The thyroid and iodothyronines

Question 1

Draw a diagram showing the follicular cells, parafollicular cells(C cells) and the colliod

Answer 1

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Question 2

Draw the thyriod gland showing the pyramid, the isthmus, trachea and the thriod glands

Answer 2

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Question 3

What is colliod?

Answer 3

Colloid = proteinaceous substance found inside the follicles

Question 4

What are the parafollicular cells funcction?

Answer 4

Parafollicular cells (also called C cells) are neuroendocrine cells in the thyroid which primary function is to secrete calcitonin.

Question 5

What are follicular cells?

Answer 5

Follicular cells (also called thyroid epithelial cells or thyrocytes) are cells in the thyroid gland that are responsible for the production and secretion of thyroid hormones thyroxine (T4) and triiodothyronine (T3)

Question 6

Why is the pyramid in the thyriod gland clinically important?

Answer 6

PYARMID = the bit of tissue on the top of the isthmus which is present in some people (important clinically because a thyroid tumour could be in the pyramid

Question 7

Why is another name for T4?

Answer 7

thyroxine

Question 8

What is another name for T3?

Answer 8

triiodothyronine (T3)

Question 9

List the steps for the production of T3 and T4 and also draw a diagram?

Answer 9

1) Thyriod Stimulating Hormone (TSH) binds to the TSH receptor. This stimulates a number of steps that leads the synthesis of the thyriod hormones.
2) Iodide is transported from the blood into the follicular cells by a sodium iodide symporter. The iodine is transported with a saodium ion. NIS= Sodium iodide sympoter. NEED TSH RECEPTOR ACTIVIATION TO TAKE UP IODIDE.
3) Iodide is transported through the follicular cell and through the pendrin channel and finally into the Colliod.
4) TSHR activation effects the nucleus and leads to the synthesis of thyroglobulin (protein) which is transported into the colliod.
5) TSH also stimulates THYROID PEROXIDASE (TPO) enzyme
6) TSH also stimulates the Thyriod peroxidase enzyme (TPO)
7) TPO in the presence of Hydrogen Peroxide H202 converts iodide into a reactive iodine form which is short lived.
8) The reactive iodine in the presence of is added to TG in a process called iodination. The tyrosil residues become iodinated in one or more positions.

Thyroglobulin is a long array of amino acids which have a certain number of TYROSYL RESIDUES which become iodinated by the reactive iodine.
The tyrosyls can be iodinated in one or two positions to form MONOIODOTYROSINE (MIT) and DIIODOTYROSINE (DIT)

9) A coupling reaction then occurs which is catalised by Thyriod peroxidase enzyme (TPO) in the presence of hydrogen peroxide. Triiodothyronines (T3) and Tetraiodothyronines (T4) are formed. Linking two molecules of DIT produces T4. Combining one particle of MIT and one particle of DIT produces T3.
10) Thyroglobulin is now linked to T3 and T4. This molecule is the taken back into the thyriod follicular cell by endocytosis and fuses with a lysosome. Enzymes in the T3 and T4 break down the enzyme liberating T3 and T4 which can then move back into the blood.

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Question 10

Why is Thyriod peroxidase enzyme very important clinically expecially with the illness hyperthriodism?

Answer 10

If someone has an overactive thyriod gland and secreting too much throxine then carbimazole can be given which can inhibit thyriod peroxidase.

Question 11

Name these two molecules at the bottom.

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Answer 11

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Question 12

How are thyriod hormones mostly transported in the blood?

Answer 12

They are mostly bound to plasma proteins.

Question 13

Name the 3 plasma proteins that are bound to the thyriod hormones when they are transported in the blood?

Answer 13

Thyriod binding globulin
Albumin
Prealbumin

Question 14

What percentage of Thyriod hormones are bound to Thyroid-binding hormone, Albumin and prealbumin?

Answer 14

Thyriod binding globulin-70-80%
Albumin-10-15%
Prealbumin aka transthyretin- the rest prealbumin

Question 15

What percentage of T4 is unbound to a protein in the blood?

Answer 15

0.05%

Question 16

What percentage of T3 is unbound to a protein in the blood?

Answer 16

0.5%

Question 17

What makes iodothyroninces bioactive components?

Answer 17

The BIOACTIVE iodothyronines are the FREE MOLECULES which are NOT bound to plasma proteins

Question 18

What is the difference to iodothyronines bound to plasma proteins and ones not bound to plasma proteins?

Answer 18

The unbound ones of BIOACTIVE.

Question 19

What is the main product of the thyriod gland?

Answer 19

T4

Question 20

What is more active— T3 or T4?

Answer 20

T3

Question 21

What happens when T4 enters target tissues?

Answer 21

Deiodinated to T3 (bioactive form) in target tissues

T3 is what bonds to nucleur receptors and brings about its effects.

Question 22

Name the two molecules that are formed when T4 is deiodinated?

Answer 22

T3- Biologically active
Reverse T3- BIOLOGICALLY INACTIVE

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Question 23

Is T3 biologically active or inactive?

Answer 23

Active

Question 24

Is reverse T3 Biologically active or inactive.

Answer 24

REVERSE T3 (rT3) is BIOLOGICALLY INACTIVE

Question 25

What happens to T4 when you want reduced metabolism?

Answer 25

In situations where you want reduced metabolism (e.g. starvation) then T4 tends to be converted to rT3 rather than T3.

Different deiodinases ( enzymes that remove iodine molecules) regulate how much active T3 you have against inactive rT3.

Question 26

Draw a diagram showing what happens when T3 and T4 reach a cell?

Answer 26

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Question 27

Why do pateints with an overactive thyriod suffer from tachycardia, sweating profusely, high heart rate and tremor.

Talk about how excess Thyriod hormone brings about these effects?

Answer 27

T3 goes to the nucleus and regulates and stimulates the transcription of various genes, brings about the synthesis of various proteins. For example receptors for catacolamine ( beta-adrenergic). If you have a patient with overctive thyriod they will be tachycardic, they feel their heart pounding, they have tremor and sweating.

Question 28

What disease occurs when a baby has congenitial hypothyriodism which is left untreated?

Answer 28

Cretinism

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Question 29

What test is done in a hospital to prevent cretinism?

Answer 29

TH & TSH measured in new-born infant’s heel-prick test

Question 30

List the effects of thyriod hormone?

Answer 30

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Increase in Basal Metabolic Rate - Increase Protein, Carbohydrate and Fat metabolism

Potentiate actions of catecholamines- tachycardia and lipolysis

Effects on the Gi, CNS, reproductive system-

Effects fetal growth and development

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Question 31

What is the most common cause of hyperthriodism?

Answer 31

Graves disease add pic

Question 32

List the symptoms of hypothyriodism and hyperthyriodism?

Answer 32

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Patients with hyperthyriodism lose weight but they still have a good appetite.

They may have irregular periods and infertility.

Question 33

Why do pateints with hypothyriodism present with yellowish skin?

Answer 33

Thyriod hormones INCREASES VITAMIN C SYNTHESIS FROM RETINAL

Hypothyroidism leads to build up of retinal in the blood leading to yellowish skin coloration

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Question 34

What is the latent period and half lives for thyriod hormones and why is this clinically important?

Answer 34

Latent period:
T3: ~ 12h
T4: ~ 72h

Half lives:
T4 around 7-9 days
T3 around 2 days

Sometimes in clinical medicine you may have to withdraw a treatment for example if the patient is having a scan or an investigation. How long do you need to stop it for? the half life allows you to answer this?

Question 35

Explain the Hypothalamo-pituitary-thyroidal axis and draw a picture?

Answer 35

Neurones originating from the hypothalamus release Thyrotrophin Releasing Hormone (TRH) into the primary capillary plexus .

TRH passes down the portal vessels to the adenohypophysis where it’ll bind to membrane receptors (NOTE: TRH is a glycoprotein)

TRH will work on thyrotrophs to produce thyrotrophin

Thyrotrophin then has lots of effects on the follicular cells in the thyroid

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Question 36

What is the Wolff Chaikoff effect?

Answer 36

Large doses of stable iodine( inorganic iodide) acutely inhibit thyroid hormone synthesis (Wolff–Chaikoff effect) and thyroid hormone release.

Question 37

What causes an INCREASES IODOTHYRONINE PRODUCTION?

Answer 37

Thyroid Releasing Hormone

Oestrogens

Question 38

What decrease DECREASES IODOTHYRONINE PRODUCTION.

Answer 38

T3 and T4- Directly on adenohypophysis and Indirectly on hypothalamus.

Somatostatin

Glucocorticoids

Ingestion of large amounts of inorganic iodide (Wolff-Chaikoff Effect)

Question 39

Draw the Hypothalamus-putituary- thalamus axis?

Include in the diagram the postive and negative feedback arrows and what causes an increase or decrease in thryoid hormones?

Answer 39

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Question 40

If someone has damage to the thyriod gland by an autoimmune condition,and they are not making T3 or T4. What would you expect their TSH levels to be?

Answer 40

Very high

This is why in a heel prick test they check the TSH level, if it is high then the baby has congenital hypothyriodism.

Question 41

How is the wolff-Chaikoff effect used clinically?

Answer 41

We use that clinically if a patient is undergoing surgery for an overactive thyriod or if they have an thyrotoxic crysis in which they are releasing a lot of thyriod hormones. We give them pottasium iodide, and that high conc of iodide inhibits thyriod hormone synthesis for the first ten days. They might have an escape after 10 days because they dowb regulate symporters.