S7) The Thyroid Gland

Question 1

Briefly, describe the structure of the thyroid gland

Answer 1

2 lobes joined by isthmus

Question 2

Describe the location of the thyroid gland

Answer 2

• Lies against and around front larynx and trachea
• Below thyroid cartilage
• Isthmus extends from 2nd to 3rd rings of the trachea

Question 3

Thyroid is first endocrine gland to develop.

In 5 steps, describe the embryological development of the thyroid gland

Answer 3

⇒ Appears as an epithelial proliferation in floor of pharynx at base of tongue

⇒ Descends as diverticulum through thyroglossal duct

⇒ Migrates downwards in front of hyoid bone

⇒ Remains connected to tongue by thyroglossal duct

⇒ Duct degenerates and detached thyroid continues to final position

Question 4

Describe the microscopic structure of the thyroid gland

Answer 4

• Follicular cells arranged in spheres called thyroid follicles
• Follicles filled with extracellular colloid, a deposit of thyroglobulin

Question 5

The thyroid and parathyroid are distinct glands.

Describe how their cells vary in terms of hormone production

Answer 5

Question 6

Describe how thyroid hormones are formed

Answer 6

2 tyrosine molecules are linked together with iodine at 3/4 positions on the aromatic rings

Question 7

What is the role of thyroglobulin in thyroid hormone formation?

Answer 7

Thryoglobulin acts as a scaffold on which thyroid hormones are formed

Question 8

What is thyroid peroxidase and what does it do?

Answer 8

Thyroid peroxidase is a membrane bound enzyme that regulates thyroid hormone synthesis

Question 9

Thyroid peroxidase regulates 3 separate reactions involving iodide.

Identify these

Answer 9

• Oxidation of iodide to iodine (requires H₂O₂)
• Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin
• Coupling of MIT/DIT to generate thyroid hormones within the thyroglobulin protein

Question 10

How is dietary iodine absorbed in the thyroid gland?

Answer 10

• Iodine is oxidised to iodide before absorption in the small intestine
• Iodide (I^-) is taken up from blood by thyroid epithelial cells via a sodium-iodide symport

Question 11

Explain the following statement: most of T₄ is converted to T₃ outside of the thyroid

Answer 11

• 90% of thyroid hormone secreted is T₄
• Most T₄ is converted to T₃ in the liver & kidneys
• 80% of circulating T₃ is derived from T₄

Question 12

Which thyroid hormone is more biologically active?

Answer 12

Biological activity of T₃ is 4x that of T₄

Question 13

How are the thyroid hormones transported in the blood?

Answer 13

T₃ & T₄ are transported in blood bound to the protein thyroxine-binding globulin

Question 14

Thyroid hormones effect virtually every cell in the body and have two interconnected responses.

What are these?

Answer 14

• Effects on cellular differentiation and development
• Effects on metabolic pathways

Question 15

Regulation of thyroid hormone secretion is via negative feedback.

Outline this

Answer 15

Question 16

Describe the structure of thyroid stimulating hormone

Answer 16

Glycoprotein hormone composed of 2 non-covalently bound subunits:

• α subunit is also present in FSH and LH
• β subunit provides unique biological activity

Question 17

TSH is a trigger for thyroid hormone release.

Identify the seven processes stimulated sequentially

Answer 17

⇒ Iodide uptake

⇒ Iodide oxidation (iodine)

⇒ Thyroglobulin synthesis

⇒ Thyroglobulin iodination

⇒ Colloid pinocytosis into cell

⇒ Proteolysis of thyroglobulin

⇒ Cell metabolism & growth

Question 18

Describe the cellular mechanisms involved in the TSH induced signalling pathway for thyroid hormone secretion

Answer 18

Question 19

Identify the three general effects of thyroid hormones on the body

Answer 19

• Increase in BMR and heat production
• Stimulation of metabolic pathways
• Sympathomimetic effects

Question 20

How do thyroid hormones increase BMR and heat production?

Answer 20

• Increases number and size of mitochondria
• Stimulates synthesis of enzymes in respiratory chain

Question 21

Describe two metabolic pathways stimulated by thyroid hormones

Answer 21

Catabolic pathways:

• Lipid metabolism – lipolysis and β-oxidation
• Carbohydrate metabolism – insulin-dependent entry of glucose into cells, gluconeogenesis and glycogenolysis

Question 22

What are the sympathomimetic effects of thyroid hormones?

Answer 22

Sympathomimetic effects – increases target cell response to catecholamines by increasing receptor number

Question 23

Identify the tissue specific effects of thyroid hormones in terms of the following:

• Cardiovascular system
• Nervous system

Answer 23

• CVS – increases heart’s responsiveness to catecholamines (increased cardiac output and peripheral vasodilation)
• Nervous system – myelination of nerves & development of neurones

Question 24

Describe the function and action of thyroid hormone receptors

Answer 24

• Function as hormone-activated transcription factors
• Act by modulating gene expression

Question 25

In four steps, outline the cell signalling pathway induced by thyroid hormones on intracellular receptors

Answer 25

Question 26

Indicate the normal plasma levels of thyroid hormones as well as reasons for variations unrelated to thyroid disease

Answer 26

Question 27

What is goitre?

Answer 27

- **Goitre** is the enlargement of the thyroid gland due to its overstimulation - It may accompany either hypo- or hyperthyroidism

Question 28

What is hypothyroidism?

Answer 28

**Hypothyroidism** is an endocrine disorder wherein the thyroid gland is underactive and produces an insufficient amount of T₃/T₄

Question 29

How does a patient with hypothyroidism present?

Answer 29

- Obesity - Lethargy - Intolerance to cold - Bradycardia - Dry skin - Alopecia

Question 30

What are the thyroid function test results for a patient with hypothyroidism?

Answer 30

- Low T₃ - Low T₄ - Elevated TSH

Question 31

Identify 6 possible causes of hypothyroidism

Answer 31

- Failure of thyroid gland - Congenital (TSH/TRH deficiency) - Inadequate dietary supply of iodine - Autoimmunity - Post surgery - Anti-thyroid drugs

Question 32

Severe hypothyroidism in infants is referred to as cretinism. How does this present?

Answer 32

- Dwarfed stature - Mental deficiency - Poor bone development - Slow pulse - Muscle weakness

Question 33

Severe hypothyroidism in adults is referred to as myxedema. How does this present?

Answer 33

- Thick puffy skin - Muscle weakness - Slow speech - Mental deterioration - Intolerance to cold

Question 34

What is Hashimoto's disease?

Answer 34

- **Hashimoto's disease** is an autoimmune disease resulting in destruction of thyroid follicles, leading to hypothyroidism - Is is 5x more common in women and goitre may be present

Question 35

What are the thyroid function test results for a patient with Hashimoto's?

Answer 35

- Low T₃ - Low T₄ - Elevated TSH

Question 36

How is Hashimoto's disease treated?

Answer 36

Oral thyroid hormone (T₄ – longer half-life)

Question 37

What is hyperthyroidism?

Answer 37

**Hyperthyroidism** is an endocrine disorder wherein the thyroid gland is overactive and produces an excess amount of T₃/T₄

Question 38

How does a patient with hyperthyroidism present?

Answer 38

- Weight loss - Irritability - Heat intolerance, sweating warm vasodilated hands - Tachycardia - Fatigue, weakness

Question 39

Identify 6 possible causes of hyperthyroidism

Answer 39

- Autoimmune - Toxic multinodular goitre - Toxic adenoma / thyroid carcinoma - Excessive T₄/T₃ therapy - Drugs *e.g. amiodarone* - Ectopic thyroid tissue

Question 40

What is Graves' disease?

Answer 40

- **Graves' disease** is an autoimmune disease resulting in hyperthyroidism caused by the production of thyroid stimulating immunoglobulin (TSI) - TSI continuously stimulates thyroid hormone secretion outside normal negative feedback control

Question 41

How does Graves' disease present?

Answer 41

- Increased BMR - Excessive sweating - Decrease in body weight - Muscle weakness - Heart palpitations - Exopthalmos (not always)

Question 42

What are the thyroid function test results for a patient with Graves' disease?

Answer 42

- Increased T₃ - Increased T₄ - Very low TSH

Question 43

How is Grave's disease treated?

Answer 43

**Antithyroid drugs** are used to treat overactive thyroid

Question 44

Carbimazole is the most commonly used antithyroid drug in the UK. Describe the mechanism of its action

Answer 44

- Carbimazole **block formation** of thyroid hormone - Carbimazole is a **pro-drug** and is converted to methimazole in body - Prevents **thyroid peroxidase from coupling and iodinating tyrosines** on thyroglobulin

Question 45

Which imaging technique is used to visualise the thyroid gland and how is it performed?

Answer 45

**Thyroid scintigraphy** – technetium-99m (99mTc) used for isotope scanning of the thyroid with a gamma camera