PHYS - Thyroid Gland

Question 1

What is T4?

Answer 1

Tetraiodothyronine is a prohormone synthesized by the thyroid gland

Question 2

What is T3?

Answer 2

Triiodothyronine is an active hormone synthesized by the thyroid gland

Question 3

What are parafollicular C cells?

Answer 3

Cells outside the follicles of the thyroid gland that secrete Calcitonin

Question 4

Which cells synthesize the thyroid hormones?

Answer 4

Follicular epithelial cells that surround the follicles containing colloid

Question 5

What is colloid composed of?

Answer 5

Colloid is composed of newly synthesized thyroid hormones attached to thyroglobulin

Question 6

What is the ratio of synthesized thyroid hormone (T4:T3)

Answer 6

T4:T3

10:1

Question 7

What is the enzyme responsible for converting T4 into T3?

Answer 7

Deiodinase enzyme

Question 8

What is the inactive form of T3?

Answer 8

Reverse T3 is inactive

It has an iodine missing from the wrong benzene ring

1% of synthesized thyroid hormone is made into Reverse T3

Question 9

What are the sources of T3?

Answer 9

80-90% of T3 is produced via peripheral conversion (via deiodoinase)

10-20% of T3 is directly secreted from the thyroid gland

Question 10

What can cause a decrease in conversion of T4 to T3?

Answer 10

Fasting
Medical and Surgical stress
Catabolic disease

Question 11

What is the NIS channel?

Answer 11

It is a Na+/I- symporter on the apical membrane of the follicular cells of the thyroid gland

It transports 2 Na+ for every I-

It is also called the Iodine trap

Question 12

What are Pendrin channels?

Answer 12

They are channels found on the basolateral membrane of the follicular cells of the thyroid gland

They are responsible for secreting I- anions into the thyroid follicles

Question 13

What is the role of Thyroid peroxidase?

Answer 13

Thyroid Peroxidase is an enzyme that takes two Iodide (I-) anions and forms molecular Iodine (I2)

Molecular I2 can be added MIT/DIT/Thyroglobulin in the follicle to form the colloid

Question 14

What specifically does TSH do to follicular cells?

Answer 14

TSH stimulates pinocytosis of colloid fluid into the follicular cell which then gets acted on by proteases (lysosomes) to remove the T3 and T4 from the thyroglobulin molecule

T3 and T4 are then secreted into the blood

Question 15

What is thyroglobulin?

Answer 15

Thyroglobulin is a binding protein that is synthesized in the follicular cells of the thyroid gland.

It is translated in the rough ER and packaged in the Golgi before being secreted into the follicle

Thyroglobulin binds to MIT, DIT, T3, and T4 in the follicle. The collection of thyroid hormone and its precursors bound to thyroglobulin is what makes up the colloid fluid

Question 16

Describe the process of thyroid hormone synthesis and secretion

Answer 16

NIS Channel (iodine trap) on the basolateral membrane (facing the blood) brings in one I- anion with two Na+ cations into the follicular cell

Thyroglobulin binding protein is synthesized in the follicular cell and secreted into the follicle

Pendrin channel on the apical membrane (facing the follicle) is an I- anion channel that sends I- into the follicle

Peroxidase enzyme takes two I- anions to form molecular Iodine (I2)

Molecular I2 binds with MIT (to form DIT), DIT (to form T3), and T3 (to form T4)

MIT, DIT, T3, and T4 bind with thyroglobulin binding molecules in the follicle forming the colloid

TSH signaling induces Follicular cells to conduct pinocytosis of the colloid fluid.

Thyroglobulin molecules collected in the follicular cells from pinocytosis interact with proteases to break down the binding proteins, freeing up the thyroid hormone molecules for secretion.

MIT and DIT do not get secreted; instead they interact with deiodinase enzymes, which remove the iodoine molcules from MIT and DIT in order to be recycled back into the follicle

Question 17

What is PTU?

Answer 17

Propylthiouracil

It is a drug that is used to treat hyperthyroidism

PTU blocks the actions of thyroid peroxidase, therefore inhibiting the oxidation of iodide (I-) anions into molecular Iodine

Question 18

What is the function of Perchlorate and Thiocynate?

Answer 18

Perchlorate and Thiocynate are drugs that block the NIS channel on the basolateral membrane of the follicular cells of the thyroid gland, preventing Iodine uptake from the blood into the cell

Question 19

What happens to thyroid hormone synthesis when iodide availability is restricted?

Answer 19

T3 is favored over T4

Question 20

How is thyroid gland activity assessed?

Answer 20

Radioactive iodine uptake test

Question 21

In what state does thyroid hormone travel in the blood?

Answer 21

99% bound to plasma proteins

1% free

Question 22

How do the half lives of T3 and T4 compare?

Answer 22

T4 has a greater half life than T3

T4 = 6 days
T3 = 1 day

Question 23

What are the main binding proteins that carry thyroid hormone in the blood?

Answer 23

TBG (Thyroxine-binding Globulin) - 70%

• Synthesized in the liver
• Has a higher affinity for T4 than T3

Transthyretin (TTR) - 10-15%

Albumin - 15-20%

Question 24

What happens to T4 when it is delivered to the tissues?

Answer 24

T4 is a prohormone

T4 is converted to the active form of thyroid hormone, T3, in the tissues

OR sometimes it is converted to reverse T3 (inactive)

Question 25

How does a T3 resin uptake test work?

Answer 25

A known amount of labelled, free T3 is added to blood. T3 will bind to TBG as long as there are unboundsites available Once all sites are filled, anti-T3 antibodies are added and precipitate out of solution. This allows you to determine the amount of TBG in the blood

Question 26

What happens to TBG levels in hepatic failure and what effect does this have on thyroid hormone function?

Answer 26

Hepatic failure decreases blood levels of TBG (which is synthesized in the liver This causes an increase in levels of free T3 and T4 Increased levels of free T3,T4 provide negative feedback, inhibiting thyroid hormone synthesis

Question 27

What happens to TBG levels during pregnancy, and what effect does this have on thyroid hormone funtion?

Answer 27

TBG levels increase during pregnancy This causes a decrease in levels of free T3,T4 Decreased levels of free T3,T4 promote thyroid hormone synthesis and secretion Total levels of T3, T4 increase, but levels of free T3,T4 remain normal

Question 28

What type of receptor does TSH interact with?

Answer 28

GPCR - specifically Gs Activates Adenylyl cyclase, which causes an increase in cAMP, which activates PKA, which phosphorylates target proteins

Question 29

What is the Wolff-Chaikoff effect?

Answer 29

An inhibitory effect on thyroid hormone synthesis due to excessive Iodine intake

Question 30

What action of thyroid hormone is primarily responsible for the increase in basal metabolic rate?

Answer 30

Thyroid hormones cause an increase in synthesis of Na-K-ATPase channels, which are primarily responsible for the increase in BMR seen with Thyroid Hormone

Question 31

What affect does thyroid hormone have on cardiac tissue?

Answer 31

Increases heart rate and cardiac output Promotes synthesis of cardiac Beta-adrenergic receptors making the cardiac tissue more sensitive to sympathetic innervation

Question 32

What is the pathophysiology of hyperthyroidism?

Answer 32

Metabolism: - Heat intolerance - Weight loss - Increased BMR Bone: - Osteoperosis CNS: - Agitation - Anxiety - Difficulty concentrating - Hyperreflexia Skin: - Sweating CV System: - Tachycardia - Atrial Fibrulation - Palpitations - High-output cardiac failure Intestine: - Diarrhea

Question 33

What is the pathophysiology of hypothyroidism?

Answer 33

Metabolism: - Cold intolerance - Weight gain - Decreased BMR Bone: - Stunted growth CNS: - Slowed movement - Impaired memory - Decreased mental capacity Skin: - Dry CV System: - Bradycardia - Decreased contractility - Decreased cardiac output Heart Failure Intestine: - Constipation

Question 34

What is Primary Hyperparathyroidism vs Secondary Hyperthyroidism?

Answer 34

Primary = Graves Disease - Excessive secretion of TH from the thyroid gland (TSH levels will be decreased due to negative feedback) Secondary = Excessive secretion of TSH from the anterior pituitary gland

Question 35

What is Grave's Disease?

Answer 35

Thyroid Stimulating Immunoglobulins (TSIs) that are analogous to TSH will stimulate the TSH receptor on the thyroid gland promoting synthesis and secretion of TH despite lack of actual TSH signaling from the anterior pituitary gland Major clinical signs: - Exophthalmos (protrusion of eyeball) - Periorbital edema

Question 36

What is Sheehan's syndrome?

Answer 36

Hypothyroidism due to pituitary necrosis secondary to blood loss during or after delivery of baby (no TSH secretion from anterior pituitary, and therefore no TH secretion from thyroid gland)

Question 37

How do you treat hypothyroidism?

Answer 37

T4 supplementation In older women, over prescribing T4 supplements can cause osteoporosis

Question 38

What is Hashimoto's Thyroiditis?

Answer 38

Autoimmune disorder Antibodies produced to fight against Thyroglobulin protein in colloid or Thyroid Peroxidase enzyme Prevents synthesis of Thyroid hormone Excessive TSH secretion occurs, causing production of a goiter

Question 39

What is cretinism?

Answer 39

Cretinism is congenital hypothyroidism Caused by iodine deficiency, impaired development of thyroid gland Symptoms: - Mental retardation - Growth retardation - Dry skin - Protruding tongue - Respiratory difficulty - Feeding problems

Question 40

What causes goiters?

Answer 40

TSH receptor activation causes hypertrophy of thyroid gland (goiter) Anyway TSH receptor is activated excessively will cause a goiter, whether or not it is TSH that is activating it (Graves disease causes goiter even though it is an Immunoglobulin that activates the TSH receptor, not actual TSH)