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Endo > Thyroid gland > Flashcards

Thyroid gland Flashcards

1
Q

”
State the development functional of the thyroid gland”

A

“Essential for normal development, especially CNS and bone
“

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2
Q

”
State the metabolic functional of the thyroid gland”

A

“Essential for normal metabolism of many body tissues
“

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3
Q

Describe the blood supply to the thyroid gland?

A

Rich blood supply: More blood per unit weight than kidney

Supplied by:
- Inferior thyroid artery from subclavian
- Superior thyroid artery from carotid
“

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4
Q

State the components of the thyroid gland tissue?

A

“Contains spherical follicular cells

  • These are arranged in a colloid.
  • Apical surfaces come into contant with colloid between follice cells
  • C-cells are also found here”
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5
Q

What is the function of the follicular cells?

A

Syntheisize and secrete TH (thyroid hormones)

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6
Q

What is the function of C-cells?

A

Secrete calcitonin

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7
Q

What are thyroid hormones derived from?

A

Two iodinated tyorisine molecules

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8
Q

State the 2 types of thyroid hormones

A

“T4: major form released to blood, less active (prohormone)
- Needs to become converted into T3 in order to become effective
T3: active form, converted in target cells
“

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9
Q

What hormone stimulates the steps in TH synthesis and release?

A

“Thyrotropin
- Also known as TSH (thyroid stimulating hormone)”

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10
Q

State the steps involved in TH synthesis (4)?

A

“1. Active uptake of I- across basolateral membrane,

  • Against concentration and electrical gradient, by Na/I symporter (NIS).
  • Stimulated by TSH.
  1. Iodide efflux (diffusion) across apical membrane via exchanger known as pendrin (PDS).
  2. At extracellular apical membrane iodide is oxidized to iodine and covalently bound to tyrosine residues within the thyroglobulin (TG) macromolecule.
    - Requires thyroid peroxidase (TPO) and H2O2.
  3. Tyrosine residues may be iodinated in one (mono-iodotyrosine, MIT) or two (DIT) positions.
    - Coupling of iodotyrosine residues (catalysed by TPO) produces T4 (DIT-DIT) and a smaller amount of T3 (MIT-DIT).
    “
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11
Q

State the steps involved in TH release (4)?

A

“5. Under the influence of TSH, colloid droplets consisting of thyroid hormones within the thyroglobulin molecules are taken back up into the follicular cells by pinocytosis.

  1. Fusion of colloid droplets with lysosomes causes hydrolysis of thyroglobulin and release of T3 and T4.
  2. About 10% of T4 undergoes mono- deiodination to T3 before it is secreted.
    - The released iodide is reutilized.
    Several-fold more iodide is reused than is taken from the blood each day but in states of iodide excess there is loss from the thyroid.
  3. Approximately 100 μg TH secreted per day (90% T4 and about 10% T3).
    Secretion probably relies on membrane transporter
    “
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12
Q

State with %, what circulating thyroid hormones can be bound to?

A

”- Over 99% bound to plasma protein
- Mainly thyroid-binding globulin (~70%)
- also transthyretin (10-20%)
- Albumin (10-20%)
“

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13
Q

What superfamily does TH receptors (TR) belong to?

A

Nuclear receptor superfamily
- Specifically are a ligand-activated/hormone responsive nuclear TF

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14
Q

Which TH hormone does TH receptors have high affinity for?

A

T3

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15
Q

What does activation of TH receptors require?

A

Activation requires dimerization with another TR or retinoid X receptor (RXR)

TR= TH receptor

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16
Q

State the 2 genes which encode for the 2 types of TRs?

A

TR alpha and TR beta (these are the 2 types of TRs
- Expression of alpha precedes beta in all species

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17
Q

State the general structure with function of TH receptors?

A

A/B, DNA and hormone region

A/B= N terminus region - Transactivation domain (transcriptional activity)
DNA= DNA binding domain (binds to promotor DNA)
Hormone= Ligand binding domain - where dimerization occurs
18
Q

What must be present for transcription to be induced for a TH
receptor?

A

Presence of ligand binding activates transcription

19
Q

What controls the relative levels of THs?

A

Relative levels of T3, T4 and inactive forms controlled in target tissues by
- Three iodothyronine selenodeiodinases, D1-3

20
Q

Describe the role of D1-3?

A

Family of three enzymes (deiodinases) that activate or inactivate TH.

Tissue-specific expression of these enzymes can regulate the amount of T3 actually available to bind with receptor at the target tissues.

21
Q

What is essential in the diet for production of D1-3?

A

trace element selenium

22
Q

State the difference in action between D2 and D3.

A

D2 increases T3 -> Increases TH action
D3 decreases T3 -> Decreases TH action

23
Q

State the inactive metabolite forms of T3/T4

A

T2, rT3

24
Q

What are required for THs to diffuse across cell membrane
and state examples?

A

Transporters are required
- , e.g., MCT8, OATP1C1

FC:
THs are not lipophilic enough to diffuse freely across cell membrane

25
Q

What can mutations in MCT8 result?

A

Can cause an X-linked condition -> Allan–Herndon–Dudley syndrome
- Associated with psychomotor retardation

26
Q

State the 3 major functions of THs?

A

Increases metabolic rate
Energy metabolism
Growth and development

27
Q

How does TH increase metabolic rate?

A

Number and size of mitochondria, enzymes in metabolic chain, Na/K ATPase activity
Positive inotropic and chronotropic effects on heart
Synergizes with sympathetic nervous system

28
Q

How does TH affect energy metabolism?

A

Partially antagonizes insulin signalling
Gluconeogenesis, lipolysis

FC:
Generally favouring increased energy expenditure.

29
Q

What is the hypothalamic-pituitary-thyroid axis

A

Negative feedback control of thyroid hormone synthesis and secretion
- via the hypothalamo-pituitary axis

30
Q

Describe the pathway of the hypothalamic-pituitary-thyroid axis?

A
  1. , Hypothalamic neurosecretory cells release thyrotrophin-releasing hormone (TRH) into the portal capillaries.
  2. TRH stimulates thyrotrophs of anterior pituitary to secrete thyroid stimulating hormone (TSH) to the thyroid gland.
31
Q

What factors affect TH set point?

A

Stress
Cold

Both increase TH

32
Q

Draw or describe the -ve feedback control of TH synthesis

A
33
Q

How are the main effects from the TSH receptor mediated?

A

Main effects mediated via Gs and cAMP – PKA cascade
- As its a GPCR

34
Q

State the 4 actions of TSH?

A
  • Increases iodine uptake
  • Stimulates other reactions involved in TH synthesis (e.g., TPO)
  • Stimulates uptake of colloid
  • Induces growth of thyroid gland (which can lead to goitre)
35
Q

State what the following status of the throyid gland mean?
Euthyroid
Hyperthyroidism
Hypothyroidism

A

Euthyroid: normal thyroid function
Hyperthyroidism: TH excess
Hypothyroidism: TH deficiency

36
Q

State the primary and secondary problem that causes hyperthyroidism?

A

Primary: problem is thyroid gland itself
Secondary: problem is pituitary regulation

37
Q

State how -ve feedback affects system in these TH status

  • Primary hyperthyrodism
  • Primary hypothyrodisim
  • Secondary hyperthyrodisim
A

PH: Higher T4/T3 -> Lower TRH + TSH
PHO: Lower T4/T3 -> Higher TRH + TSH
SH: Higher T3/T4 - Lower TRH + Higher TSH
- in SHO, Pituitary regulation is impared so affects TSH

38
Q

What diseases can primary hyperthyrodisim and hypothyroidism cause?

A 
Hyper= Graves disease
Hypo= Hashimoto's
39
Q

Describe 5 features of grave’s disease?

A

Grave’s disease is caused by primary hyperthyrodiism

Autoimmune
High circulating TH, low TSH
Weight loss, tachycardia, fatigue
Diffuse goitre ( due to TSH receptor stimulation) - swelling of the neck
due to enlarged thyroid gland
Opthalmopathy (Thyroid eye disease)

40
Q

How does diffuse goitre occur in grave’s disease even though low TSH?

A

Occurs due to auto-antibodies binding to TSH receptor

  • Stimulates TH synthesis
  • Unregulated production of TH

FC:

Diffuse goitre is swelling of the neck due to enlarged thyroid gland

41
Q

Describe 5 features of hashimoto’s?

A

Hashimoto’s: primary hypothyroidism

Autoimmune
Low circulating TH, high TSH
Lethargy, intolerance to cold
Lack of growth and development
Diffuse goitre (swelling of the neck
due to enlarged thyroid gland)

42
Q
A

Endo (9 decks)

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