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year 2 endocrine - Robbie > The Thyroid Gland > Flashcards

The Thyroid Gland Flashcards

1
Q

where is the thyroid gland? and is it big?

A

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

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2
Q

what are the thyroid hormones that the thyroid gland makes?

A

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

T3 (triiodothyronine)

T4 (thyroxine)

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3
Q

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

A
  1. C (clear) cells which secrete calcitonin (Ca2+ regulating hormone)
  2. Follicular cells which support thyroid hormone synthesis and surround hollow follicles
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4
Q

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

A

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)

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5
Q

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 _______

A

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

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6
Q

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

A

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

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7
Q

Where do we get tyrosine and iodide from?

A

Both tyrosine and iodide are derived from the diet

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8
Q

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

A

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

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9
Q

How does iodide become iodine?

A

Iodide oxidised to iodine in the colloid

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10
Q

What is Thyroid peroxidase (aka thyroperoxidase)?

A

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

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11
Q

What does the addition of one iodine to tyrosine make?

A

MIT (monoiodotyrosine)

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12
Q

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

A

DIT (diiodotyrosine)

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13
Q

MIT and DIT then undergo conjugation reactions where:

MIT + DIT = ?????

A

MIT + DIT = triiodothyronine or T3

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14
Q

MIT and DIT then undergo conjugation reactions where:

MIT + DIT = ?????

A

MIT + DIT = triiodothyronine or T3

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15
Q

MIT and DIT then undergo conjugation reactions where:

DIT + DIT = ?????

A

DIT + DIT = tetraiodothyronine or Thyroxine T4

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16
Q

MIT and DIT then undergo conjugation reactions where:

MIT + DIT = triiodothyronine or T3, or

DIT + DIT = tetraiodothyronine or Thyroxine T4

What catalyses these reactions?

A

These reactions are catalysed by thyroid peroxidase

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17
Q

Wat does TSH cause?

A

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

18
Q

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

A

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

19
Q

Both T3 and T4 circulate in the ______

A

Both T3 and T4 circulate in the plasma

20
Q

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 _______

A

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

21
Q

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

A

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

22
Q

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

A

T4, releasing it only slowly into the plasma

23
Q

What is the half life of T3 and T4?

A

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

24
Q

How much TH is free and active?

A

Only 0.2% is free in plasma and physiologically active

25
Q

How is the release of TH stopped?

A

Only free hormone exerts an inhibitor effect on TSH and TRH

Long loop and also a short loop from TSH acting on TRH

26
Q

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))

A

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))

50x more total (free+bound) T4 in plasma than T3

27
Q

90% of TH binding to TH receptors inside cells is T_

A

T3

28
Q

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

A

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

29
Q

T4 is deiodinated to T3 by what?

A

deiodinase enzymes

30
Q

How much T4 is deiodinated?

A

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

31
Q

what things increase secretion of TRH form the hypothalamus?

A

cold

exercise

pregnancy

32
Q

what hormones are inhibitory to TSH?

A
33
Q

TH has a very permissive effect on what?

A

GH

34
Q

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

A

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

35
Q

what is thyroid hormone function?

A

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)

36
Q

what are the causes of hyperthyroidism?

A
  • 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
37
Q

what are the symptoms of hyperthyroidism?

A
  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
38
Q

what are the causes of Hypothyroidism?

A
  • 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
39
Q

what are the symptoms of hypothyroidism?

A
  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
40
Q

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

A

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

41
Q

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

A
42
Q

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

A

Both examples above are primary (1o) disorders of endocrine hormone release (direct effect on endocrine gland producing end hormone)

Secondary (2o) and tertiary (3o) endocrine dysfunction also possible from pituitary and hypothalamic defects respectively. See adrenal lecture.

year 2 endocrine - Robbie (28 decks)

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