Physiology of Thyroid Gland

Question 1

What does the follicular structure of the thyroid gland contain?

Answer 1

Colloid

Question 2

What is colloid?

Answer 2

Proteinaceous material that is an extracellular storage form of thyroid hormone

Question 3

What are follicles lined by?

Answer 3

Single layer of epithelial cells

Question 4

What is the function of follicular cells?

Answer 4

Synthesise and secret thyroid hormones in response to anterior pituitary TSH

Question 5

What cell is found in the intrafollicular region?

Answer 5

Parafollicular or C cells

Question 6

What do parafollicular cells secrete?

Answer 6

Peptide hormone called calcitonin - plays a role in Ca2+ homeostasis

Question 7

What are the two thyroid hormones?

Answer 7

T3 and T4

Question 8

What does T3 and T4 synthesis require?

Answer 8

Iodine at C3 and C5 positions

Question 9

What is the polarity of T3 and T4?

Answer 9

Moderately polar with limited solubility in plasma

Question 10

What does the AIT apical transporter do?

Answer 10

Moves iodine into colloid area for T3 and T4 synthesis

Question 11

What is T3 and T4 bound to for storage

Answer 11

Thyroglobulin

Question 12

What does thyroid peroxidase use to oxidase I- to I/I+?

Answer 12

H2O2 generated by 2 other enzymes (DUOX1 and 2)

Question 13

What does TSH promote?

Answer 13

Endocytosis

Question 14

What does secretion of thyroid hormones require?

Answer 14

Endocytosis of colloid (containing thyroglobulin and bound hormones) back into follicular cells

Question 15

Which thyroid hormone is secreted most?

Answer 15

T4 ~ 80mg/day (>90% of output)

Question 16

Which thyroid hormone is more potent?

Answer 16

T3

Question 17

Which thyroid hormone has a greater half life and why?

Answer 17

T4 as it binds more avidly to its binding proteins

Question 18

What is the major plasma transport protein?

Answer 18

Thyroxine binding globulin > transthyretin > albumin

Question 19

What enzyme converts T4 to T3 in target cells?

Answer 19

5’ monodeiodinase

Question 20

When is 5’ monodeiodinase less active?

Answer 20

During fasting/starvation and cortisol excess

Question 21

What does 5’ monodeiodinase inactivate?

Answer 21

T3 in liver and other tissues (inner C5 position)

Question 22

What is rT3?

Answer 22

Competitive inhibitor of T3

Question 23

What increases rT3 production and thus decreased T3?

Answer 23

Cortisol excess (euthyroid sick syndrome)

Question 24

What are thyroid hormones MoA?

Answer 24

1. Entry into cells
2. Deiodination
3. Non genomic actions
4. Nuclear import
5. Binding to TH receptor, formation of heterodimer with retinoic acid receptor and binding to TRE
6. Recruitment of co-activator proteins

Question 25

What is the Basal metabolic rate?

Answer 25

Metabolic rate of awake relaxed person 12-14 hrs after eating at comfortable temperature

Question 26

What is BMR highly influenced by?

Answer 26

Thyroid hormone levels High BMR = hyperthyroidism Low BMR = hypothyroidism

Question 27

What 6 things do thyroid hormones increase?

Answer 27

Size and number of mitochondria Oxygen consumption ATP production Activity of key metabolic enzymes Protein and lipid turnover BMR

Question 28

Why are thyroid hormones essential for normal growth?

Answer 28

Role in protein synthesis Increases energy production and substrate availability Permissive for anabolic actions of growth hormone

Question 29

What role do thyroid hormones play in CNS development?

Answer 29

Promotes nerve growth Growth of dendrite cells Myelin formation

Question 30

What is cretinism?

Answer 30

Thyroid hormone deficiency - Impaired CNS development, intellectual and development disability

Question 31

What does maternal and/or fetal hypothyroidism cause?

Answer 31

Delayed CNS development and intellectual disability

Question 32

What secrets thyroid stimulating hormone?

Answer 32

Anterior pituitary

Question 33

What does TSH stimulate?

Answer 33

stimulates follicular cell growth, follicle formation and maintenance and growth of thyroid gland

Question 34

What secrets TRH?

Answer 34

Hypothalamus

Question 35

What does TRH regulate?

Answer 35

Secretion of pituitary TSH

Question 36

What is goitre?

Answer 36

Thyroid overstimulation by TSH Hypo and hyperthyroid states

Question 37

What are symptoms of hypothyroidism?

Answer 37

Cutaneous edema - increased deposition of CT Goitre Decreased HR, CO and appetite lethargy Low BMR cold intolerance children - intellectual disability and dwarfism

Question 38

What is hypothryoxinaemia?

Answer 38

Low levels of TH production leads to reduced -ve feedback -> increases TSH prod. -> generalized hypertrophy

Question 39

What causes primary hypothyroidism?

Answer 39

Iodine deficiency genetic mutations Toxicity cancers autoimmune diseases

Question 40

What is secondary hypothyroidism?

Answer 40

Abnormality of hypothalamus or pituitary

Question 41

What is the treatment for hypothyroidism?

Answer 41

Replacement theary with levothyroxine Dietry iodine supplementation

Question 42

What are symptoms of hyperthyroidism?

Answer 42

Increased BMR and body temp. Increased sympathetic nerve activity -> increased HR Anxiety Goitre Bulging eyes

Question 43

What is thyrotoxicosis?

Answer 43

Any cause of increased thyroid hormone leading to hypermetabolic rate

Question 44

What can cause thyrotoxicosis?

Answer 44

Overdose of T4 in hypothyroidism Germline or somatic gain of function mutations in TSH receptors

Question 45

What causes hyperthyroidism?

Answer 45

Primary - autoimmune - antibodies to TSH receptor, T3/4 hypersecretion, thyroid adenoma Secondary - excess TSH (pituitary) (adenomas), excess TRH in hypothalamus

Question 46

How does Graves Disease cause goitre?

Answer 46

Autoantibodies directed against TSH receptor - stimulates TH production and hypertrophy of gland Increased feedback inhibition of pituitary TSH production

Question 47

How is hyperthyroidism treated?

Answer 47

Agents that interfere with production of T3 and T4 Destruction of thyroid gland

Question 48

What is Thyroid Storm?

Answer 48

Hypermetabolic state characterized by extreme hyperthyroidism

Question 49

What are symptoms of throid storm?

Answer 49

tachycardia, cardiac arrhythmias, congestive heart failure, pyrexia and dehydration

Question 50

How can thyroid storm be treated?

Answer 50

Beta blockers - reduce sympathetic activation Glucocorticoids (reduce T4 to T3 conversion) Thionamides (inhibit new hormone synthesis)