The Thyroid Gland COPY

Question 1

where is the thyroid gland? and is it big?

Answer 1

C5-T1

Thyroid gland, shaped like a butterfly, lies across trachea at base of larynx

one of larger endocrine glands, (15-20g), but neither visible nor palpable in health

Question 2

what are the thyroid hormones that the thyroid gland makes?

Answer 2

Synthesises the Thyroid Hormones of which there are two physiologically active forms:

T3 (triiodothyronine)

T4 (thyroxine)

Question 3

what are the 2 types of cells found in the thyroid gland? and their function?

Answer 3

1. C (clear) cells which secrete calcitonin (Ca2+ regulating hormone)
2. Follicular cells which support thyroid hormone synthesis and surround hollow follicles

Question 4

what is a thyroid follicle and what is it made up of?

Answer 4

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 (in precursor form of T3 and T4)

Question 5

Follicular cells manufacture the _______ that make _______ hormones as well as ________, a large protein rich in tyrosine residues

The enzymes and thyroglobulin are packaged into ________ and exported from the follicular cells into the _______

Answer 5

Follicular cells manufacture the enzymes that make thyroid hormones as well as thyroglobulin, a large protein rich in tyrosine residues

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

Question 6

What do the follicular cells also actively concentrate and what is its use?

Answer 6

Follicular cells also 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 7

Where do we get tyrosine and iodide from?

Answer 7

Both tyrosine and iodide are derived from the diet

Question 8

how does iodide enter follicular cells? and then into colloid?

Answer 8

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

Iodide is then transported into the colloid via the pendrin transporter

Question 9

How does iodide become iodine?

Answer 9

Iodide oxidised to iodine in the colloid

Question 10

What is Thyroid peroxidase (aka thyroperoxidase)?

Answer 10

Enzymes exocytosed into the colloid, along with the thyroglobulin, catalyses the oxidation of iodide to iodine and the addition of iodine to tyrosine residues on the thyroglobulin molecule

Question 11

What does the addition of one iodine to tyrosine make?

Answer 11

MIT (monoiodotyrosine)

Question 12

what does adding a second iodine to a tyrosine lead to?

Answer 12

DIT (diiodotyrosine)

Question 13

MIT and DIT then undergo conjugation reactions where:

MIT + DIT = ?????

Answer 13

MIT + DIT = triiodothyronine or T3

Question 14

MIT and DIT then undergo conjugation reactions where:

MIT + DIT = ?????

Answer 14

MIT + DIT = triiodothyronine or T3

Question 15

MIT and DIT then undergo conjugation reactions where:

DIT + DIT = ?????

Answer 15

DIT + DIT = tetraiodothyronine or Thyroxine T4

Question 16

MIT and DIT then undergo conjugation reactions where:

MIT + DIT = triiodothyronine or T3, or

DIT + DIT = tetraiodothyronine or Thyroxine T4

What catalyses these reactions?

Answer 16

These reactions are catalysed by thyroid peroxidase

Question 17

Wat does TSH cause?

Answer 17

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 18

How do T3 and T4 get into the plasma and how are they transported in the blood?

Answer 18

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

Transporter proteins may also be involved in this process as rare mutations in this protein cause major disruption to TH balance

Question 19

Both T3 and T4 circulate in the ______

Answer 19

Both T3 and T4 circulate in the plasma

Question 20

Movement of TH from colloid to plasma is under the influence of ___ released from the ________. ___ stimulates the _________ cells to endocytose colloidal ____________. When not stimulated, the thyroid hormones are stored in the _______

Answer 20

Movement of TH from colloid to plasma is under the influence of TSH released from the pituitary. TSH stimulates the follicular cells to endocytose colloidal thyroglobulin. When not stimulated, the thyroid hormones are stored in the colloid

Question 21

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

Answer 21

More than 99.8% of T3 and T4 circulates in plasma bound to plasma protein

Question 22

Does Thyroxine Binding Globulin (TBG) has particularly high affinity for T3 or T4 and what does this result in?

Answer 22

T4, releasing it only slowly into the plasma

Question 23

What is the half life of T3 and T4?

Answer 23

T4 ~ 6 days; T3 ~ 1 day

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

Question 24

How much TH is free and active?

Answer 24

Only 0.2% is free in plasma and physiologically active

Question 25

How is the release of TH stopped?

Answer 25

Only free hormone exerts an inhibitor effect on TSH and TRH Long loop and also a short loop from TSH acting on TRH

Question 26

Most TH circulates in the form of protein bound T\_ ~100nmoles/l, while T\_ is only ~2.3nmoles/l (note: free TH is in picomolar range (1000x smaller))

Answer 26

Most TH circulates in the form of protein bound T**4** ~100nmoles/l, while T**3** is only ~2.3nmoles/l (note: free TH is in picomolar range (1000x smaller)) 50x more total (free+bound) T4 in plasma than T3

Question 27

90% of TH binding to TH receptors inside cells is T\_

Answer 27

T3

Question 28

Why is 90% of TH binding to TH receptors inside of cells T3?

Answer 28

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

Question 29

T4 is deiodinated to T3 by what?

Answer 29

deiodinase enzymes

Question 30

How much T4 is deiodinated?

Answer 30

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 31

what things increase secretion of TRH form the hypothalamus?

Answer 31

cold exercise pregnancy

Question 32

what hormones are inhibitory to TSH?

Answer 32

Question 33

TH has a very permissive effect on what?

Answer 33

GH

Question 34

What receptors do TH bind to and what effect does this have?

Answer 34

TH bind to nuclear receptors in target cells, where they change transcription and translation to alter protein synthesis

Question 35

what is thyroid hormone function?

Answer 35

raises metabolic rate and promotes thermogenesis, typically through promoting futile cycles of simultaneous catabolism and anabolism increase hepatic gluconeogenesis, although no effect on BG providing pancreas is releasing adequate insulin (therefore not a counter regulatory hormone) net increase in proteolysis net increase in lipolysis critical for growth (lack of TH results in retarded growth) - stimulates GH receptor expression essential for brain development in utero (maternal iodine deficiency = congenital hypothyroidism)

Question 36

what are the causes of hyperthyroidism?

Answer 36

* 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 37

what are the symptoms of hyperthyroidism?

Answer 37

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 38

what are the causes of Hypothyroidism?

Answer 38

* 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 39

what are the symptoms of hypothyroidism?

Answer 39

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 40

does hypo- or hyperthyroidism cause enlargement of the thyroid gland?

Answer 40

Both hypo- and hyperthyroidism are often accompanied by significant enlargement of the thyroid gland Termed goitre 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 (overgrowth) of thyroid gland

Question 41

flow charts showing hypothyroidism due to low iodine and hyperthyroidism due to graves disease

Answer 41

Question 42

hypothyroidism due ot low iodine and hyperthyriodsisn are both what type of disorders and what are other types of disorders that may happen?

Answer 42

Both examples above are primary (1^o) disorders of endocrine hormone release (direct effect on endocrine gland producing end hormone) Secondary (2^o) and tertiary (3^o) endocrine dysfunction also possible from pituitary and hypothalamic defects respectively. See adrenal lecture.