Thyroid Gland

Question 1

Give a brief overview of thyroid function.

Answer 1

• essential for normal development, especially the CNS and bone
• essential for normal metabolism of many body tissues

Question 2

What are the functions of the different cells in the thyroid?

Answer 2

• Follicular cells synthesise and secrete thyroid hormone.
• Colloid is where TH is stored.
• C-cells secrete calcitonin - to reduce plasma Ca2+

Question 3

Thyroid hormones are derived from two iodinated tyrosine molecules.
Describe two thyroid hormones learnt.

Answer 3

T4: major form released to blood, less active (prohormone)
T3: active form, converted in target cells

Question 4

What are the steps to TH synthesis? PART 1

Answer 4

• Active uptake of I- across the basolateral membrane, against the concentration gradient. Done by the Na/I symporter, and stimulated by TSH.
• Iodide efflux (by diffusion) then occurs across the apical membrane via pendrin exchanger

Question 5

What are the steps to TH synthesis? PART 2

Answer 5

• At the extracellular apical membrane, iodide is oxidised to iodine and covalently bind to tyrosine residues within thyroglobulin (TG) macromolecules.
• Requires TPO and H2O2.

Question 6

What are the steps to TH synthesis? PART 3

Answer 6

• Tyrosine residues may be iodinated in one (mono-iodotyrosine, MIT) or two (DIT) positions.
• Coupling of iodotyrosine residues produces T4 (DIT-DIT) and a smaller amount of T3 (DIT-MIT). Catalysed by TPO

Question 7

What are the steps to TH release? PART 1

Answer 7

• Under influence of TSH, colloid droplets consisting of thyroid hormones within TG molecules are taken back up into the follicular cells by pinocytosis.
• Fusion of the colloid droplets with the lysosomes causes hydrolysis of TG and release of T3 and T4.

Question 8

How do thyroid hormones circulate?

Answer 8

• Bound to plasma proteins.
• Mainly TBG (~70%), transthyretin (10-20%) and albumin (10-20%).

Question 9

How do thyroid hormones act on target tissues? PART 1

Answer 9

• TH receptors (TRs).
• Belong to the nuclear receptor superfamily - high affinity for T3
• Ligand-activated transcription factors.

Question 10

How do thyroid hormones act on target tissues? PART 2

Answer 10

• Activation requires dimerisation with another TR or a retinoid X receptor (RXR).
• TRs are encoded by two genes: TR α and TR β.

Question 11

Describe the metabolic regulation of THs.

Answer 11

• Done by selenodeiodinases, abbreviated to D1-3.
• Used selenium as their trace element, so it is essential in the diet.
• Regulate the amount of T3 available to bind with the receptor.

Question 12

Outline the functions of the selenodeiodinases.

Answer 12

• Activate by converting T4 to T3 (D2)
• Inactivate by converting T3 to T2 (D3)
• Inactivate by converting T4 to rT3 (D3).

Question 13

What are some ways TH increases metabolic rate?

Answer 13

• affects number and size of mitochondria, enzymes, Na/K ATPase activity, etc.
• positive inotropic and chronotropic effects on the heart
• synergises with the sympathetic nervous system

Question 14

What are some ways TH is involved in energy metabolism?

Answer 14

• antagonises insulin signalling
• gluconeogenesis, lipolysis

Question 15

Describe how TH moves across the membrane.

Answer 15

• HYPOTHESIS: TH diffused across the cell membrane to work.
• TRUTH: TH transporters are required to allow TH across membrane e.g MCT8.

Question 16

What genetic mutation is MCT8 linked to?

Answer 16

Allan-Herndon-Dudley Syndrome

Question 17

Describe the role of the hypothalamic-pituitary-thyroid axis.

Answer 17

• Negative feedback control of thyroid hormone synthesis and secretion
• Hypothalamic neurosecretory cells release TRH into the portal capillaries.
• TRH stimulates thyrotrophs of the anterior pituitary to secrete TSH.

Question 18

What happens with high levels of T4 and T3?

Answer 18

• Release of TSH and TRH are turned down.

Question 19

Describe congenital hypothyroidism.

Answer 19

• Inadequate thyroid hormone production in neonates.
• Occur because of anatomic defects in gland, an inborn error of thyroid metabolism, or iodine deficiency.

Question 20

How is congenital hypothyroidism investigated and treated in neonates?

Answer 20

• Preventable with a simple neonatal heel prick before testing for TSH levels.
• Possible congenital hypothyroidism if the levels of TSH are high.

Question 21

Describe the TSH receptor and its actions.

Answer 21

• G-protein coupled receptor
• Done through Adenylate Cyclase (αGs and the cAMP-PKA cascade).
• Leads to iodide uptake, the transcription of NIS (Na+/I- symporter), TG and TPO, etc.

Question 22

What are the actions of TSH?

Answer 22

• increases iodine uptake
• stimulates other reactions involved in TH synthesis (eg. TPO)
• stimulates uptake of colloid
• induces growth of the thyroid gland (which can lead to goitre)

Question 23

Define hyperthyroidism.

Answer 23

• Occurs when there is TH excess.
• Primary - problem with the thyroid gland
• Secondary - problem with pituitary regulation

Question 24

Define hypothyroidism.

Answer 24

TH deficiency

Question 25

Describe Grave’s Disease.

Answer 25

- Common cause of primary hyperthyroidism. - Autoimmune disease characterised by high levels of circulating TH/ low levels of TSH. - Antibodies are directed to the TSH receptor - work as pharmacological agonists, so we end up with unregulated overproduction of TH.

Question 26

What are the symptoms of Grave's Disease?

Answer 26

- Weight loss (due to the increased metabolism) - Tachycardia - Fatigue - Diffuse goitre (due to TSH receptor stimulation) - Ophthalmopathy (an inflammatory disorder of the orbit and periorbital tissues).

Question 27

Describe Hashimoto’s Disease.

Answer 27

- Cause of hypothyroidism. - Autoimmune disease characterised by low levels of circulating TH/high levels of TSH. - Antibodies cause thyroid destruction and dysfunction.

Question 28

What are the symptoms of Hashimoto's Disease?

Answer 28

- Lethargy - Weight gain - Lack of growth and development - Diffuse goitre.

Question 29

What are the 2 main branches that supply the thyroid?

Answer 29

- Inferior thyroid artery - subclavian - Superior thyroid artery - carotid

Question 30

What is reverse T3?

Answer 30

- Iodinated on a different side - Inactive

Question 31

What 2 factors stimulate the hypothalamus to produce TH?

Answer 31

- Stress - Cold

Question 32

Why is high TSH and high TRH indicative of HYPOthyroidism?

Answer 32

→ If thyroid isn’t producing T3 or T4 → There is no negative feedback → TRH and TSH concentration are high

Question 33

What is the diagnosis for low TRH and low TSH but high T4 and T3?

Answer 33

Primary hyperthyroidism

Question 34

What is the diagnosis for high TRH & TSH but low T4 and T3?

Answer 34

Primary hypothyroidism

Question 35

What is the diagnosis for low TRH, high TSH and high T4 and T3?

Answer 35

Secondary hyperthyroidism