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Metabolic endocrinology 2 > Thyroid gland > Flashcards

Thyroid gland Flashcards

1
Q

What are the functional units of the Thyroid gland? What is the general anatomy of the functioning units?

A

Thyroid Follicles, consisting of a single layer of epithelial cells surrounding a lumen filled with colloid.

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2
Q

What physical changes happen to the functional unit of the thyroid when hyper- or hypo- active?

A

Under-active: thinning of the epithelial cell wall

overactive: hypertrophy of the epithelial cells

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3
Q

How is blood flow regulated to the thyroid gland?

A

Postganglionic sympathetic nerves control the blood flow through the gland.

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4
Q

Why is a properly regulated blood flow important for normal functioning of the thyroid gland?

A

Blood flow controls the release of T3 and T4 hormones. This is done by affecting the flow of delivery of TSH, iodine and nutrients.

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5
Q

What are the 6 steps for the formation of thyroid hormones?

A
  1. Na+/I- symporter transports 2 Na and 1 I- across the membrane of follicular cells. I- is moving against its concentration gradient –> active transport
    I- is moved across the inner membrane into the colloid
  2. Thyroid peroxidase does 2 things: oxidizes I- into its more reactive form and catalyses the iodination of thyroid globulin at its tyrosil residues (that was made and secreted into the colloid by the ER) This forms MIT (T1) and DIT (T2)
  3. the iodotyrosines are linked within the thyroiglobulin to form T3 and T4
    TSH will stimulate endocytosis of the coupled thyrogobulin.
  4. Proteolysis occurs by lysosomes to free the T3 and T4 which diffuse into the blood stream.
  5. iodotyrosines are deiodized to recycle I
  6. T3 and T4 broken down by intrathyroidal 5’-deiodination
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6
Q

What are the names of the first 3 steps of T3/T4 production?

A

Trapping: getting iodine in
Organification: iodination of thyroglobulin
Coupling: linking to form T3 and T4

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7
Q

TSH affects specific steps in the formation of T3 and T4, what are they?

A

increased trapping, iodination, coupling
Causes endocytosis of colloid and proteolysis of thyroglobulin
Stimulates transcription/translation for thyroglobulin

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8
Q

Explain the functioning of the NA+/I- symporter.

A

iodine is transported across the membrane against its gradient by the use the the gradient of Na.
The Na gradient is maintained by the Na+/K+ pump that uses ATP.

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9
Q

What are inhibitory anions for the thyroid?

A

The are anions that limit the uptake of iodine which limit the functioning of the thyroid.

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10
Q

What are the common inhibitory anions and how do they work?

A

ClO4- : blocks the uptake of iodine

Br- and NO2- : competitive inhibition, are present in the diet.

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11
Q

What is radioactive iodine used for? Why?

A

destroy thyroid tissue, for cancer or hyperthyroidism. It is used before surgery

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12
Q

What substance is recommended for use in a nuclear emergency? Why? How does it work?

A

Potassium Iodide
Nuclear emergency can cause overexposure to radioactive iodine which, when taken up, can cause tissue damage.
Saturating the thyroid with not radioactive iodine.

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13
Q

Describe the organification process.

A

Organification: the iodination of thyroglobulin

Thyroperoxidase + Iodine + thyroglobulin-protein with H2O2 –> I-TPO.TG-protein complex

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14
Q

What is a common target for many drugs designed to reduce thyroid production? What is a common consequence?

A

Thyroperoxidase

blocking iodination can lead to increase in TSH production –> hyperplasia and goiter

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15
Q

Where are the tyosines that are most likely iodinated?

A

On the surface of thyroglobulin

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16
Q

What are the precursors to T3 and T4?

A

MIT + DIT= T3
DIT + DIT= T4

MIT=monoiodotyrosine
DIT=diiodotyrosine

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17
Q

Which happens first? iodination or coupling?

A

They occur siultaneously

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18
Q

True or False. There is a positive correlation between the concentration of T3 hormone and concentration of iodine in the blood.

A

False. T3 makes a plateau, kept steady by kinetics?

T4 is positively correlated

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19
Q

Thyroglobulin is synthesized by what? Does the same structure performs the exocytosis into the lumen?

A

Synthesized by rough ER
Golgi sends it into lumen
ER –> vesicle –> golgi –> vesicle –> lumen

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20
Q

What biochemical markers show evidence of sick euthyroid syndrome?

A

high levels of rT3, low T3

hypothyroidism because of another illness, not a problem with the thyroid itself

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21
Q

True or False. Thyroid hormones are lipophilic.

A

True

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22
Q

What carrier proteins are used to transport T3 and T4?

A

Thyroxine binding globulin (TBG)
Transthyretin (thyroxine-binding prealbumen, TBPA)
Albumin

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23
Q

How can certain drugs increase free T3 and T4? What are the side effects? Example drugs?

A

competing with the carrier protein
may lead to hyperthyroidism
epilepsy and inflammation drugs

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24
Q

Which is more active T3 or T4? Which is more abundant?

A

T3 is 2 to 10 times more active
Total T3 is only about 2%, there is about 30% of total T hormones being T3 since receptors have a stronger binding with T4

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25
Q

Why is the Free hormone form important? (without the carrier protein)

A

Because cells cannot take up the bound form

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26
Q

What is the relationship between free hormone and the level of binding protein?

A

the level of binding determines the amount of free hormone
if binding is high, then you need a greater amount of total hormone to maintain the free hormone concentration
if binding is low, you need less

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27
Q

In what situation would protein binding capacity be high? low?

A

high: pregnancy, oral contraceptives
Low: starvation, liver disease

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28
Q

Free hormone, unlike bound hormone, controls certain metabolic processes, name 4?

A

feedback control
tissue action
hormone metabolism
excretion

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29
Q

What effect does starvation have on binding protein? On total hormone needed?

A

decreased binding protein which means:

less required total hormone to maintain free hormone

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30
Q

Where does deiodination occur? What is it?

A

various tissues of the body depending on the type of deiodination
deiodination is the removal of an iodine atom from the hormone which can either activate or inactivate. Removing the atome from the outer ring activates (T4 –> T3)
Removing from the inner ring disactivates (T4–>rT3)

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31
Q

Where are the Type I deidodinase? T4 is converted to what?

A

liver, kindey, muscle, peripheral conversion

T3 (bioactivation, outer ring)

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32
Q

Where are the Type II deiodinase? T4 is converted to what?

A

Brain, pituitary
T3 (bioactivation, outer ring)
Key for feedback on TRH and TSH

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33
Q

Where are the Type III deiodinase? T4 is converted to what?

A

rT3 (inactive form)

34
Q

All three deiodinase contain a rare structural component, what is it?

A

amino acid containing selenium (selenocysteine) in their catalytic center

35
Q

What type of protein are the deiodinases?

A

dimeric integral membrane protein

36
Q

What are three functions of deiodinases?

A

permit local tissue and cell modulation of thyroid hormone
help for adaptation (i.e. iodine deficiency or chronic illness (D3 increase in hyperthyroidism, decrease hypo)
regulate the action of thyroid hormones in early development

37
Q

True or False. Less than 50% of T4 is metabolized through deiodination. The rest is processed by the liver by glucuronidation and biliary secretion.

A

False. around 80% by deiodination

38
Q

What 2 general functions doe thyroid hormones possess and by what means are they accomplished?

A

Growth and development + Maintenance of BMR

Gene transcription

39
Q

True or False. Thyroid hormone receptor are heterodimers.

A

False. They can be monomers, homodimers or heterodimers

40
Q

What 2 genes code for thyroid hormone receptors?

A

erbA and erbB, each gives rise to 2 receptor proteins by alternative splicing.

41
Q

What 4 receptors are there?

A

THRalpha1: Widely distributed
THRalpha2: inhibitor
THRbeta1: widely distributed
THRbeta2: anterior pituitary and specific brain regions

42
Q

How do class 2 receptors work?

A

Class 2 receptors are already bound to the DNA. Binding of T3 causes the release of the corepressor complex. This allows the coactivator complex to attach and stimulate gene transcription.

43
Q

How do thyroid hormones help stimulate thermogenesis?

A

T3 deactivated by D3 –> rT3 –> T2 –> cytochrome C –> increased oxidative phosphorylation
T4 activated by D2 –> T3 –> increase mitochondria transcription
Same T3 –> bind to uncoupling proteins to increase heat production (nucleus)

44
Q

Where are the receptors located in the cell?

A

Membrane (g protein couled receptor) or on nucleus membrane

45
Q

What physiological effects do thyroid hormones have?

A

stimulate lipolysis, increase protein breakdown, promote normal growth, bone dev., brain dev., increase carb absorption, stimulate O2 consumption by cells and increase strength of heart beat

46
Q

Describe the calorigenic response of T4.

A

Leads to an increase in O2 consumption by metabolically active tissues EXCEPT adult brain, testes, uterus, lymph nodes, spleen and anterior pituitary. The response can be due to fatty acid mobilization and increase of Na+/K+ ATPase activity

47
Q

Which of the 2 thyroid hormones has the most significant calorigenic response per dose?

A

T3

48
Q

Describe the kinetics of the response to a single dose of T4.

A

There is a measurable effect in several hours that lasts for 6 days or more.

49
Q

Aside from increased O2 consumption and heat production, what other effects are there to the calorigenic properties of thyroid hormones?

A
  • Increased nitrogen excretion (less muscle)
  • Catabolism of fat/protein (weight loss)
  • Positive nitrogen balance in CHILDREN (growth)
  • Increased vitamin needs
  • conversion of carotene to vitamin A in liver (carotenemia –> yeloowish)
  • increased erythropoiesis (more O2 needs)
  • promote gut motility
50
Q

What can happen with a lack of T4?

A

myxedema –> puffiness of the skin because the proteins and/or mucosaccharides are not being degraded

51
Q

The rise in body temperature due to thyroid hormones can have an what effect on the heart?

A

Activate heat dissipation mechanisms:

  • cutaneous vasodilation: less resistance to peripheral blood flow and more renal Na+ and H2O resorption to increase blood volume –> water retains heat and brings to skin surface
  • increase cardiac output by T3/T4 and catecholamines shorten circulation time of blood by increasing pressure and cardiac rate
52
Q

Why do heart myocytes respond to T3 from circulation and not T4? What effect does it have on the heart?

A

they lack the deiodinase enzyme to form T3

increased heart rate and force of contraction

53
Q

What hormone stimulates heart myocytes? Which genes are turned on, which are inhibited? What roles do the genes have?

A

T3

on: alpha-myosin heavy chain - sarcoplasmic reticulum Ca2+ATPase, β-adrenergic receptors, G-proteins, Na+-K+ATPase, some K +channels
inhibited: β-myosin heavy chain (low ATPase activity), two types of adenyl cyclase, T3 nuclear receptor, Na+-Ca2+exchanger

54
Q

What are catecholamines?

A

norepinephrine and epinephrin
they have similar effects as T3 and T4 but shorter duration (increase metabolic rate, stimulate nervous system, cardio effects

55
Q

Fill in the blank: Injection of T4 __________ toxicity of catecholamines in rat studies.

A

increases

56
Q

True or False. Blocking Beta-adrenergic receptors recudes the action of T3/T4.

A

True

57
Q

Beta-Blockers are used to treat what?

A

Thyroid storms, a thyroid hormone toxicity induced by infection, trauma, drugs. mechanism unclear but can be lethal.

58
Q

How do neurons get their T3?

A

Astrocytes convert T4 to T3 for them.

59
Q

Hypothyroidism can have what effects in relation to the nervous system? What about during development?

A

slow mentation, elevated protein levels in cerebrospinal fluid, placid but can be depressed or agitated
Increased responsiveness to catecholamines
hypothyroidism during development: retardation, motor rigidity, cretinism

60
Q

What effect does hyper and hypothyroidism have on muscles?

A

hyper: muscle weakness due to increased protein catabolism
hypo: muscle weakness, cramps, stiffness

61
Q

What are the effects of the thyroid on carbohydrate metabolism?

A

TH increases carb absorption from the gut

62
Q

What are the effects of the thyroid on cholesterol metabolism?

A

decrease cholesterol levels (more LDL receptors in the liver)

63
Q

What are the effects of the thyroid on the reproductive system?

A

follicular development and ovulation –> women
normal maintenance of pregnancy
spermatogenesis –> man

64
Q

Thyroid hormones play a major role in the growth and development of which tissues?

A

bone (growth, maturation)
teeth (development, eruption)
epidermis, hair follicles, nails (growth, maturation)
skeletal muscle contraction (rate and force)
inhibit synthesis and increases degradation of mucopolysacchararides

65
Q

What are the types of hypothyroidism?

A

Primary - thyroid gland failure (most common)
secondary -pituitary failure (TSH deficiency)
tertiary - hypothalamic failure (TRH deficiency)
Peripheral resistance to action of thyroid hormones

66
Q

What are the signs and symptoms of hypothyroidism? What about in infants?

A

Symptoms: fatigue, coldness, weight gain, constipation, low voice
Signs: cool skin, dry skin, swelling of face/hands/legs, slow reflexes, myxedema
infants: retardation, short stature, swelling, deafness possibly

67
Q

What biochemical markers can be used to diagnose hypothyroidism?

A

low free T4, high TSH –> primary

low free T4, low TSH –> secondary, tertiary

68
Q

What is the treatment for hypothyroidism? What does it prevent?

A

levothyroxine (T4)

treatment prevents bone loss, cardiomyopathy, myxedema

69
Q

What causes the enlargement of the thyroid in goiter? Why does it occur? What is the original cause leading to this?

A

elevated TSH causes enlargement
occurs to increase iodine uptake efficiency
initially caused by iodine deficiency or certain treatments

70
Q

Iodine deficiency in pregnancy can cause…?

A

neurological damage: cretinism, intellectual impairment, deafness, paralysis

71
Q

True or False. Iodine deficiency is no longer a currently significant issue around the world due to the use of iodized salt.

A

False. Still a current issue, 20 million children born a year with mental deficiencies
Iodized salt has shown a drastic improvement in those countries applying them

72
Q

Describe the importance of thyroid hormones on growth.

A

TH help with bone growth and the epiphysial closure. In hypothyroid children, GH secretion is repressed. T3/T4 also increases the effects of GH. If this happens in newborns, there can also be permanent neurological effects.

73
Q

What are possible causes of congenital hypothyroidism (5)?

A 
Maternal iodine deficiency
abnormal development of fetal thyroid
errors in thyroid hormone synthesis
maternal antithyroid antibodies that cross the placenta
fetal hypopituitary hypothyroidism
74
Q

Describe the concentration of T4 through life stages.

A

T4 is highest in young children, decreases to adult level at puberty then remains stable until 60y. Then it decreases gradually until about 50%. Elderly may develop hypothyroidism which would make them suceptable to cold (winter)

75
Q

When iodine is sufficient, what is the most common cause of hypothyroidism?

A 
autoimmune disease (hashimoto's disease)
usually the immune response is against TPO
76
Q

What lab values can be expected in a person with Hashimoto’s disease? How can it be treated?

A 
High TSH
low T4
anti-TPO Ab
Anti-TG Ab
treated with levothyroxine
77
Q

What is a common cause of hyperthyroidism? What are the symptoms?

A

Grave’s disease (anti-TSH receptor antibodies)

palpiation, nervousness, fatigue, diarrhea, sweating, heat intolerance

78
Q

Describe the consequences of the production of anti-TSH receptor antibodies (grave’s disease)

A

binding to the receptor for TSH leads to production of T4. TSH is inhibited by excess T4, but the receptor is still being triggered

79
Q

What lab values can be expected in someone with Grave’s disease?

A

low TSH
normal/high FT4
anti-TSH receptor Ab

80
Q

True or False. Since clinical signs of Grave’s disease are exophtalmus and goiter , is is easily and quickly diagnosed.

A

False. Symptoms develop gradually and it takes an average of 3 years before diagnosis

81
Q

What treatments are used for Grave’s disease?

A

anti-T4 compounds (Propothyouracil, Methimazole, Propranolol)
surgery (subtotal thyroidectomy)
Radiation

82
Q

Other than Grave’s disease, what other possible cause is there for hyperthyroidism?

A

T4 secreting tumors or RARELY TSH secreting tumors

Metabolic endocrinology 2 (4 decks)

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