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Endocrinology and Reproduction > Thyroid Physiology I > Flashcards

Thyroid Physiology I Flashcards

1
Q

A bilobed gland attached to the lower ventral surface of the trachea and connected by a band of tissue called the isthmus

A

The Thyroid

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2
Q

Both lobes receive arterial blood via thyroid arteries and are innervated by the sympathetic nervous system that controls

A

Blood flow

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3
Q

The thyroid gland contains follicles of epithelial cells that are the site of

A

Thyroid hormone synthesis

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4
Q

Thyroid hormone is stored in the follicle lumen as a clear viscous substance termed

A

Colloid

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5
Q

Interspersed among the follicles are parafollicular cells (C ells) which secrete

A

Calcitonin

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6
Q

A peptide hormone involved in calcium metabolism

A

Calcitonin

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7
Q

Stimulates the thyroid to secrete thyroid hormone into the blood stream

A

Thyroid Stimulating Hormone (TSH)

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8
Q

The most important function of thyroid hormone in adults is to regulate the overall rate of

A

Body metabolism

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9
Q

Are among the most common endocrine disorders in the U.S. affecting an estimated 10% of the population

A

Hyper and Hypothyroidism

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10
Q

Thyroid hormones are a series of compounds produced by the coupling of iodonated tyrosine molecules called

A

Iodinated thyronines

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11
Q

About 91% of the thyroid hormone produced and secreted by the thyroid gland is in the form of

A

Thyroxine (T4)

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12
Q

Has relatively weak biological activity

A

T4

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13
Q

The most biologically active of the thyroid hormones and constitutes only 7% of the hormone load secreted by the thyroid

A

Triiodothyronine (T3)

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14
Q

Comprises 2% of the hormone secreted by the thyroid and has no known biological activity

A

Reverse T3 (rT3)

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15
Q

Thyroid hormone is synthesized by

A

Thyroid epithelial cells (follicular cells)

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16
Q

Display a pronounced functional polarity from their basal to apical membranes

A

Follicular cells

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17
Q

Trap inorganic iodide (I-) through an ATP-requiring process involving a basal membrane I- pump (Na/I symporter)

A

Follicular cells

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18
Q

The efficiency and specificity of follicular iodide trapping results in 90% of the total body iodine being concentrated in the

A

Thyroid

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19
Q

Once transported into the follicular cell, iodide is incorporated into thyroid hormone precursors through which three processes?

A
  1. ) Oxidation
  2. ) Iodination
  3. ) Coupling
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20
Q

Inorganic iodide is oxidized into an active intermediate by

A

Thyroid Peroxidase (TPO)

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21
Q

A membrne bound enzyme located on the apical cell surface of the thyroid

A

TPO

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22
Q

What does TPO require as an oxidizing agent?

A

Hydrogen Peroxide

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23
Q

Iodination (or organification) of tyrosine residues is also catalyzed by

A

TPO

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24
Q

Rather than iodinate free tyrosine amino acids, ‘active iodine’ is added to the approximately 120 140 tyrosine residues found within a 660 kD, thyroid specific glycoprotein termed

A

Thyroglobulin (TG)

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25
Q

Synthesized on the rough endoplasmic reticulum of
thyroid follicular cells, packaged into endocytotic vesicles, and then extruded into the follicle lumen where it becomes a substrate for TPO

A

Thyroglobulin (TG)

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26
Q

Iodination results in the incorporation of either one or two iodines per TG-tyrosine residue resulting in

A

Monoiodotyrosine (MIT) or diiodotyrosine (DIT) respectively

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27
Q

Further catalyzes the coupling of either two DITs to form tetraiodothyronine (T4), or one MIT plus one DIT to form triiodothyronine (either T3 or rT3)

A

TPO

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28
Q

The iodonated TG protein (containing thyroid hormone molecules) is stored in the lumen of the follicle. This form of TG is termed

A

Colloid

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29
Q

Pathology where the development of autoimmune antibodies against TPO and/or TG disrupts normal thyroid hormone synthesis and leads to hypothyroidism

A

Hashimoto’s thyroiditis

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30
Q

Hashimoto’s thyroiditis leads to

A

Hypothyroidism

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31
Q

For thyroid hormone secretion to occur, colloid must be brought back into the follicular cell by

A

Endocytosis

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32
Q

Pseudopodia on the lumenal membrane surface engulf colloid droplets and transport them back into the cell upon stimulation by

A

TSH

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33
Q

Once within the cell, the colloid droplets fuse with lysosomes which degrade the colloid and release the

A

Iodinated tyrosines and thyronines into the cytoplasm

34
Q

MITs and DITs are rapidly deiodinated by cytoplasmic enzymes producing free iodine and tyrosine residues, which are recycled into new

A

Thyroglobulin/colloid synthesis

35
Q

Although the more biologically potent T3 comprises only 7% of the thyroid gland output (~6 µg per day), the total daily production of T3 is increased almost 6-fold (35 µg) by the conversion of

A

T4 into T3 in peripheral tissues

36
Q

The conversion of T4 to T3 (i.e. the removal of an iodine from the 5’-position of outer phenyl ring) is catalyzed by the enzyme

A

5’-deiodinase

37
Q

5’-deiodinase is found predominantly in the

A

Liver and Kidneys

38
Q

Hence, the majority of circulating T3 (biologically active) is derived from

A

T4

39
Q

T4 can also be converted into the biologically inactive rT3 by 5-deiodinase, an enzyme that removes an iodine from the

A

5-position of inner phenyl ring

40
Q

Upon secretion into blood, thyroid hormones are predominantly bound to

A

Plasma proteins

41
Q

Thus serve as a reservoir of thyroid hormone, preventing renal clearance and providing free hormone as needed

A

Plasma binding proteins

42
Q

About 80% of the T4 circulating in blood is bound to

A

Thyroxine-binding globulin (TBG)

43
Q

The remaining 20% is bound to

A

Transthyretin and albumin

44
Q

The affinity of T4 for the binding proteins is so great that only 0.04% of the total T4 in circulation is

A

Unbound

45
Q

Most of the circulating T3 is bound to

A

TBG

46
Q

Only trace amounts of T3 is bound to

A

Transthyretin and albumin

47
Q

T3 has a slightly lower affinity for the binding proteins. Thus what percentage of T3 remains unbound?

A

0.4%

48
Q

What has a longer half-life, T3 or T4?

A

T4 (because it is more tightly bound to proteins

49
Q

In view of T4’s long half-life and its ability to be converted into the more biologically potent T3, T4 is considered to be a

A

Pro-hormone (i.e. circulating precursor) for T3

50
Q

The major activator of thyroid hormone production is

A

TSH (aka thyrotropin)

51
Q

A heterodimeric glycoprotein (composed of an α and β subunit) synthesized and secreted by thyrotrophic cells of the anterior pituitary

A

TSH (thyrotropin)

52
Q

TSH production and secretion from pituitary thyrotrophs is in turn, stimulated by the neurohormone

A

Thyrotropin-Releasing Hormone (TRH)

53
Q

A three amino acid peptide produced in the hypothalamus

A

TRH

54
Q

In response to environmental stimulus, TRH is secreted by the hypothalamus and reaches the anterior pituitary via the

A

Hypophyseal portal sytem

55
Q

What stimulates the TRH secretion by the hypothalamus?

A

Cold temp, increased caloric intake, leptin

56
Q

TRH-stimulated thyrotrophs secrete TSH into the blood-stream, which ultimately bind specific high affinity TSH receptors on the surface of

A

Thyroid follicular cells

57
Q

Members of the G protein-coupled receptor family and stimulate membrane-bound adenylate cyclase when activated by TSH

A

TSH receptors

58
Q

The resulting increase in intracellular cAMP concentration subsequently activates the entire

A

Thyroid hormone biosynthesis pathway

59
Q

TSH stimulation of thyroid follicular cells induces activation of

A

TG and TPO expression

60
Q

TSH stimulation of thyroid follicular cells induces

A

Activation of Na+/K+ ATPase expression

61
Q

TSH stimulation of thyroid follicular cells induces enhancement of the enzymatic rate of

A

Oxidation, iodination, and coupling

62
Q

TSH stimulation of thyroid follicular cells induces stimulation of the uptake of

A

Colloid droplets

63
Q

TSH stimulation of thyroid follicular cells induces the uptake and oxidation of glucose, providing substrate for the

A

Pentose monophosphate shunt (Leads to NADPH and H2O2 production)

64
Q

TSH stimulation of thyroid follicular cells induces stimulation of the fusion of colloid droplets with lysosomes, which ultimately leads to the release of

A

T3 and T4

65
Q

Additionally, TSH exerts a ‘tonic maintenance’ effect on the thyroid gland by increasing the size and number of follicular cells and increasing the

A

Vascularity of the gland

66
Q

Pathological hyperstimulation of the thyroid gland by TSH can lead to an abnormal enlargement or swelling of the gland termed

A

Goiter

67
Q

Elevated serum levels of T3 and T4 (the result of TSH stimulation) produce a negative feedback both at the

A

Hypothalamus and pituitary gland

68
Q

This in turn inhibits the

A

TRH- and TSH-signaling pathways

69
Q

In both cases, elevated T3/T4 is thought to inhibit TRH and TSH production at the level of

A

Gene expression

70
Q

Quantitation of both TSH and T4/T3 serum concentrations provides the basis for accurate diagnosis of

A

Thyroid disorders

71
Q

When the primary disorder stems from the thyroid gland itself, there is typically an inverse correlation between

A

T3/T4 levels and TSH levles

72
Q

Elevated T4/T3 concentrations with suppressed TSH levels reveals

A

Hyperthyroidism

73
Q

Abnormally low T4/T3 concentrations together with high TSH levels reveals

A

Hypothyroidism

74
Q

A HYPERthyroid condition where autoantibodies recognize and pathologically activate thyroid TSH receptors

A

Grave’s disease

75
Q

The result of Grave’s disease is

A

Abnormally high T3/T4 and low to immeasurable TSH

76
Q

As discussed above, the circulating concentration of biologically active T3 is determined not only by its production and secretion from the thyroid gland, but also by the activity of

A

5’ deiodinase

77
Q

Can result in decreased serum T3 levels and increased (inactive) rT3 levels

A

Increased 5’-deiodinase activity

78
Q

For instance, during fasting or a severe debilitating illness, serum T3 levels will decrease while

A

rT3 levels rise

79
Q

In such cases, TSH levels paradoxically remain in a
normal to low range, presumably due to decreased TRH secretion and the inhibiting action of other hormones and factors at the

A

Pituitary gland

80
Q

What is the purpose of decreasing T3 levels in this way (called euthyroid sick syndrome)?

A

To conserve energy and body tissue during a depleted state

Endocrinology and Reproduction (15 decks)

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