Thyroid Hormone - Thyroid Gland

Question 1

what cells are responsible for thyroid hormone production?

Answer 1

thyroid follicular cells

Question 2

why is iodine important in the diet?

Answer 2

to help in thyroid hormone synthesis

Question 3

what amino acid are thyroid hormones formed from?

Answer 3

tyrosine

Question 4

what active forms of the thyroid hormone are also released into the bloodstream?

Answer 4

thyroxin (T4) and tri-iodothyronine (T3)

Question 5

what is the major secreted product from the thyroid gland?

Answer 5

T4 - thyroxin

Question 6

which is more active T4 or T3

Answer 6

T3 - iodothyronine

Question 7

what binds to T3 and T4 in the circulation?

Answer 7

thyroxine-binding globulin (TBG)

Question 8

what is used to convert T4 to T3 at the liver, kidney and other tissues with high blood flow?

Answer 8

5’-deiodinase

Question 9

How does T3 regulate gene transcription?

Answer 9

1. The Thyroid hormone receptor (TR) is in the nucleus, bound to retinoid x receptor (RXR) to form a dimer
2. This dimer is bound to a thyroid response element (TRE) in the promoter region of hormone-sensitive genes.
3. In the absence of T3 the dimer binds to a co-repressor protein (CoR) that silences transcription
4. When T3 enters the nucleus, it displaces CoR and allows co- activator proteins (Co-A) to bind to the complex
5. this then regulates gene transcription

Question 10

how are thyroid hormones (T3 and T4 ) released?

Answer 10

1. Hypothalamic nuclei releases Thyrotrophin releasing hormone (TRH)
2. This stimulates the pituitary gland to release thyroid stimulating hormone (TSH)
3. This then acts on the thyroid gland to release thyroid hormones (T3 & T4)

Question 11

What four things does the TSH released from the pituitary gland increase?

Answer 11

1. increases iodine uptake
2. increases thyroglobulin synthesis
3. increases endocytosis and proteolysis of thyroglobulin
4. increases blood flow through the thyroid gland

Question 12

what causes the negative feedback loop on the pituitary and hypothalamus when T3 and T4 have been released?

Answer 12

when the T3 levels are high, a negative feedback loop occurs to slow down/ stop their release

Question 13

what are the roles of thyroid hormone?

Answer 13

1. role in metabolism

2. role in growth and development

Question 14

what are the metabolic functions of thyroid hormones?

Answer 14

1. Carbohydrate metabolism - increased glycolysis, increased insulin secretion etc
2. Fat metabolism - reduced fat stores, increased fatty acid conc in plasma etc
3. Protein metabolism - increased protein degradation, loss of muscle mass providing fuel for gluconeogenesis

Question 15

what is the effect of the thyroid hormone on the cardiovascular system?

Answer 15

1. increased cardiac output
2. increased heart rate
3. increased ventilation rate
4. increased sympathetic activity by potentiating catecholamine effects

Question 16

what occurs when there is a Thyroid deficiency during development?

Answer 16

cretinism (congenital hypothyroidism)

Question 17

what is the role of the thyroid hormone in growth?

Answer 17

Thyroid hormone is needed to allow bone, cartilage and other connective tissues to respond to growth hormone

Question 18

what is the most common cause of congenital hypothyroidism?

Answer 18

iodine deficiency

Question 19

what is the effect of a lack of iodine in your diet and how does this cause enlarged thyroid glands?

Answer 19

1. If iodine in diet is limited, little thyroid hormone can be synthesised
2. Plasma levels of TSH will therefore rise since no negative feedback
3. High levels of TSH will produce hypertrophy / hyperplasia of thyroid gland
4. Increased mass of tissue will produce more thyroid hormone - thyromegaly
5. In extreme cases – can lead to the development of a goitre

Question 20

where is the main source of iodine in diet?

Answer 20

• sea food / marine salts

- Regions very remote from sea mainly use rock salt in diet

Question 21

what condition can cause high TSH secretion besides a lack of iodine in the diet?

Answer 21

A pituitary tumour

Question 22

what is hyperthyroidism and what is the most common cause of hyperthyroidism?

Answer 22

it is an overactive thyroid gland in which excess thyroid hormone is released and it is most commonly caused by Graves disease.

Question 23

what happens in graves disease to cause hyperthyroidism?

Answer 23

B-lymphocytes secrete glycoproteins which activate the TSH receptors on the thyroid gland stimulating thyroid hormone release

Question 24

what pharmacological treatment is given for hyperthyroidism?

Answer 24

Thioamides (e.g. methimazole)

Question 25

how does the thioamine methimazole work?

Answer 25

inhibits T3/T4 synthesis by inhibiting thyroid peroxidase

Question 26

what is hypothyroidism and what is the most common cause of hypothyroidism?

Answer 26

it is an underactive thyroid gland in which little to no thyroid hormone is released and it is most commonly caused by cause Hashimoto thyroiditis – autoimmune destruction of thyroid follicular cells. A lack of thyroid hormone being released results in high TSH levels.

Question 27

in which will TSH levels be raised: hypothyroidism or hyperthyroidism?

Answer 27

hypothyroidism

Question 28

what is used to treat hypothyroidism?

Answer 28

Levothyroxine - T4 | L-tri-iodothyronine (T3) for faster action

Question 29

where are parathyroid glands found and what do they do?

Answer 29

- found behind the thyroid: Two on each side of body | - Secrete parathyroid hormone

Question 30

what does parathyroid hormone do?

Answer 30

plays a crucial role in the control of circulating Ca2+ levels

Question 31

what happens to the parathyroid gland when calcium levels changes?

Answer 31

1. Cells of parathyroid gland express a G protein-coupled receptor for Ca2+ 2. If [Ca2+ ] is high – PTH secretion inhibited 3. If [Ca2+] is low – PTH is secreted 4. This means that circulating [PTH] is dependent upon circulating [Ca2+]

Question 32

how is Vitamin D activated by parathyroid hormone (PTH) and Calcium?

Answer 32

1. Vitamin D is metabolically inactive and must undergo 2 hydroxylation reactions to become active: - First occurs in the liver - Can undergo one of two reactions in kidney catalysed by aromatases: - Hydroxylation at 1 position (1alpha- aromatase) leads to activation - Hydroxylation at 24 position (24alpha- aromatase) leads to inactive metabolite 2. Low [Ca2+] and PTH both stimulate 1a- aromatase therefore PTH (and low [Ca2+]) stimulate activation of vitamin D

Question 33

how does vitamin D increase circulating calcium concentration?

Answer 33

1. Stimulates the absorption of Ca2+ by the small intestine – increases amount of Ca2+ obtained from diet 2. Stimulates reabsorption of Ca2+ from the glomerular filtrate – this reduces the amount of Ca2+ lost in the urine 3. Stimulates Ca2+ release from bone

Question 34

how does PTH control calcium levels?

Answer 34

- when low levels of Calcium present, PTH is released - This stimulates 1,25-(OH)2-cholecalciferol (vitamin D) - vitamin D then causes Ca2+ levels to increase in the blood

Question 35

what is the direct effect of PTH on bone?

Answer 35

1. PTH receptors are found on osteoblasts (bone formation) but not on osteoclasts (bone degradation) 2. Initially PTH activates osteoblasts and evokes transient deposition of bone 3. Long term stimulation of osteoblasts leads to release of cytokines from osteoblasts 4. These cytokines stimulate the numbers and activity of bone degrading osteoclasts 5. Long term effect of PTH stimulation is therefore to promote the release of Ca2+ from bone 6. Restores circulating Ca2+ levels

Question 36

what hormone is released by the parafollicular cells found in the thyroid gland?

Answer 36

calcitonin

Question 37

how does calcitonin control Ca2+ levels?

Answer 37

1. Calcitonin is secreted in response to elevated [Ca2+] 2. Calcitonin decreases activity of osteoclasts so tends to shift balance in favour of deposition of Ca2+ in bone hence reducing plasma calcium levels 3. Calcitonin has weak effects on kidney which favour a loss of Ca2+ from body via urine