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Endocrinology and Reproduction > Thyroid Physiology II > Flashcards

Thyroid Physiology II Flashcards

1
Q

Are extremely hydrophobic and hence, readily enter target cells by passive diffusion across outer and nuclear membranes

A

T3 and T4

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2
Q

Once in the nucleus, T3 and T4 specifically bind to their

A

Cognate receptors

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3
Q

The receptors for thyroid hormone (thyroid hormone receptors or TRs) are members of the nuclear hormone receptor superfamily that serve as

A

Ligand-activated transcription regulatory proteins

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4
Q

There are two very similar human TR subtypes, α and β, encoded on two different genes found on chromosomes

A

17 and 3 respectively

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5
Q

Both TRa and TRB bind to DNA as a heterodimer with another nuclear hormone called

A

RXR

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6
Q

Specific DNA sequesnces that serve as binding sites for RXR/TR and are found in the promoter region of target genes

A

Thyroid Hormone Response Elements (TREs)

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7
Q

In the absence of hormone, RXR/TR can still bind to DNA, but the unliganded receptors usually facilitate transcriptional repression (i.e., gene silencing) via the recruitment of

A

Corepressor proteins

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8
Q

TR undergoes a conformational change that allows it to recruit coactivator proteins and enzymes in the presence of

A

T3

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9
Q

This typically results in strong transcriptional activation of the

A

Target gene

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10
Q

Which binds TR with a greater affinity of approximately 100x, T3 or T4?

A

T3

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11
Q

Because thyroid hormone acts at the level of gene expression, man of its effects can be blocked by inhibitors of

A

Protein synthesis (such as cycloheximide)

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12
Q

This also accounts for the 12- to 48-hour delay (or latent

period) before most of thyroid hormones’ physiological effects become

A

Evident in vivo

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13
Q

The best documented physiological effect of thyroid hormone is to increase almost every tissue types (except the brain, spleen, and testes)?

A

Basal Metabolic Rate (BMR)

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14
Q

The hormone induced increase in BMR is associated with a significant increase in

A

Oxygen consumption and production of heat

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15
Q

Stimulates the BMR in part by increasing the
number and size of mitochondria as well as directly upregulating the expression of mitochondrial respiratory enzymes required for increased ATP production

A

Thyroid Hormone

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16
Q

To compensate for the increased demand for oxygen (the result of an elevated BMR), thyroid hormones act directly and indirectly on cardiac muscle, having what effect?

A

Increase contractility and cardiac output

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17
Q

The direct effects of thyroid hormone on cardiac muscle are evident as an upregulation in

A

Actin, myosin, and Ca2+ and myosin stimulated ATPases

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18
Q

Indirect effects include enhancing the speed and force of myocardial contractions by potentiating stimulation by the

A

SNS

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19
Q

Indirectly upregulates the expression of beta adrenergic receptors in cardiac muscle cells

A

Thyroif hormone

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20
Q

Physiologically, increased oxygen consumption (the result of an elevated BMR) must be accompanied by increased

A

Energy consumption

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21
Q

Thyroid hormone increases cellular energy expenditure by activating the expression of the

A

Na+/K+ ATPase

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22
Q

As much as 20-80% of the basal energy used by a resting cell is devoted towards maintaining the gradient produced by the

A

Na+/K+ ATPase

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23
Q

The Na+/K+ ATPase generates large amounts of

A

ADP and heat

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24
Q

Also increase energy expenditure by stimulating futile cycling of protein, carbohydrate and fat metabolism (i.e., simultaneously stimulating both anabolic and catabolic pathways)

A

Thyroid Hormones

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25
Q

In general, leads to an overall increase in protein,

lipid and glycogen turnover with the catabolic pathways ultimately predominating

A

Hyperthyroidism

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26
Q

Thus, hyperthyroid patients tend to

A

Lose weight

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27
Q

Leads to an overall decrease in metabolic turnover

A

Hypothyroidism

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28
Q

Thyroid hormones are important in maintaining a constant body temperature. This is called

A

Thermoregulation

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29
Q

Have an elevated body temperature and a lower tolerance to heat

A

Hyperthyroid patients

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30
Q

Experience a decreased tolerance to cold

A

Hypothyroid patients

31
Q

T3/T4’s ability to increase oxygen consumption and generate body heat can also be accounted for through a process termed

A

Facultative thermogenesis

32
Q

In brown adipose tissue (BAT), T3/T4 acts in concert with stimulation from the sympathetic nervous system (SNS) to upregulate the expression of

A

Uncoupling protein-1 (UCP-1)

33
Q

Acts in the mitochondria to create a ‘leakage’ of protons across the inner mitochondrial membrane essentially short-circuiting the respiratory chain

A

UCP-1

34
Q

Thus, although oxygen continues to be utilized at a high rate, very little ATP is synthesized. Rather, most of the available energy is simply lost as

A

Heat

35
Q

Crucial for normal linear growth of adolescents into

adults and attainment of a normal adult stature depends on optimal levels

A

Thyroid hormone

36
Q

Early in infancy, thyroid hormone is required for the synthesis of

A

hGH (aka somatotropin)

37
Q

Biochemical studies suggest thyroid hormone can directly stimulate osteoblasts to produce

A

IGF-1, alkaline phosphatase, and osteocalcin

38
Q

Thyroid hormone is thought to function synergistically with hGH and other insulin-like growth factors (somatomedins) to promote

A

Linear bone growth

39
Q

Uncorrected hypothyroidism during childhood results in linear growth retardation and malformation of facial bones. This condition is termed as

A

Juvenile hypothyroidism or cretinism

40
Q

In adults, excess T4/T3 (hyperthyroidism) promotes

A

Osteoporosis

41
Q

Are essential for the normal development and maturation of the CNS during fetal development and early infancy

A

Thyroid hormones

42
Q

The most important period for thyroid hormone action on the CNC

-the period just before and just after birth during which there is an absolute requirement for thyroid hormone signaling

A

Perinatal period

43
Q

Promotes the development and maturation of the CNS by regulating myelinogenesis and synapse formation as well as neuronal outgrowth, proliferation, and differentiation

A

T4/T3

44
Q

During the critical perinatal period, thyroid hormone must be present for the normal development of the

A

Brain

45
Q

Results in severe, irreversible mental retardation, even if large doses of T4/T3 are given later in life

A

Neonatal hypothyroidism

46
Q

Neonatal hypothyroidism can be averted by

A

Immediate post natal administration of T4/T3

47
Q

Produces hyperexciteability, irritability, and restlessness in adults

A

Hyperthyroidism

48
Q

Display listlessness, lack of energy, slowness of speech, decreased sensory capacity and impaired memory

A

Hypothyroid adults

49
Q

The most common cause of hyperthyroidism is an autoimmune stimulation of thyroid follicular cell TSH receptors called

A

Grave’s disease

50
Q

Results in hyperplasia of the entire thyroid gland and unsuppressed production of T3/T4

A

Grave’s Disease

51
Q

The second most common cause of hyperthyroidism is

A

Benign neoplasms in thyroid

52
Q

The least common causes are excessive pituitary secretion of TSH, ingestion of exogenous T3/T4, and hyper-activating mutations of TR genes

A

Hyperthyroidism

53
Q

In most cases of hyperthyroidism, there is an excessive thyroid uptake of

A

Iodine

54
Q

Serum TSH levels are concomitantly low because the hypothalamus and pituitary glands are suppressed by the high levels of

A

T3/T4

55
Q

Are there cases of hyperthyroidism where both T3/T4 levels and TSH levels are high?

A

Yes

56
Q

The symptoms of hyperthyroidism in adults are striking and are primarily due to an elevated

A

Metabolic rate

57
Q

Excitability and nervousness are due to the action of T3/T4 on the

A

CNS

58
Q

Can cause eye ball protrusion (exopthalmos) due to edematous swelling of the retro orbital tissues and degenerative changes in the extraoccular muscles

A

Hyperthyroidism

59
Q

Exopthalmos is not due to elevated T3/T4 levels, but rather the result of

A

Anit-TSH receptor autoimmunity

60
Q

What are three possible treatments of hyperthyroidism?

A
  1. ) Propylthiouracil
  2. ) radioactive thyroid ablasion
  3. ) Surgical removal of thyroid
61
Q

Inhibits the enzymatic action of TPO

A

Propylthiouracil

62
Q

The most common cause of hypothyroidism is an autoimmune destruction of the thyroid gland (thyroiditis) in which antibodies either block T3/T4 synthesis or cause atrophy of the gland. An example of this is

A

Hashimoto’s Thyroditis

63
Q

Hypothalamus or pituitary disorders that inhibit TSH

secretion, or iodine deficiency in the diet can both cause

A

Hypothyroidism

64
Q

Iodine deficiency in the diet is known as

A

Endemic cretinism

65
Q

In rare cases, mutant TR’s can cause

A

Hypothyroidism

66
Q

Hypothyroidism due to a mutation in a TR is called

A

Generalized resistance to thyroid hormone

67
Q

IF the hypothyroidism is caused by hypothalamic or pituitary failure than TSH will be

A

Decreased

68
Q

Otherwise, Hypothyroidism means that TSH is

A

Elevated

69
Q

Weight gain, decreased heart rate and cardiac output, and decreased heat production (and thus cold intolerance) are common with

A

Hypothyroidism

70
Q

Movement, speech and thought are all slowed and lethargy, sleepiness, and a lowering of the upper
eyelids (ptosis) occur with

A

Hypothyroidism

71
Q

An accumulation of mucopolysaccharides in various tissues can occur which in turn results in a diffuse accumulation of extracellular fluid termed

A

Myxedema

72
Q

When the primary disorder of hypothyroidism is at the level of the thyroid gland itself, goiter can occur due to the relentless stimulation of the thyroid gland by high circulating levels of

A

TSH

73
Q

Treatment for hypothyroidism involves

-in most cases is entirely curative

A

T4 hormone replacement therapy

74
Q

Is generally not used to treat hypothyroidism given its short ½-life in the blood stream

A

T3

Endocrinology and Reproduction (15 decks)

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