Thyroid Flashcards

1
Q

What is the general structure of a thyroid hormone (thyroxine) molecule?

A

An amino acid attached to an inner and an outer ring structure which are connected by an ether link. Each ring holds 2 iodine atoms and the outer ring holds one hydroxy group as well.

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2
Q

How is T4 altered to produce T3 (the active nuclear hormone)?

A

It is deiodinated.

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3
Q

How can radioactive iodine make its way into the human body?

A

Ingestion or inhalation. Easily dissolved in water so moves through atmosphere and into organisms freely.

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4
Q

How can radioactive iodine be used in medicine?

A

Low dose: treat overactive thyroid

High dose: treat thyroid cancer

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5
Q

What are the 4 main effects of thyroid hormone activity?

A
  1. Normal fetal/child development (esp. brain)
  2. Maintain basal metabolic rate
  3. Manage cardiovascular system
  4. Modulate other hormones’ functions
    (+ many others not required to know!)
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6
Q

Which category of endocrine disease is the most common? Does it affect one gender more strongly than the other?

A

Thyroid hormone diseases are the most common and disproportionately affect women.

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7
Q

What differentiates hypothyroidism from hyperthyroidism?

A

Hypothyroidism: low levels of TH
Hyperthyroidism: high levels of TH
(complex connection with estrogen)

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8
Q

What is the current trend for incidences of thyroid disease in North America? What is a possible explanation for this?

A

Thyroid disease is on the rise, maybe due to increased use of endocrine disrupting compounds and molecules which mimic thyroid hormone structure.

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9
Q

What structures make up the thyroid gland?

A

Many colloid-filled sacs called follicles which have capillaries to allow thyroid hormone to be released into the blood.

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10
Q

What is the precursor to thyroid hormone? What converts this into thyroxine?

A

A large protein called thyroglobulin. Converted into thyroxine by thyroid peroxidase.

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11
Q

How does thyroid peroxidase help convert thyroglobulin into thyroxine?

A

By adding iodine to 2 tyrosine residues on the protein, then connecting them by forming an ether linkage. The protein chain is degraded, releasing only thyroxine into the blood.

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12
Q

What 10 steps outline the synthesis of thyroid hormone to its release into the bloodstream?

A
  1. Uptake of iodide (active transport)
  2. Uptake of amino acids, sugars
  3. Production of thyroglobulin (TG)
  4. Packaging of TG in Golgi
  5. Secretion of TG into colloid
  6. Add iodine to TG
  7. Storage in colloid until needed
  8. Reabsorption of TG
  9. TG digested
  10. Thyroxine released into blood
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13
Q

What stimulates the reabsorption of thyroglobulin from the colloid and its conversion into thyroid hormone?

A

Thyroid stimulating hormone.

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14
Q

How do people in North America consume the majority of the iodide needed for biological function?

A

As iodized salt (iodide added to salt).

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15
Q

What causes goitre?

A

Lack of iodine, and therefore no production of thyroid hormone. No negative feedback and so thyroid stimulating hormone keeps upregulating the thyroid gland, causing enlargement.

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16
Q

What occurs to thyroid hormone when there is an excess of iodide?

A

Thyroid hormone synthesis is downregulated.

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17
Q

What is the name of the process in which an iodine is removed from the outer ring of thyroxine (T4)? What enzyme does this? What is the result?

A

“Step up” done by 5’-Deiodinase. Results in T3, the most active form of thyroid hormone.

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18
Q

What is the name of the process in which an iodine is removed from the inner ring of thyroxine (T4)? What enzyme does this?

A

“Step down” done by 5-Deiodinase. Results in reverse T3 (T3r), which is inactive in the nucleus.

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19
Q

What differentiates the effects of T3 from the other thyroid hormones (T4, T3r, etc.)?

A

T3 is active in the nucleus and can affect transcription, while the other thyroid hormones have mostly non-genomic effects.

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20
Q

Why are deiodinases important for physiological functions?

A

Allow local tissue modulation of thyroid hormone, so that effects can be altered.

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21
Q

How is thyroxine (T4) metabolized and/or deactivated?

A

Mostly by deiodination to T3 and T3r, but some is also deactivated in the liver and kidney (sulfation, etc).

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22
Q

What is a thyrotroph?

A

A small portion of the anterior pituitary cells which release thyroid stimulating hormone.

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23
Q

How are thyrotrophs stimulated to release thyroid stimulating hormone? How are they inhibited?

A

Stimulated by thyrotropin-releasing hormone and inhibited by somatostatin (both from hypothalamus). Also inhibited by negative feedback from thyroid hormone.

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24
Q

What can cause the hypothalamus to secrete thyrotropin-releasing hormone?

A

Inputs from the circadian rythm or from environmental factors (exposure to cold).

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25
Q

What effects can glucocorticoids and chronic illness have on thyroid hormone production?

A

They both inhibit thyroid stimulating hormone, therefore inhibiting thyroid hormone production.

26
Q

How does thyroid stimulating hormone affect the thyroid gland?

A

Stimulates thyroid hormone synthesis and secretion, but also stimulates follicle growth!

27
Q

Is thyroid hormone hydrophobic or hydrophilic? How does it move through the blood?

A

Hydrophobic, so needs a blood binding protein (thyroid-binding globulin) for movement. This also acts as a large reservoir of circulating thyroid hormone.

28
Q

What is the result of having a deficiency in thyroid-binding globulin?

A

Since it isn’t stabilized, thyroid hormone is mostly degraded, results in hypothyroidism.

29
Q

What is the half-life of bound thyroid hormone in plasma?

A

1 week.

30
Q

What kind of transport is employed to move thyroid hormone into the cell? What about into the nucleus?

A

Mostly active transport through the membrane into the cytoplasm, diffusion into nucleus.

31
Q

How does thyroid hormone move around the cytoplasm?

A

Bound to cytoplasmic thyroid hormone binding proteins with varying affinities.

32
Q

What is the major difference between nuclear thyroid receptors and nuclear steroid receptors?

A

Thyroid receptors stay bound to DNA and do not use heat shock proteins (while steroid receptors do).

33
Q

How is hormone response element specificity established?

A

Through timing of ligand binding, context (cell type, surroundings), cofactor expression, spacing, and DNA sequence.

34
Q

Why does increasing T3 stimulate both proliferation and apoptosis?

A

Because control over replication is integral for growth and avoiding cancer. Must be kept in balance.

35
Q

How does T3 cause increased proliferation as well as apoptosis?

A

By upregulating transcription of cyclins (cyclin D) and caspases (caspase 3).

36
Q

What 2 main genes are implicated in proper thyroid effects?

A

The ones which cause expression of thyroid receptor alpha and thyroid receptor beta.

37
Q

Which type of thyroid receptor autoregulates? What effect does this have on the other type of receptor?

A

Thyroid receptor beta autoregulates, which can upregulate thyroid receptor alpha and amplify effects.

38
Q

How do non-genomic and genomic thyroid hormone effects differ?

A

Non-genomic are faster, take advantage of signal transduction, and have small effects. Genomic are slow, only affect transcription, and have far-reaching effects.

39
Q

What are some examples of non-genomic thyroid hormone effects?

A

Ion flux, mitochondria activity, glucose/AA uptake, actin polymerization, translation efficiency, etc.

40
Q

What effects can T3 have on cardiomyocytes?

A

Genomic: increase muscle strength

Non-genomic: increase HR by acting on membrane receptors

41
Q

In what way can T3 and T4 have a non-genomic effect on cell function?

A

By binding to integrin on cell surface to initiate the MAPK pathway or phosphorylate nuclear thyroid receptors. Can also cause ion flux leading to same result (phosphorylation).

42
Q

What specific mechanistic step is initiated by the phosphorylation of thyroid receptors?

A

The dissociation of co-repressors which can promote transcription via a genomic effect.

43
Q

What is cretinism?

A

Hypothyroidism in a developing child, causing delayed (or permanent loss of) development of body and brain.

44
Q

What are some likely causes of cretinism?

A

Antibodies from the mother which act against thyroid stimulating hormone receptors in child, a severe iodine deficiency, or a thyroid axis defect.

45
Q

How can infants be screened for cretinism (hypothyroidism during development)?

A

With a neonatal heel pinprick to test the blood.

46
Q

At what point do the effects of fetal hypothyroidism become irreversible?

A

After the second trimester.

47
Q

What is the major source of thyroid hormone in the developing fetus?

A

Maternal thyroid hormone transferred across the placenta (which contains deiodinases).

48
Q

How does pregnancy affect the thyroid gland?

A

Puts increased stress on the thyroid gland. Harmless mostly, but can cause problems in females with subclinical hypothyroidism.

49
Q

At what point during development does thyroid hormone have the biggest effect?

A

The terminal stages of brain differentiation (growth of dendrites/axons, synaptogenesis, myelination, etc.).

50
Q

What is the most common preventable cause of mental disability in the world?

A

Iodine deficiency. Does not just affect humans, but many animal populations as well.

51
Q

What is the most common cause of hypothyroidism? Describe.

A

Hashimoto’s thyroiditis. An autoimmune disease in which the thyroid gland is attacked by lymphocytes.

52
Q

What is a common early symptom of Hashimoto’s thyroiditis?

A

Weight gain despite normal eating.

53
Q

What are 6 common symptoms of hypothyroidism?

A
  1. Lethargy
  2. Generalized weakness
  3. Menstrual irregularity
  4. Cold intolerance
  5. Weight gain
  6. Depression (important)
54
Q

What is the most common cause of hyperthyroidism? Describe.

A

Grave’s disease, an autoimmune disorder causing stimulation of the thyroid.

55
Q

What are the most obvious symptoms of Grave’s disease?

A

Bulging eyes and goitre.

56
Q

What are the 4 highlighted symptoms of Grave’s disease?

A
  1. Cardiac arrhythmia
  2. Weight loss despite increased appetite
  3. Profuse sweating
  4. Bulging eyes
57
Q

What term is used to describe life-threatening hyperthyroidism?

A

THYROID STORM.

58
Q

What type of thyroid issue are cats most likely to suffer? What about dogs? What likely causes these?

A

Cats: hyperthyroidism, usually caused by tumour-enlarged thyroid glands
Dogs: hypothyroidism, caused by autoimmune destruction of thyroid gland

59
Q

Why would frogs be used in studies regarding thyroid function?

A

Homology with humans (same tumour suppressors), “sentinel species”, good lab model because of easy manipulation.

60
Q

How is metamorphosis triggered in tadpoles?

A

By gradually upregulating thyroid hormone (too much at one time can be fatal).

61
Q

What 3 endocrine disrupting compounds were mentioned in relation to thyroid control?

A
  1. Triclosan (an antibacterial agent)
  2. Polybrominated diphenyl ethers (flame retardants)
  3. Plasticizers (ex: bisphenol-A)