Lecture 29: Thyroid Gland Pharmacology

Question 1

What classes does the thyroid gland release?

Answer 1

• T3 (triiodothyronine) and T4 (thyroxine) thyroid hormones

* Calcitonin

Question 2

What is the most active thyroid hormone?

Answer 2

T3 (triiodothyronine)

Question 3

What causes the release of TSH from the anterior pituitary?

Answer 3

The release of TRH from the hypothalamus

Question 4

What is TRH and what does it do?

Answer 4

A hormone released from the hypothalamus that stimulates TSH to be released from the anterior pituitary

Question 5

What does TSH do?

Answer 5

It is released from the anterior pituitary and causes the release of T4 and T3 from the thyroid

Question 6

What inhibits the release of TRH from the hypothalamus?

Answer 6

T4 and T3 from the thyroid

Question 7

What inhibits the release of TSH from the anterior pituitary?

Answer 7

T4 and T3 from the thyroid

Question 8

What are the physiological effects of T4 and T3?

Answer 8

• Increased basal metabolic rate
• Sensitization to catecholamine (increased cardiac output, heart rate, breathing rate)
• Important role in growth and development

Question 9

What are Thyroid hormones made up of?

Answer 9

Two modified tyrosine molecules

Question 10

What is the precursor protein to Thyroid hormone and what is it rich in?

Answer 10

Thyroglobulin and it is tyrosine rich

Question 11

What happens to the tyrosines to make thyroid hormones?

Answer 11

• They are enzymatically iodinated

* The iodinated tyrosines are enzymatically coupled

Question 12

What does TSH stimulation do?

Answer 12

Causes the thyroid hormone precursor protein to be endocytosed and processed. And then T4 and T3 can be released

Question 13

Where does Iodination and coupling of thyroglobulin happen?

Answer 13

On the Apical side (follicle lumen)

Question 14

Where is Thyroglobulin processed after it has been iodinated and coupled?

Answer 14

Within the cell (so not the lumen of the follicle)

Question 15

Where are T4 and T3 released from after being generated from thyroglobulin?

Answer 15

The basolateral side of the cell, so to the bloodstream

Question 16

What are thyroid follicles?

Answer 16

Rings made up of multiple cells that form around a lumen

Question 17

What do the thyroid cells release into the follicle?

Answer 17

Thyroglobulin

Question 18

What does Thyroperoxidase do?

Answer 18

It iodinates and couples Thyroid hormone

Question 19

What happens if the thyroid is inactive?

Answer 19

The lumen of the gland will fill with colloid

Question 20

What is Colloid?

Answer 20

Fluid that is rich in unprocessed thyroglobulin that is waiting for the signal to be processed

Question 21

What does TSH trigger?

Answer 21

Exocytosis of thyroglobulin so it can be processed into T3 and T4

Question 22

How does the the Thyroid gland get iodine?

Answer 22

It concentrates iodine from the bloodstream using the Na+/I- cotransporter

Question 23

Where is Iodide transported?

Answer 23

To the follicle lumen and eventually added to thyroglobulin

Question 24

What kind of receptor is the thyroid hormone receptor?

Answer 24

An intracellular type receptor

Question 25

What does the thyroid hormone receptor do after binding of thyroid hormone?

Answer 25

Acts as a transcription factor after binding of thyroid hormone

Question 26

What do T3 and T4 need to do in order to bind the Thyroid hormone receptor?

Answer 26

They need to be taken up into cells by a transporter protein (instead of just diffusing through the membrane) in order to access the receptor

Question 27

Where is the receptor for T3 or T4 located?

Answer 27

In the nucleus already bound to transcription factors

Question 28

What happens with at rest/unbound thyroid hormone receptors?

Answer 28

They associate with response elements and recruit co repressors which weakens gene transcription

Question 29

What happens if T4 is taken up into a cell?

Answer 29

T4 is typically de-iodinated to form T3

Question 30

What does T3 binding in the nucleus cause?

Answer 30

It causes recruitment of RAR (retinoic acid receptor) to form a heterodimer with the thyroid hormone receptor

Question 31

What does the recruitment of coactivators when T3 is bound do?

Answer 31

Leads to enhanced transcription of gene

Question 32

How fast is T3 and T4 activation of receptors?

Answer 32

It is slow

Question 33

What is Hypothyroidism?

Answer 33

Deficient thyroid function (not enough release of thyroid hormone)

Question 34

What are the most common causes of Hypothyroidism?

Answer 34

* Iodine deficiency (dietary) * Autoimmunity towards thyroid (Hashimoto's thyroiditis) * Congenital defect * Inappropriate hormonal regulation (insufficient TSH or TRH)

Question 35

What are the symptoms of Hypothyroidism?

Answer 35

* Fatigue * Weight gain * Hypersensitivity to cold * Bradycardia

Question 36

What are the two types of Hypothyroidism?

Answer 36

Primary and Secondary hypothyroidism

Question 37

What causes primary hypothyroidism?

Answer 37

Defect in thyroid function

Question 38

What are the features of Hypothyroidism? (hormone levels)

Answer 38

Low T4 and T3 but high TSH

Question 39

What is the cause of Secondary Hypothyroidism?

Answer 39

•Central defect (poor function of anterior pituitary or hypothalamus)

Question 40

What are the feature of secondary hypothyroidism?

Answer 40

* Low T4 and T3 | * Low TSH

Question 41

Why does secondary hypothyroidism have low Low TSH and the other one has high TSH?

Answer 41

Because in primary hypothyroidism the gland is not producing enough T4 and T3 so there is no negative feedback inhibiting TSH. In Secondary hypothyroidism, the CNS us unable to release TSH

Question 42

What is the treatment for Hypothyroidism?

Answer 42

Hormone replacement with Synthetic thyroxine (levothyroxine)

Question 43

What is Hyperthyroidism?

Answer 43

Overactive Thyroid function (excessive production of thyroid hormone)

Question 44

What are the most common causes of Hyperthyroidism?

Answer 44

* Graves disease | * Hyperplasia of the thyroid

Question 45

What is Graves disease?

Answer 45

When stimulatory antibodies are released against the TSH receptor and activates them leading the excess thyroid hormone release

Question 46

What are the symptoms of Hyperthyroidism?

Answer 46

* Sleep difficulty * Heat (temperature) intolerance * Tachycardia * Weight loss * Tremor

Question 47

What is Graves disease caused by?

Answer 47

Stimulation of thyroid by anti-TSH receptor antibodies

Question 48

What are the features of graves disease? (Hormones)

Answer 48

* High T4 and T3 * Low TSH * Detection of anti-TSH antibodies * Bulging eyes

Question 49

What is Thyroid hyperplasia caused by?

Answer 49

Thyroid adenoma, goiter

Question 50

What are the features of Thyroid Hyperplasia? (hormones)

Answer 50

* High T4 and T3 | * Low TSH

Question 51

What is the cause of Secondary Hyperthyroidism?

Answer 51

Central defect (excessive production of TSH by anterior pituitary)

Question 52

What are the features of Secondary Hyperthyroidism? (hormones)

Answer 52

High T4 and T3 and high TSH

Question 53

What are the two Thyroid Autoimmune diseases?

Answer 53

Graves disease and Hashimoto's disease

Question 54

What happens in graves disease?

Answer 54

The antibodies cause stimulation of the TSH receptor

Question 55

What happens in Hashimoto's thyroiditis?

Answer 55

Antibodies recognize other thyroid-specific proteins and lead to damage of the thyroid

Question 56

What happens to the cells around the follicle when they become active?

Answer 56

The cells around become larger and the lumen becomes smaller

Question 57

What happens to the follicle in graves disease?

Answer 57

Hyperstimulation of the follicles and so they look like an active state where the cells are big and the lumen will shrink and all the colloid is used up and spit out as thyroid hormone

Question 58

What happens to the follicles in Hashimoto's thyroiditis?

Answer 58

Lymphocytes infiltrate the thyroid gland that attack the thyroid follicle and cause it to die

Question 59

What are some of the physical features of Hyperthyroidism?

Answer 59

* Exophthalmos (bulging eyes) | * Goiter (swelling in the neck)

Question 60

What are the four treatments of Hyperthyroidism?

Answer 60

* Surgery * Radioactive iodine treatment * Antithyroid drugs * Symptomatic treatment with beta-blockers

Question 61

What is the drawback to using surgery to treat hyperthyroidism?

Answer 61

* It can disrupt the parathyroid glands causing disturbances in Ca2+ * It needs management for hypothyroidism

Question 62

What is the approach for radioactive iodine treatment for Hyperthyroidism?

Answer 62

Iodine is concentrated within the thyroid and radiation leads to the destruction of the thyroid

Question 63

What are the drawbacks to radioactive iodine treatment?

Answer 63

It should not be used during pregnancy

Question 64

What is the approach to anti-thyroid drugs to treat hyperthyroidism?

Answer 64

They prevent several steps in T4/T3 synthesis

Question 65

What are the drawback to anti-thyroid drugs?

Answer 65

They have diverse side effects

Question 66

What is the approach to Symptomatic treatment of hyperthyroidism with Beta-blockers?

Answer 66

They may help with issues such as tachycardia

Question 67

What is the drawback to treatment of hyperthyroidism with betablockers?

Answer 67

It does not influence the underlying cause of the disease

Question 68

What is a drug to treat hyperthyroidism?

Answer 68

Thioamides (Methimazole)

Question 69

What is Methimazole used to treat?

Answer 69

Hyperthyroidism

Question 70

How does Methimazole work?

Answer 70

It prevents the iodination and coupling steps mediated by Thyroperoxidase