Lecture 11: Thyroid hormones and thyroid disease Flashcards
1
Q
The thyroid gland is located immediately below the ____ on each side of and anterior to the ____.
A
A) Larynx
B) Trachea
2
Q
What three hormones does the thyroid gland produce
A
- Thyroxine (T4)
- Triiodothyronine (T3)
- Calcitonin
3
Q
Thyroid secretion is controlled primarily by _____ secreted by the ______.
A
A) Thyroid-stimulating hormone (TSH)
B) Anterior pituitary gland
4
Q
Thyroid disease is more common in which gender?
A
Women
Affect 5% women and 0.5% men in the population
5
Q
Which metabolically active hormones is secreted more by the thyroid gland
A) T3
B) T4
A
B) Thyroxine (T4)
93% = Thyroxine (T4)
7% = Triiodothyronine (T3)
6
Q
Which thyroid hormone is more potent?
A
Triiodothyronine is about four times as potent as thyroxine, but it is present in the blood in much smaller quantities and persists for a much shorter time compared with thyroxine.
7
Q
_____ is the essential component of the thyroid hormone synthesise
A
Iodine
8
Q
Describe the histology of the thyroid gland
A
- Composed of large numbers of closed follicles (100 to 300 micrometers in diameter) that are filled with a secretory substance called colloid and lined with cuboidal epithelial cells that secrete into the interior of the follicles.
- The major constituent of colloid is the large glycoprotein thyroglobulin, which contains the thyroid hormones.
- Once the secretion has entered the follicles, it must be absorbed back through the follicular epithelium into the blood before it can function in the body.
9
Q
Fill in the blanks
A
10
Q
The thyroid is divided into two lobes which are connected by ____.
A
an isthmus.
11
Q
Describe what happens to the follicular cells during the storage and secretion stage?
A
- When the follicular cells become stimulated they become columnar and the lumen is depleted of colloid
- When suppressed the cells become flat and colloid accumulates in the lumen
12
Q
Iodine is found in which foods
A
Found in seawater, fruit and vegetables
13
Q
What amount of iodine must be ingested per day
A
Require 150-300 µg daily
Requirement may vary depending on many factors such as breastfeeding
14
Q
Iodine deficiency mainly occurs in which geograpical location and what does this lead to ?
A
Mainly occurs in inland areas at high altitude
Leads to endemic goitre (enlargement of the thyroid gland)
15
Q
Oral iodine is reduced to _____ in the GI tract and absorbed
A
Iodide
16
Q
To prevent iodine deficiency, which food substance has had iodine supplementation added
A
Common table salt
17
Q
Describe how the follicular cells in the thyroid gland take up iodide
A
- Iodide is actively transported into follicular cells by the sodium iodide symporter (NIS) on the basolateral membrane against a chemical gradient.
- Co-transports one iodide ion along with two sodium ions across the basolateral (plasma) membrane into the cell.
- The energy for transporting iodide against a concentration gradient comes from the sodium-potassium ATPase, which pumps sodium out of the cell, thereby establishing a low intracellular sodium concentration and a gradient for facilitated diffusion of sodium into the cell.
18
Q
Define the term iodide trapping
A
In a normal thyroid gland, the iodide pump concentrates the iodide to about 30 times its concentration in the blood.
When the thyroid gland becomes maximally active, this concentration ratio can rise to as high as 250 times.
19
Q
Describe how the iodide is transported from the follicular cell into the colloid
A
- Iodide is transported out of the thyroid cells across the apical membrane into the follicle by a chloride-iodide ion counter-transporter molecule called pendrin.
- Pendrin released iodide into the colloid in vesicles
20
Q
Describe the Organification process involved in the development of thyroid hormone
A
- The thyroid epithelial cells also secrete into the follicle thyroglobulin that contains tyrosine
- Iodide ions is converted to an oxidized forn, iodine.
- Oxidation of iodide to iodine occurs in the vesicles
- The iodine binds directly with the tyrosine residues on thyroglobulin. The binding of the iodine to the tyrosine residue is called “organification”.
- Tyrosine is first iodized to monoiodotyrosine and then to diiodotyrosine.
21
Q
monoiodotyrosine + diiodotyrosine = forms which thyroid hormone?
A
Triiodothyronine (T3)
22
Q
diiodotyrosine + diiodotyrosine = forms which thyroid hormone?
A
Thyroxine (T4)
23
Q
Describe reverse T3
A
Small amounts of reverse T3 (RT3) are formed by coupling of diiodotyrosine with monoiodotyrosine, but RT3 does not appear to be of functional significance in humans.
24
Q
Describe how thyroxine and Triiodothyronine are released from the Thyroid Gland
A
- Most of the thyroglobulin is not released into the circulating blood; instead, thyroxine and triiodothyronine are cleaved from the thyroglobulin molecule, and then these free hormones are released.
- Droplet containing the thyroglobulin molecules with T3 and T4 enter the cell.
- Then lysosomes in the cell cytoplasm immediately fuse with these vesicles. Proteases hydrolyses the thyroglobulin molecules and release thyroxine and triiodothyronine in free form, which then diffuse through the base of the follicular cell into the surrounding capillaries.
- Thus, the thyroid hormones are released into the blood.
25
The oxidation of iodide to iodine is promoted by which enzyme?
Thyroid peroxidase
26
Iodine combines with tyrosine to form what molecule(s)
monoiodotyrosine and diiodotyrosine
27
T\_\_ is release in greatest quantity, and solely, by the thyroid gland
T4
28
T\_\_ is the most active thyroid hormone
Triiodothyronine (T3)
29
Almost all the _____ is eventually converted to ____ in the peripheral circulation
A) Thyroxine
B) Triiodothyronine
30
Why is it important that thyroxine is converted to triiodothyronine in the peripheral circulation
* Both are functionally important
* Regulates the amount of thyroid hormone each tissue is exposed to (as thyroid hormone has a widespread mechanism). Therefore, by controlling the level of T3, some tissues will see more than others.
31
Compare and contrast triiodothyronine (T3) and thyroxine (T4)?
* Functions of these two hormones are qualitatively the same
* Triiodothyronine (T3) about four times as potent as thyroxine (T4)
* Triiodothyronine (T3) persist for a shorter time compared to thyroxine (T4).
* Thyroxine (T4) is found in higher quantities in the blood compared to triiodothyronine (T3).
* The thyroid hormone produce more thyroxine (T4) than triiodothyronine (T3)
32
99.5% of thyroid hormone is circulating in the blood in the bound state. Which protein does it bind to?
Plasma proteins:
1. Thyroxine binding globulin
2. Albumin
3. Transthyretin
All these plasma proteins are synthesized by the liver.
33
Thyroid hormone circulates in the bloodstream in two states. Name them?
Which component in the active/ regulated component
Bound (99.5%)
Free (0.5%)
Free is the active and regulated component- this component is the ones that act on peripheral tissues
34
Describe the thyroid hormone mode of action
* Upon entering the tissue cells, both thyroxine and triiodothyronine again bind with nuclear receptor, an intracellular receptors.
* Nuclear receptor binds to triiodothyronine (T3) more strongly than the thyroxine (T4).
* Therefore, they are again stored, but this time in the target cells themselves, and they are used slowly over a period of days or weeks.
* Much of the T3 is generated locally from T4 stores (varies between tissues)
* Cytosolic T3 is transported into the nuclei and binds to receptor causing the modulation of gene expression
35
Describe the importance of thyroid hormone in fetal development
* Thyroid hormone has widespread effects.
* In fetus the mothers thyroid hormone is essential. Fetal thyroid does not develop until a few weeks into gestation. Therefore it is through that the TH is important from the mother for the development of the fetal brain in these early stage.
36
Name some tissues the thyroid hormone effects
* Skeletal
* Bone turnover
* Cardiovascular
* Heart rate
* Metabolic
* lipids and glucose
37
Describe the regulation of thyroid hormone
* Thyroid stimulating hormone (TSH) from the anterior pituitary stimulates synthesis and secretion of T4 (mostly) and T3 from the thyroid.
* TSH secretion is inhibited by T4 and T3 (negative feedback)
* Thyroid-releasing hormone (TRH) from the hypothalamus stimulates TSH secretion.
* TRH is inhibited by T4 and T3 (negative feedback)
38
↑TSH + ↓T4 + ↓ T3 = which thyroid disease
Primary hypothyroidism
39
↓TSH + ↓T4 + ↓ T3 = which thyroid disease
Secondary hypothyroidism
40
↓TSH + ↑T4 + ↑T3 = which thyroid disease
Primary hyperthyroidism
41
In sick euthyroid, _____ TSH and ____ T4
Low TSH
Low T4
42
Primary hypothyroidism:
Blood test would show?
Cause?
Low T4 + T3.
High TSH.
Thyroid cause
43
Secondary hypothyroidism:
Blood test would show?
Cause?
Low T4 and T3
Low TSH
Pituitary cause
44
Name some causes of hyperthyroidism
* **Graves**’ **disease**
* **Toxic** **adenoma**- benign tumour of the thyroid
* **Multinodular** **goitre** - increase nodules on the gland
* **Thyroiditis**- inflammation of the thyroid- initally hyper but as the conditon processes can turn into hypo (as the tissue gets damaged)
* **Excess** **administration** **of** **thyroxine**
45
Define the term thyrotoxicosis
Means an excess of thyroid hormone in the body.
46
Describe the clinical signs and symptoms of hyperthyroidism
* Weight loss
* Tremor
* Heat intolerance
* Diarrhoea
* Palpitations
* Sweating
47
Describe the clinical signs and symptoms associated with Grave's disease
**Pretibial Myxoedema** - a dermatological condition where there are deposits of mucin under the skin on the anterior aspect of the leg. This gives a discoloured, waxy, oedematous appearance to the skin over this area. It is a reaction to the TSH receptor antibodies.
**Exopthalmos** - bulging of eyeball out of the socket caused by Graves Disease
**Thyroid acropachy** - clubbing of the fingers
48
Primary Hyperthyroidism is due to ____ pathology.
Thyroid
49
Secondary Hyperthyroidism is due to ____ pathology.
Pituitary
50
Ophthalmopathy in seen in \_\_\_% of Grave's disease patients
50%
51
Name the autoimmune thyroid disorder that causes hypothyroidism
Hashimoto thyroiditis
52
Name the autoimmune thyroid disorder that causes hyperthyroidism
Graves disease
53
Laboratory findings in Graves disease include ____ free T 4 and T 3 levels and _____ TSH levels.
A) elevated
B) lowered
54
Describe the pathogenesis of Grave's disease
An autoimmune disorder in which TH2 lymphocytes are inappropriately primed to recognise thyroid-stimulating hormone (TSH) receptors on thyroid follicle cells.
The activated TH2 cells stimulate B lymphocytes to produce TSH receptor antibody (type of IgG), mimicking TSH and results in an unregulated thyroid hormone production.
The result is high T4 and T3 with low TSH
55
Describe the pathogenesis of the exophthalmos symptom associated with Graves disease
The retro-orbital connective tissues suffer autoimmune attack by TSH receptor antibody because they express TSH receptors: causing proptosis, disturbance in gaze/vision and retraction of eyelids.
56
What are the main treatments options for hyperthyroidism (including Graves disease)
* Medicine (first line)
* Radioactive iodine treatment
* Surgery
57
Describe the medicine treatment option for hyperthyroidism
* Medicines called thionamides are commonly used to treat an overactive thyroid. They stop the thyroid producing excess hormones.
* The main types used are **carbimazole** and **propylthiouracil** (PPU)
58
What are the common side effects of the medicines available to treat hyperthyroidism
Carbimazole - Agranulocytosis (low white cell count) therefore increase risk of infections.
59
Medicine for treating hyperthyroidism takes how long for a patient to notice a benefit?
What is given in the meantime?
Takes approx. 1 to 2 months before the patient notices any benefit.
Patient may be given a beta blocker (-olol e.g. atenolol) to help relieve some symptoms before the hyperthyroid targeted medicines take an effect
60
Describe the radioactive treatment option for hyperthyroidism
Radioactive iodine is given to the patient. This destroys thyroid tissue by beta emission
61
What are the common side effects of radioactive iodine treatment for hyperthyroidism
* Hypothyroidism is main side effect
* May worsen graves disease particularly the eye disease
* Defer conception for at least 4 months
* Long term cancer risk
62
What are the common side effect of the surgical treatment for hyperthyroidism?
The surgery involves the removal of all or part of your thyroid may be recommended.
Thyroidectomy- surgical removal of the thyroid
* Haemorrhage: 0-1.3%
* Recurrent laryngeal nerve palsy- can lead to changes in the voice: 0-4.5%
* Permanent hypocalcaemia 0.6%
* Hypothyroidism
63
Describe the long term outcome for the medication treatment for hyperthyroidism
Once your thyroid hormone levels are under control, your dose may be gradually reduced and then stopped. But some people need to continue taking medicine for several years or possibly for life.
64
Name some of the causes of hypothyroidism
* Autoimmune thyroid disease (**Hashimotos**)
* **Thyroiditis**- inflammation of the thyroid gland
* **Thyroidectomy**- removal of the thyroid
* Following radio iodine therapy
* **Drug-induced**- lithium
* **Pituitary** **disease** - Secondary hypothyroidism
* Severe iodine deficiency
65
Hashimotos is more common in which gender
Females
66
Describe the clinical signs and symptoms of hypothyroidism
* Weight gain
* Depression
* Lethargy
* Constipation
* Cold intolerance
* Dry skin
* Anaemia
* Loss of the lateral third of eyebrow
67
Define goitre and why thyroid condition does it indicate?
It is a swelling of the thyroid gland that causes a lump in the front of the neck.
Not precise- can be formed in hypothyroidism and hyperthyroidism
68
Treatments available for hypothyroidism
* Daily hormone replacement tablets, called **levothyroxine**, to raise your thyroxine levels.
* Best taken on an empty stomach
* Avoid taking with proton pump inhibitors, ferrous sulphate or calcium
* Levothyroxine is T4 form so it needs to be converted by the body to T3.
69
How many iodine molecules can each tryosine in the thyroglobulin bind? what does it form?
Each tryosine can bind to a maximum of 2 iodine
1 tryosine + 2 iodine = DIT
1 tryosine + 1 iodine = MIT
