital thyroid deficiency (hypothyroidism )
50
Describe the function of thyroid hormone receptors
- Nuclear intracellular receptor
- function as hormone activated transcription factors
- act by modulating gene expression
- In the absence of thyroid hormone, receptors are bound to the DNA leading to transcriptional repression.
- thyroid hormone binding leads to conformational change in the receptor that causes it to function as a transcriptional activator.
51
How does thyroid hormone enter cells?
Thyroid hormones are lipid soluble and pass freely into cells via thyroid hormone transporters.
52
What is the hormone response element (HRE) of DNA?
A DNA sequence that the thyroid hormone receptor is pre bound to. The hormone response elements are located in the promoter region of the thyroid hormone regulated genes.
53
What occurs when thyroid hormone binds to the thyroid hormone receptor on the hormone response element?
Binding causes conformational change and relieves the repression of gene transcription. Gene is now expressed.
54
Give examples of thyroid hormone activated genes.
- Phosphoenolpyruvate carboxy kinase (PEPCK)
- Ca2+ ATPase
- Na+, K+ ATPase
- Cytochrome oxidase
- 6-phosphogluconate dehydrogenase.
55
What is the SI unit for thyroid hormones?
Picomolar (pM)
56
What could cause variation in thyroid hormone within plasma other than thyroid disease?
Methodological factors
Albumin changes
Dilution effects
57
What is a goitre?
A visible enlargement of the thyroid gland
58
When is a goitre seen?
When the thyroid is overstimulated.
May accompany hypo or hyper thyroidism (or neither)
Lack of dietary iron regularly causes goitre
59
What is hypothyroidism?
Too little production of thyroid hormones.
60
What are the main causes of hypothyroidism?
- Failure of thyroid gland
- TSH or TRH deficiency
- inadequate dietary supply of iodine
- Radioactive Iodine
- Autoimmunity
- Post surgery
- Congenital
- anti-thyroid drugs
61
What are the general symptoms of hypothyroidism?
```
Obesity
Lethargy
Intolerance to the cold
Bradycardia
Dry skin
Alopecia
Hoarse voice
Constipation
Slow reflexes
```
62
What are the biochemical signs of hypothyroidism?
Low T3
Low T4
Elevated TSH
63
What is cretinism?
Cretinism is a condition caused by hypothyroidism in children.
64
What are the signs and symptoms of cretinism?
- dwarfed stature
- mental deficiency
- poor bone development
- slow pulse
- muscle weakness
- GI disturbances
65
What is myxedema?
Myxedema is a general term for hypothyroidism in adults
66
What are the signs and symptoms of myxedema?
- thick puffy skin
- muscle weakness
- slow speech
- mental deterioration
- intolerance to the cold
67
What is Hashimotos disease?
Hashimotos disease is an autoimmune disease that results in the destruction of thyroid follicles and therefore hypothyroidism.
68
Which gender are more likely to suffer from hashimotos disease?
Women are 5 times more likely to suffer from hashimotos disease than men
69
Is a goitre present in a patient with hashimotos disease?
May be present, may not be.
70
What are the biochemical signs of hashimotos disease?
The same as hypothyroidism.
Low T3 and T4
Elevated TSH
71
How is Hashimotos disease treated?
Oral thyroid hormone
| T4 is used since it has a longer half life and is converted to T3
72
What are common causes of hyperthyroidism?
```
Autoimmune Graves’ disease
Toxic multinodular goitre
Solitary toxic adenoma
Excessive T4 therapy
Drugs (amiodarone)
Ectopic thyroid tissue
```
73
What are the general symptoms of a patient with hyperthyroidism?
```
• 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
```
74
What is Graves’ disease?
An autoimmune condition resulting in hyperthyroidism
75
What are the signs of hyperthyroidism?
Sometimes patients have goitre and bulging eyes. Caused by the production of thyroid stimulating immunoglobin
76
Why are T3 and T4 levels raised in Graves’ disease?
Increased production of thyroid stimulating immunoglobin stimulated thyroid hormone secretion outside normal negative feedback range.
77
What are the signs and symptoms of Graves’ disease?
```
increase in basal metabolic rate
Excessive sweating
Decrease in body weight
Muscle weakness
Heart palpitations
Bulging eyes
```
78
What is thyroid scintigraphy?
A form of medical imaging using a radioisotope. Isotope scanning of the thyroid using a gamma camera
79
What radioisotope is commonly used in thyroid scintigraphy?
Technetium-99m. Used as it has a short half life (1 day)
80
What is technetium-99m used for?
```
Used during imaging of:
Thyroid
Bone scan
Myocardial perfusion imaging
Brain
```
81
What are anti thyroid drugs used to treat?
Hyperthyroidism
| Graves’ disease
82
What do antithyroid drugs do?
Block formation of the thyroid hormones
83
What antithyroid drug is commonly used within the UK?
Carbimazole
84
Why is Carbimazole described as a pro-drug?
As Carbimazole is a biologically inactive compound which can be metabolized in the body to produce a drug. Carbimazole is converted into the active drug methimazole in the body.
85
What is the function of methimazole?
To prevent thyroid peroxidase from coupling and iodinating tyrosine on thyroglobulin.
86
Why must Carbimazole be taken for 2/3 months before seeing effects?
As we have big stores of thyroglobuliniin the colloid space within the follicular cells.
