Thyroid Physiology I

Question 1

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

Answer 1

The Thyroid

Question 2

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

Answer 2

Blood flow

Question 3

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

Answer 3

Thyroid hormone synthesis

Question 4

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

Answer 4

Colloid

Question 5

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

Answer 5

Calcitonin

Question 6

A peptide hormone involved in calcium metabolism

Answer 6

Calcitonin

Question 7

Stimulates the thyroid to secrete thyroid hormone into the blood stream

Answer 7

Thyroid Stimulating Hormone (TSH)

Question 8

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

Answer 8

Body metabolism

Question 9

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

Answer 9

Hyper and Hypothyroidism

Question 10

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

Answer 10

Iodinated thyronines

Question 11

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

Answer 11

Thyroxine (T4)

Question 12

Has relatively weak biological activity

Answer 12

T4

Question 13

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

Answer 13

Triiodothyronine (T3)

Question 14

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

Answer 14

Reverse T3 (rT3)

Question 15

Thyroid hormone is synthesized by

Answer 15

Thyroid epithelial cells (follicular cells)

Question 16

Display a pronounced functional polarity from their basal to apical membranes

Answer 16

Follicular cells

Question 17

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

Answer 17

Follicular cells

Question 18

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

Answer 18

Thyroid

Question 19

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

Answer 19

1. ) Oxidation
2. ) Iodination
3. ) Coupling

Question 20

Inorganic iodide is oxidized into an active intermediate by

Answer 20

Thyroid Peroxidase (TPO)

Question 21

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

Answer 21

TPO

Question 22

What does TPO require as an oxidizing agent?

Answer 22

Hydrogen Peroxide

Question 23

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

Answer 23

TPO

Question 24

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

Answer 24

Thyroglobulin (TG)

Question 25

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

Answer 25

Thyroglobulin (TG)

Question 26

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

Answer 26

Monoiodotyrosine (MIT) or diiodotyrosine (DIT) respectively

Question 27

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)

Answer 27

TPO

Question 28

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

Answer 28

Colloid

Question 29

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

Answer 29

Hashimoto's thyroiditis

Question 30

Hashimoto's thyroiditis leads to

Answer 30

Hypothyroidism

Question 31

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

Answer 31

Endocytosis

Question 32

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

Answer 32

TSH

Question 33

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

Answer 33

Iodinated tyrosines and thyronines into the cytoplasm

Question 34

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

Answer 34

Thyroglobulin/colloid synthesis

Question 35

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

Answer 35

T4 into T3 in peripheral tissues

Question 36

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

Answer 36

5'-deiodinase

Question 37

5'-deiodinase is found predominantly in the

Answer 37

Liver and Kidneys

Question 38

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

Answer 38

T4

Question 39

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

Answer 39

5-position of inner phenyl ring

Question 40

Upon secretion into blood, thyroid hormones are predominantly bound to

Answer 40

Plasma proteins

Question 41

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

Answer 41

Plasma binding proteins

Question 42

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

Answer 42

Thyroxine-binding globulin (TBG)

Question 43

The remaining 20% is bound to

Answer 43

Transthyretin and albumin

Question 44

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

Answer 44

Unbound

Question 45

Most of the circulating T3 is bound to

Answer 45

TBG

Question 46

Only trace amounts of T3 is bound to

Answer 46

Transthyretin and albumin

Question 47

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

Answer 47

0.4%

Question 48

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

Answer 48

T4 (because it is more tightly bound to proteins

Question 49

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

Answer 49

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

Question 50

The major activator of thyroid hormone production is

Answer 50

TSH (aka thyrotropin)

Question 51

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

Answer 51

TSH (thyrotropin)

Question 52

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

Answer 52

Thyrotropin-Releasing Hormone (TRH)

Question 53

A three amino acid peptide produced in the hypothalamus

Answer 53

TRH

Question 54

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

Answer 54

Hypophyseal portal sytem

Question 55

What stimulates the TRH secretion by the hypothalamus?

Answer 55

Cold temp, increased caloric intake, leptin

Question 56

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

Answer 56

Thyroid follicular cells

Question 57

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

Answer 57

TSH receptors

Question 58

The resulting increase in intracellular cAMP concentration subsequently activates the entire

Answer 58

Thyroid hormone biosynthesis pathway

Question 59

TSH stimulation of thyroid follicular cells induces activation of

Answer 59

TG and TPO expression

Question 60

TSH stimulation of thyroid follicular cells induces

Answer 60

Activation of Na+/K+ ATPase expression

Question 61

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

Answer 61

Oxidation, iodination, and coupling

Question 62

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

Answer 62

Colloid droplets

Question 63

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

Answer 63

Pentose monophosphate shunt (Leads to NADPH and H2O2 production)

Question 64

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

Answer 64

T3 and T4

Question 65

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

Answer 65

Vascularity of the gland

Question 66

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

Answer 66

Goiter

Question 67

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

Answer 67

Hypothalamus and pituitary gland

Question 68

This in turn inhibits the

Answer 68

TRH- and TSH-signaling pathways

Question 69

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

Answer 69

Gene expression

Question 70

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

Answer 70

Thyroid disorders

Question 71

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

Answer 71

T3/T4 levels and TSH levles

Question 72

Elevated T4/T3 concentrations with suppressed TSH levels reveals

Answer 72

Hyperthyroidism

Question 73

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

Answer 73

Hypothyroidism

Question 74

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

Answer 74

Grave's disease

Question 75

The result of Grave's disease is

Answer 75

Abnormally high T3/T4 and low to immeasurable TSH

Question 76

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

Answer 76

5' deiodinase

Question 77

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

Answer 77

Increased 5'-deiodinase activity

Question 78

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

Answer 78

rT3 levels rise

Question 79

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

Answer 79

Pituitary gland

Question 80

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

Answer 80

To conserve energy and body tissue during a depleted state