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P1: Endo > Thyroid Gland > Flashcards

Thyroid Gland Flashcards

1
Q

What is the developmental function of the thyroid?

A

→ CNS and bone

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2
Q

What is the metabolic function of the thyroid?

A

→ Essential for normal metabolism of many body tissues

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3
Q

What are the 2 main branches that supply the thyroid?

A

→ Inferior thyroid artery - subclavian

→ Superior thyroid artery - carotid

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4
Q

What are the hormonally active thyroid cells?

A

→ Follicular cells

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5
Q

What cells secrete calcitonin and what does it do?

A

→ C cells

→ Reduces plasma calcium

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6
Q

What is thyroid hormone derived from?

A

→ two iodinated tyrosine molecules

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7
Q

What are the two forms of thyroid hormone?

A

→ Tri iodothyronine (T3)

  • active form
  • converted in target cells
  • binds to receptor and exerts its effects

→ Thyroxine T4

  • major form released into blood
  • less active
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8
Q

What is reverse T3?

A

→ Iodinated on a different side

→ Inactive

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9
Q

How does iodide diffuse into the cell?

A

1) uptake of iodide from the circulation via Na+- I- pump on basolateral side
2) iodiode diffuses out into the colloid via a pendrin exchanger
3) At the extracellular apical membrane iodine is oxidized to iodine and bound to tyrosine

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10
Q

What happens to iodide at the apical membrane?

A

1) At the extracellular apical membrane iodine is oxidized to iodine and bound to tyrosine
(this requires thyroid peroxidase and hydrogen peroxidase)

2) T4 and T3 are formed from di or mono iodinated thyroglobulin

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11
Q

How are T3 and T4 brought back into the cell?

A

1) TSH stimulates colloid droplets with thyroid hormones within the thyroglobulin chain are taken back up into the cell via pinocytosis

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12
Q

How is thyroglobulin separated from T3 and T4?

A

→ Colloid droplets fuse with lysosomes causing hydrolysis of thyroglobulin and the release of T3 and T4

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13
Q

How is most of the thyroid hormone found in the circulation?

A

→ Bound to plasma protein

→ mainly thyroid binding globulin

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14
Q

What is the most abundant form of thyroid hormone?

A

→ T4

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15
Q

What is the family of thyroid hormone receptors ?

A

→ Nuclear receptors

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16
Q

What does the thyroid receptor have a higher affinity for?

A

→ High affinity for T3

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17
Q

What does the thyroid receptor activation require?

A

→ Dimerization
→ with another TR or a RXR
Activation requires dimerization with another TR or retinoid X receptor (RXR)​

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18
Q

What genes are thyroid receptors encoded by?

A

→ TR alpha
→ TR beta
Each of the receptors come in two isoforms by alternative splicing​

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19
Q

What do nuclear receptors consist of?

A

→ DNA binding domain
→ Hormone binding domain
→ Transcription factor binding domain

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20
Q

What do D2 enzymes convert?

A

→ T4 into T3

21
Q

What do D3 enzymes do?

A

→ Inactivates T3 by converting it to T2 (inactive)

→ T4 into reverse T3 (inactive)

22
Q

What do you need to make D enzymes?

A

→ Selenium

23
Q

How does thyroid hormone get into cells?

A

Transporters such as MCT8

24
Q

What do mutations in MCT8 gene cause?

A

→ Allan hernon dudley syndrome

→ Associated with psychomotor retardation

25
Q

How does TH increase metabolic rate?

A

→ Increases number and size of mitochondria
→ Enzymes in the metabolic chain
→ Increases Na/K+/ATPase
→ Positive inotropic and chronotropic effects
→ Synergizes with sympathetic nervous system

26
Q

How does TH act on the energy metabolism?

A

→ Antagonizes insulin signalling partially

→ Gluconeogenesis and lipolysis are stimulated

27
Q

How is TH made?

A

→ Parvocellular neurons in hypothalamus release TRH (thyrotrophin releasing hormone) into the median eminence carried by the portal vein to the anterior pituitary

→ TRH stimulates thyrotrophs of the anterior pituitary to secrete TSH

28
Q

What 2 factors stimulate the hypothalamus to produce TH?

A

→ Stress

→ Cold

29
Q

What is an indicator of congenital hypothyroidism ?

A

→ HIGH TSH

30
Q

Why is high TSH and high TRH indicative of HYPOthyroidism?

A

→ If thyroid isn’t producing T3 or T4
→ There is no negative feedback because more needs to be made
→ TRH and TSH concentration are high

31
Q

What does lack of inhibition the equivalent of?

A

→ Stimulation

32
Q

What is the TSH receptor ?

A

→ A GPCR

Main effects mediated via Gs and cAMP

33
Q

What are the main effects of the TSH receptor?

A

→ Iodide uptake
→ transcription of NIS, TG and TPO
→ Stimulates thyroid growth
→ Stimulates the uptake of colloid

34
Q

What is goitre?

A

→ Swelling of the thyroid gland

35
Q

What is euthyroid?

A

→ Normal function

36
Q

What is primary hyperthyroidism?

A

→ Thyroid gland is the problem

37
Q

What is secondary hyperthyroidism?

A

→ Problem in the pituitary

38
Q

What is the diagnosis for low TRH and low TSH but high T4 and T3?

A

→ Primary hyperthyroidism

39
Q

What is the diagnosis for high TRH & TSH but low T4 and T3?

A

→ Primary hypothyroidism

40
Q

What is the diagnosis for low TRH, high TSH and high T4 and T3?

A

→ Secondary hyperthyroidism

41
Q

What is Graves disease?

A

→ Autoimmune
→ High TH
→ Low TSH
→ Primary hyperthyroidism

42
Q

What are the symptoms of Graves disease?

A 
→ weight loss
→ Tachycardia
→ Fatigue
→ Goitre
→ Opthalmopathy
43
Q

What binds to the TSH receptor?

A

→ antibodies stimulate the production of TSH

44
Q

What is Hashimotos disease?

A

→ Autoimmune
→ Low TH
→ High TSH

45
Q

What are symptoms of hashimotos?

A

→ Lethargy
→ Intolerance to cold
→ Lack of growth and development
→ Diffuse goitre

46
Q

What type of cells are present in the thyroid?

A

follicular cells
colloid (mainly thyroblobulin)​
c-cell (parafollicular cell)​

47
Q

Describe the synthesis of TH

A

→Active uptake of I- across basolateral membrane, against concentration and electrical gradient, by Na/I symporter (NIS). Stimulated by TSH.​

→Iodide efflux (diffusion) across apical membrane via exchanger known as pendrin (PDS).​

→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. ​

→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). ​

48
Q

Describe the steps of TH release

A

→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.​

→Fusion of colloid droplets with lysosomes causes hydrolysis of thyroglobulin and release of T3 and T4.​

→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.​

→Secretion probably relies on membrane transporter​

P1: Endo (12 decks)

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