McCumbee - Thyroid Hormones

Question 1

Enlarged thyroid gland

Answer 1

Goiter

Question 2

The functional unit of the thyroid gland is the ?

Answer 2

Follicle

Question 3

The principle component of the thyroid follicle is within the colloid, it a glycoprotein called _____

Answer 3

Thyroglobulin

Question 4

Principle thyroid hormone secreted by thyroid follicles _

Answer 4

Thyroxine (T4)

Question 5

Parafollicular (C cells) are in the stroma of the thyroid, surround the follicles. These cells secrete ______

Answer 5

Calcitonin

Question 6

The thyroid gland removes Iodide from circulation by ?

Answer 6

Iodine trapping

Uses a Na-Iodide symporter

Question 7

In a normal euthyroid individual. The NIS pump maintains a T/S ratio of idodide (ratio of concentration in follicle cell to that in serum) that is_____

Answer 7

About 30

Question 8

Anions that can competitively interfere with the NIS transporter are ? (X3)

Answer 8

Perchlorate (HClO4-)
Thiocyanate(CNS-)
Pertechnetate (TcO4-)

Question 9

As the iodide molecules into the follicular lumen of in the thyroid _________ catalyzes their oxidation.

Answer 9

Thyroid peroxidase (TPO)

Question 10

What does thyroid oxidase do ?

Answer 10

In the creation of thyroid hormones, when iodide is oxidated by thyroid peroxidase when crossing the apical membrane of the follicular cell, Thyroid oxidase facilitates H2O2 accepting the extra electron.

Question 11

T3 and T4 are stored where?

Answer 11

Outside the cell within the colloid of the follicular lumen

Question 12

Thyroglobulin is an important reservoir of iodide in the form of ____ and ____

Answer 12

MIT

DIT

Question 13

The coupling reaction of MIT and DIT forms T4 and T3

This reaction is catalyzed by ?

Answer 13

Thyroid peroxidase

Question 14

Coupling DIT and DIT forms

Answer 14

T4

Question 15

Coupling DIT and MIT forms

Answer 15

T3

Question 16

In a normal adult, there is enough thyroid hormone stored as thyroglobulin to maintain euthyroid condition for ___

Answer 16

2 to 3 months

Question 17

Thyroid hormone release into circulation requires _____ of thyroglobulin from the colloid

Answer 17

Proteolysis

The colloid fragments are then endocytosed at apical surface of follicle cell

Question 18

What happens in people that are deficient in the microsomal deiodinase “idotyrosine deiodinase”.

Answer 18

This enzyme is involved in recycling MIT and DIT.

People deficient in it have hypothyroidism and elevated serum and urine DIT and MIT

Question 19

Most circulating T3 and T4 are bound to plasma proteins (T4 .03% free T3 0.3% free)
What are the 3 binding proteins?

Answer 19

Thyroxine-binding globulin

Transthyretin

Albumin

Question 20

TBG levels decreases in response to _____ (x3)

Answer 20

Malnutrition

Liver disease (decreased synthesis)

Kidney disease (increased loss in urine)

Question 21

Hepatic TBG synthesis is stimulated by _______

Answer 21

Estrogens

Question 22

_______ cause decreased thyroid hormone binding to TBG

Answer 22

Salicylates

Question 23

What are the roles of thyroid hormone binding proteins/

Answer 23

Serve as a reserve capacity

Increase amount carried in plasma since these hormones are insoluble

Decrease amount of the small T3 and T4 molecules lost in urine.

Question 24

Circulatory half life of T4 is ____

Circulatory half life of T3 is ___

Answer 24

6-7 days

1 days

Question 25

The majority of the circulating T3 comes from ____

Answer 25

The peripheral metabolism of T4 Mostly converted at the kidney and liver

Question 26

The major source of serum T3 (metabolized from T4) is the _____ and ____-

Answer 26

Liver Kidney

Question 27

What are the important physiological roles of peripheral iodothyronine deiodinases (x3)

Answer 27

Maintain circulatory pool of T3 Regulation of iodothyronine deiodinases at specific tissues allows for independent regulation of T3 levels at different tissues Thyroid hormone inactivation

Question 28

The most important hormone regulating the thyroid gland is _____

Answer 28

TSH

Question 29

Due to actions of _____ and _____, thyroid deficient patients being treated w/ T4 usually have normal levels of T3

Answer 29

D1 and D2 Deiodinaes

Question 30

Thyroid stimulating hormone (TSH) secretion is _______ by thyrotropin releasing hormone

Answer 30

Stimulated

Question 31

TSH (thyroid stimulating hormone) secretion is __—-_- by T4 and T3

Answer 31

Inhibited

Question 32

TSH stimulates:

Answer 32

Iodide trapping Endocytosis and proteolysis of colloid Expression of genes for thyroglobulin, thyroid peroxidase, and NIS Increase in size and number of follicle cells Increase in capillary. Proliferation and blood flow thru the thyroid

Question 33

How does TSH work?

Answer 33

The TSH receptor is coupled to a Gs protein which activates adenylyl cyclase and makes cAMP which induces the various responses to TSH

Question 34

Chronic TSH stimulation will lead to ?

Answer 34

Increased thyroid gland size (bigger follicle cells, more proliferation)) And Increased capillary perfusion

Question 35

Immediate effects of TSH stimulation are:

Answer 35

Increased endocytosis and proteolysis of colloids Uptake of iodide Release of thyroid hormone Activation of thyroid peroxidase

Question 36

In the pituitary, what does TRH do?

Answer 36

It stimulates the synthesis and release of TSH

Question 37

T3 and T4 do what to the pituitary release of TSH?

Answer 37

Inhibit it thru negative feedback mechanism.

Question 38

Thyroid hormone receptors are ligand activated _______

Answer 38

Transcription factors

Question 39

Thyroid hormone receptors are ________ sensitive to T4 than to T3

Answer 39

Less

Question 40

What do Thyroid hormone receptors do once bound by T3?

Answer 40

Bind DNA sequences called thyroid hormone response elements (TRE’s) in regulatory regions of genes. They bind as monomers, homodimers, or heterodimers. Highest affinity is w/ Retinoid X receptor paired TRE’s

Question 41

When is the highest affinity binding of T3?

Answer 41

When heterodimers of THR-Retinoid x receptors are found

Question 42

Where are THR usually at when not bound to T3?

Answer 42

Usually bound to the TRE segment on DNA, working as an inhibitor of transcription

Question 43

At the cellular level, thyroid hormones work primarily by?

Answer 43

Regulating the transcription of genes

Question 44

Thyroid hormone will _________ the transcription of the Na/K ATPase

Answer 44

Activate

Question 45

Thyroid hormone will ________ the beta-adrenergic receptor

Answer 45

Activate

Question 46

TH _______ the sensitivity of various tissues to catecholamine stimulations

Answer 46

Increases (by increasing synthesis of beta-adrenergic receptors) [TH can mimic the effects of the catecholamines]

Question 47

The energy required to maintain bodily functions at a state of complete rest

Answer 47

Basal metabolic rate (BMR) Determined by heat production or indirectly by measuring O2 consumption.

Question 48

TH works directly and indirectly to _______ cardiac output and respiratory rate

Answer 48

Increase

Question 49

How does thyroid hormone increase basal metabolic rate?

Answer 49

By increasing gluconeogenesis, glycogenolysis, lipolysis, and proteolysis. Also indirectly by increasing cardiac output and respiratory rate

Question 50

How does TH effect cardiovascular system?

Answer 50

TH increases transcription of beta adrenergic receptors. This winds up increasing the force and rate of cardiac contraction.

Question 51

What are causes of congenital hypothyroidism?

Answer 51

Infants w/ little-no thyroid tissue (80-85% of cases) Infants who lack proper enzymes for TH synthesis or metabolism Infants whose mothers have autoimmune dz and pass THR-antibodies to baby. Places w/ endemic iodide deficiency

Question 52

What proteins do the antibodies produced in hashimoto thyroiditis interact with?

Answer 52

Thyroid peroxidase (TPO) Thyroid globulin (TG) TSH-receptor

Question 53

Most common cause of hypothyroidism in the US

Answer 53

Hashimoto thyroiditis (95%)

Question 54

Explain hashimoto thyroiditis

Answer 54

Autoimmune dz. Body makes antibodies for TPO, TG, and TSH-R proteins. Follicle cells eventually destroyed, leading to hypothyroidism. Most common cause of hypothyroid in US.

Question 55

What is the cause of secondary hypothyroidism?

Answer 55

Hypofunctional pituitary; Isolated TSH deficiency Second to surgery, trauma, infiltrative disorders

Question 56

Early s/s of hypothyroidism | *(x9)

Answer 56

``` Tiredness Weight gain Brittle hair/ nails Reduced muscle tone Increased muscle cramps Joint pain Carpal tunnel syndrome. Insensitivity to cold (increased) Constipation ```

Question 57

Generalized non-pitting edema caused by the accumulation of mucopolysaccharides in CT. Produces thickened skin and facial features, enlarged tongue, periorbital edema, hoarseness, and joint stiffness

Answer 57

Myxedema

Question 58

Later symptoms of hypothyroidism | X3

Answer 58

Slowed speech Myxedema Women may have irregular periods

Question 59

What are the symptoms of thyrotoxicosis

Answer 59

Increased metabolic activity in T3 sensitive tissue Increased catecholamine sensitivity

Question 60

What is Graves disease?

Answer 60

Graves disease is the number 1 cause of thyrotoxicosis. It has a characteristic hyperplastic goiter as well as thyrotoxicosis s/s. 80% of patients have thyroid-related opthalmopathy . Patients have a Thyroid-stimulating immunoglobulin (TSI) which has the same effects TSH on the TSH-R.

Question 61

What are the characteristics of thyroid - associated opthalmopathy?

Answer 61

Periorbital edema and proptosis

Question 62

Bulging of the eyeyballs

Answer 62

Proptosis

Question 63

Causes of thyrotoxicosis?

Answer 63

Graves disease (thyroid stimulating immunoglobulin) Toxic adenoma Toxic multinodular goiter TSH secreting pituitary adenoma

Question 64

Explain toxic Adenomas

Answer 64

You get a solitary, hyperfunctioning adenoma in the thyroid, most patients have gain in function mutations of the TSH receptor