The Thyroid gland

Question 1

How much does a normal thyroid gland weigh?

Answer 1

15-20g

Question 2

What two hormones does the thyroid gland secrete?

Answer 2

T3 (triiodothyronine) – most active form, receptors have higher affinity for T3

T4 (thyroxine) – most circulates as this

Question 3

Whats the other name for T3?

Answer 3

triiodothyronine

Question 4

What is the other name for T4?

Answer 4

thyroxine

Question 5

Which of the 2 hormones produced by the thyroid is more physiologically active?

Answer 5

Triiodothyronine (receptors have a higher affinity for T3)

Question 6

Which hormone has a higher concentration in serum?

Answer 6

T4

Question 7

What 2 cells are found in the thyroid gland?

Answer 7

C (clear) cells which secrete calcitonin (Ca2+ regulating hormone)

Follicular cells that support thyroid hormone synthesis and surround hollow follicles.

Question 8

Describe the structure and contents of follicles in the thyroid gland

Answer 8

Thyroid follicles are spherical structures whose walls are made of follicular cells. Centre of follicle filled with colloid = sticky glycoprotein matrix. Contain 2-3 months supply of TH.

Question 9

What cells produces the enzymes required to produce the thyroid hormones?

Answer 9

Follicular cells

Question 10

What do the follicular cells produce to aid in thyroid hormone production?

Answer 10

Enzymes responsible for TH production

Thyroglobulin (covered in tyrosine residues for TH production)

Question 11

What enzyme catalyses TH synthesis?

Answer 11

thyroid peroxidase

Question 12

What allows transport of iodine into follicular cells for thyroglobulin production?

Answer 12

Na+/I- transporter symport

The coupling to Na+ (which follows its concentration gradient) enables the follicular cells to take up iodide against its own concentration gradient.

Question 13

How does iodine then enter the colloid from the follicular cells?

Answer 13

(Thyroglobulin with iodine residues is endocytose to the colloid)

Free iodine is then exported via pendrin transporter to the colloid, where it can be ionised and used for TH formation

Question 14

What compounds can inhibit iodine transport into the thyroid gland?

Answer 14

Thiocyanates - compounds formed from detoxification of cyanide. Common origin is cigarette smoke.

Question 15

What transporters release THs into the bloodstream from the follicular cells?

Answer 15

Released from the cells via monocarboxylate transporters into the bloodstream following exocytosis from the colloid after TSH stimulation

Question 16

What plasma proteins bind to TH hormones and why?

Answer 16

Bind to thyroxine-binding globulin, allows transport of lipid soluble hormones

Question 17

What % of T3 and T4 in plasma are protein bound?

Answer 17

99.8%

Question 18

To which TH does thyroxine binding globulin have a higher affinity for, resulting in its longer half life in plasma?

Answer 18

Thyroxine Binding Globulin (TBG) has a particularly high affinity for T4, releasing it only slowly into the plasma. This accounts for the longer half life of T4:

o T4 ~ 6 days
o T3 ~ 1 day

Question 19

What has an inhibitor effect on TSH and TRH?

Answer 19

Free T3 and T4 - negative feedback loop

Question 20

What are the circulating levels of T4 and T3?

Answer 20

Most TH circulates in the form of protein bound T4 ~100nmoles/l, while T3 is only ~2.3nmoles/l
• Note: free TH is in picomolar range (1000x smaller)

Question 21

What % of TH binding to TH receptors is to T3?

Answer 21

90%

Question 22

What converts T4 to T3?

Answer 22

deiodinase

Question 23

What % of T4 is deiodinated to T3 in plasma?

Answer 23

50% (rest is deiodinated within target cells)

Question 24

What stimuli increase TRH release?

Answer 24

Cold
Exercise
Pregnancy

Question 25

What hormones inhibit TSH release?

Answer 25

Glucocorticoids | Somatostatins

Question 26

What are the functions of thyroid hormones?

Answer 26

o Raises metabolic rate and promotes thermogenesis o Increase hepatic gluconeogenesis o Net increase in proteolysis (catabolic) o Net increase in lipolysis o Critical for growth (role in GH signalling) o Required for foetal brain development

Question 27

How does thyroid hormones influence GH signalling?

Answer 27

Stimulates GH receptor signalling to potentiate its effects on growth

Question 28

How are thyroid hormones essential for foetal brain development, and what causes it?

Answer 28

(deficiency = congenital hypothyroidism) TH hormone deficiency can be caused by dietary iodine deficiency in the mother. Leads to cognitive defects in the new-born

Question 29

What can cause congenital hypothyroidism?

Answer 29

Anatomical defect of the thyroid gland Iodine deficiency Inborn error of thyroid metabolism

Question 30

List two causes of hyperthyroidism

Answer 30

Graves disease - common, antibodies mimicking TSH continuously stimulate TH production Thyroid adenoma - rare hormone secreting thyroid cancer

Question 31

List the features of Graves disease

Answer 31

Graves Disease - antibodies produced that mimic TSH and continually activate the thyroid gland. Increased release of TH switches off TSH release from anterior pituitary so [TSH]plasma very low. Thyroid gland may be 2-3x normal size due to hyperplasia (goitre) Hyperactivity of cells also apparent.

Question 32

List the symptoms of hyperthyroidism and why they occur

Answer 32

Increased metabolic rate and heat production = weight loss/ heat intolerance Increased protein catabolism = muscle weakness/weight loss Altered nervous system function = hyperexcitable reflexes and psychological disturbances Elevated cardiovascular function = TH is permissive to epinephrine, β receptors = increased HR/contractile force, high output, cardiac failure

Question 33

List 3 causes of hypothyroidism

Answer 33

Hashimoto’s Disease - autoimmune attack of thyroid gland Deficiency in dietary iodine – only 50mg/year required but many areas of the world soil has insufficient quantities. Main source of dietary iodine was table salt which was enriched with iodine, but no longer in the UK. Milk, fish, seafood and seaweed are good sources. Idiopathic - no known cause, may be linked to thyroiditis

Question 34

List the symptoms of hypothyroidism and why they occur

Answer 34

Decreased metabolic rate and heat production = weight gain/cold intolerance (lost catabolic effect to produce energy) Disrupted protein synthesis = brittle nails/thin skin Altered nervous system function = slow speech, reflexes, fatigue Reduced cardiovascular function = slow heart rate, weaker pulse

Question 35

What is goitre and what causes it?

Answer 35

Thyroid pathologies (hypo- and hyperthyroidism) are often accompanied by significant enlargement of the thyroid gland, which is termed goitre Goitre formation may be caused by: - increased trophic action of TSH on thyroid follicular cells (hypothyroidism) - over-activity as a result of autoimmune disease (Graves Disease) which results in hypertrophy (overgrowth) of thyroid gland

Question 36

How are goitres treated?

Answer 36

Treatment for a goitre can include medication, hormone therapy and surgery (e.g. thyroidectomy). The treatment you receive will depend on: o The size of the goitre o The symptoms the goitre is causing o Whether you have any underlying thyroid condition