The Thyroid Gland

Question 1

What are the two physiologically active forms of thyroid hormones?

Answer 1

T3 - Triiodothyronine

T4 - Thyroxine

Question 2

What are the 2 cell types of cell in the thyroid gland?

What is there function?

Answer 2

1. C (clear) cells which secrete calcitonin (a hormone involved in calcium regulation)
2. Follicular cells which support thyroid hormone synthesis and surround hollow follicles

Question 3

What are thyroid follicles?

Answer 3

Spherical structures filled with colloid

Walls are made of follicular cells

Colloid is a sticky glycoprotein matrix

Contains arund 2-3 months supply of TH

Question 4

How do the follicular cells suport thyroid hormone production?

Answer 4

Manufacture enzymes that make thyroid hormones as well as thyroglobulin

Question 5

What is thyroglobulin?

Answer 5

Large protein

Contains many tyrosine residues

Question 6

How do follicular cell derived enzymes and thyroglobulin enter the collid?

Answer 6

The enzymes and thyroglobulin are packaged into vesicles and exported from the follicular cells into the colloid.

Question 7

What is the role of follicular cells and iodide?

Answer 7

Actively concentrate iodide from the plasma and transport it into the colloid where it combines with the tyrosine residues to form the thyroid hormones

Question 8

Where do iodide and tyrosine come from?

Answer 8

The diet

Question 9

What is the precursor for thyroxine and triiodothyronine?

Answer 9

Both derived from tyrosine

Question 10

What is the enzyme responsible for thyroid hormone synthesis?

Answer 10

Thyroid peroxidase - found on the apical membrane of follicular cells

Question 11

How does iodide travel from the plasma to the colloid?

Answer 11

Iodide enters the follicular cells from the plasma via Na+/I- transport (symport). The coupling enables the follicular cells to take up iodine against a concentation gradient.

Iodide is then transported into the colloid via the pendrine transporter

Question 12

What is the effect of thiocyanates on iodide transport?

Answer 12

Iodide transport into thyroid gland is inhibited by thiocyanates, compounds formed from detoxification of cyanide. Common origin is cigarette smoke.

Question 13

Look

Answer 13

Important to note that both sodium and iodine are transported into the cell

Also thyroglobulin is made in the follicular cell and transported into the colloid

Notice pendrine and sodium/iodide transporter

Question 14

What is the action of thyroid peroxidase?

Answer 14

Catalyses the addition of iodide to tyrosine residues in thyroglobulin

(iodide loses and electron to become iodine)

Question 15

What hormones are made when iodide starts to get added to tyrosine?

Answer 15

Addition of one iodine to tyrosine = MIT (monoiodotyrosine).

Adding a second iodine = DIT (diiodotyrosine).

MIT and DIT then undergo reactions where:

MIT + DIT = triiodothyronine or T3, or

DIT + DIT= tetraiodothyronine or Thyroxine T4.

Question 16

What happens to the colloid in response to TSH?

Answer 16

In response to TSH, portions of the colloid are taken back up into the follicular cell by endocytosis. Within the cells they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release thyroid hormones.

Question 17

What happens once the thyroid hormones are released from thyroglobulin by the proteolytic enzymes?

Answer 17

Both T3 and T4 are lipid soluble and so pass across the follicular cell membrane into the plasma, where they bind to plasma proteins, mainly thyroxine-binding globulin.

Both T3 and T4 circulate in the plasma

Question 18

What releases TSH?

Answer 18

The pituitary

Question 19

If there is no stimulation by TSH, where are the thyroid hormones stored?

Answer 19

Stored within the colloid

Question 20

What proportion of T3 and T4 circulates in the plasma bound to plasma protein?

Answer 20

99.8% §

Question 21

Why does T4 have a longer half life than T3?

Answer 21

T4 half life is - around 6 days

T3 half life is around 1 day

Thyroxine binding has particularly high affininty for T4 releasing it slowly into the plasma

Question 22

What chemical mediators are responsible for the negative feedback on the anterior pituitary and the hypothalamus?

Answer 22

Hypothalamus produces TRH

Anterior pituitary produces TSH

Only free hormone (unbound T4 or T3) exerts an inhibitor effect on TSH and TRH

Question 23

What form of the thyroid hormone is most common?

Answer 23

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 24

Why is the majority (90%) of the TH binding to TH receptors inside cells by T3?

Answer 24

The TH receptor has a much higher affinity for T3 than T4 making T3 3-5 times more physiologically active than T4

Question 25

T4 is deiodinated to T3 by deiodinase enzymes - where does this happen?

Answer 25

Around half the T4 is deiodinated in plasma, the remaining fraction being deiodinated inside target cells The level of deiodinase activity can be altered at different times in different tissues to suit demand.

Question 26

What is responsible for the continuos secretion of thyroid hormone?

Answer 26

As a result of TRH release from the hypothalamus

Question 27

What factors increase the release of thyroid releasing hormone?

Answer 27

Cold, exercise and pregnancy

Question 28

What is the effect of glucocorticoids and somatostatin on TSH?

Answer 28

Glucocorticoids inhibit TSH and conversion of T4 to T3 (iodinase) Somatostatin inhibits TSH

Question 29

What are the receptors for thyroid hormone function?

Answer 29

Nuclear receptors in target cells They change transcription and translation to alter protein synthesis

Question 30

What is the effect on the body of thyroid hormones?

Answer 30

raises metabolic rate and promotes thermogenesis increase hepatic gluconeogenesis net increase in proteolysis net increase in lipolysis critical for growth (lack of TH results in retarded growth) - anabolic - stimulates GH receptor expression (thyroid hormones are permissive to GH) required for foetal brain development (deficiency = congenital hypothyroidism) - can be caused by dietary iodine deficiency in the mother

Question 31

What are the causes of hyperthyroidism?

Answer 31

* Graves Disease - (common) antibodies produced that bind 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. Hyperactivity of cells also apparent. * Thyroid Adenoma - (rare ) hormone-secreting thyroid tumour

Question 32

What are symptoms of hyperthroidism?

Answer 32

1. Increased metabolic rate and heat production - weight loss/ heat intolerance 2. Increased protein catabolism - muscle weakness/weight loss 3. Altered nervous system function - hyperexcitable reflexes and psychological disturbances 4. Elevated cardiovascular function. TH is permissive to epinephrine, b receptors - increased HR/contractile force, high output, cardiac failure

Question 33

What are the 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

What are the symptoms of hypothyroidism?

Answer 34

1. Decreased metabolic rate and heat production - weight gain/cold intolerance 2. Disrupted protein synthesis - brittle nails/thin skin 3. Altered nervous system function - slow speech/reflexes, fatigue 4. Reduced cardiovascular function - slow heart rate/weaker pulse

Question 35

What are goitres?

Answer 35

•Thyroid pathologies (hypo- and hyperthyroidism) are often accompanied by significant enlargement of the thyroid gland

Question 36

What causes the goitre formation?

Answer 36

•Goitre formation may be caused by increased trophic action of TSH on thyroid follicular cells (hypothyroidism) or over-activity as a result of autoimmune disease (Graves Disease) Results in hypertrophy of the thyroid gland Description of diagram: Hypothyroidism (left) - there is not much T4/T3 therefore, the TSH concentration increases in an effort to make more, however T4/T3 cannot be made since there is no iodine and the cycle continues Hyperthyroidism (right) Thyroid stimulating immunoglobulins continuously stimulate the production of T3/T4 by imitating TSH

Question 37

Look

Answer 37

Primary disorder because the gland producing the hormone is not working correctly

Question 38

Look

Answer 38

So hypothyroidism (left) - there is no negative feedback from T3/T4 Hyperthyroidism - Strong negative feedback but it makes no difference - auto antibodies mimic TSH and don't respond to negative feedback Remember Graves will have a low TSH