Thyroid/Antithyroid Agents

Question 1

How do TSH and methimazole affect the thyroid hormone synthesis pathway?

Answer 1

Methimazole: this is an antithyroid agent that blocks the transport of iodide

TSH: stimulates all steps involved in T4 synthesis pathway

Question 2

What are the roles of TSH, TRH, iodine, and antibodies to TSH receptors in the regulation of thyroid hormone secretion?

Answer 2

TSH: Stimulates all steps involved in T2 synthesis pathway

TRH: Stimulates the release of TSH and prolactin by anterior pituitary

Iodide: Needed for synthesis

TSH-R(AB): activates TSH receptors, which increases T3 and T4 secretion and causes hyperthyroidism (Humans)

Question 3

What effects do different stressor (ie cold) have on thyroid hormone secretion?

Answer 3

Increased TRH = Increased TSH = Increased T4

Question 4

What are the three major carriers of T3 and T4 in circulation?

Answer 4

Thyroxine binding globulin: high affinity low capacity
Prealbumin
Albumin

Question 5

T/F Throxine binding globulin is 4x higher in humans than it is in dogs and is not found in cats, rabbits, or birds

Answer 5

TRUE

Question 6

What do cats, rabbits, and birds use to bind T3 and T4?

Answer 6

Transthyretin (Prealbumin)

Question 7

In humans, what % of T4 and T3 is bound by plasma proteins. Is this higher or lower in dogs?

Answer 7

T4 = 99.98%

T3 = 99.8%

Dogs = lower, about 99%

Question 8

T/F when treating a dog with hypothyroidism, a human dose will usually treat them

Answer 8

FALSE

Question 9

Why can you not treat dogs with hypothyroidism with human levels of T4?

Answer 9

It is too low; the half life of T4 in dogs is 8-16 hours, while it is 7 days in humans

Question 10

How are thyroid hormones excreted/

Answer 10

Conjugates enter the bile and into the gut where they are removed via feces

Question 11

What are some factors that can affect plasma protein levels and binding?

Answer 11

Estrogen = Increase TBG synthesis
Liver and kidney dz = decreased half-life
NSADIS and CNS drugs = competition for albumin binding sites to free T3 and T4

Question 12

What is the fate of most of the T4 in the system?

Answer 12

50% –> rT3
30-40% –> T3
15-20% –> Conjugates in liver

Question 13

Where is Type I deiodinase found?

Answer 13

Liver and kidney

Transformation from T3 and T4

Question 14

Where is Type II deiodinase found? What does it do?

Answer 14

Deiodinates T4

Brain, pituitary, and brown fat

Question 15

Where is Type 3 deiodinase found and why is it important?

Answer 15

Placenta and brain

Fetus is surrounded by the placenta. Fetus has a lot of T3 so it is a way to control it and save the mom

Question 16

What increases the rate of T4 to T3 conversion?

Answer 16

Hypothyroidism

Hyperthyroidism causes a decreased rate of T4 –> T3

Question 17

What is the current perspective regarding the cold temperature on calorigenesis?

Answer 17

Cold > increased EPI, NE > increased Type 2 deiodinase > increased T3 > increased uncoupling protein in mitochondria > generates heat

Question 18

Where are a large number of mitochondria with uncoupling proteins located?

Answer 18

Brown fat cells; located between scapulas, in thorax, and abdomen

Question 19

What is the action of thyroid hormones on growth and development?

Answer 19

Increases GH secretion and action; shortage of this can lead to cretinism.

Critical for development and maintenance of neural tissues

Question 20

What is the action of thyroid hormones on calorigenesis?

Answer 20

Increase in heat generation and oxygen consumption

Question 21

What is the action of thyroid hormones on CV system?

Answer 21

Increased CO needed to keep up with an increased oxygen consumption

Question 22

What is the action of thyroid hormone on lipid metabolism?

Answer 22

Facilitation of the effect of the lipolytic hormones

Increased conversion into bile acids

Question 23

What dermatologic effects does the thyroid hormones have?

Answer 23

They are needed for hair and skin turnover

See alopecia in hyperthyroidism

Question 24

What effects does thyroid hormone have on the neuromuscular gland?

Answer 24

Increased synthesis of proteins associated with nueromuscular activity

Question 25

What effects does thyroid hormone have on GI and repro system?

Answer 25

Needed for normal GI motility and reproduction

Question 26

What are some clinical signs of hyperthyroidism/

Answer 26

Weight loss in spite of ravenous appetite, hyperactivity, PU/PD, diarrhea, vomiting, tachycardia, and hair loss

Question 27

What are some clinical signs of hypothyroidism?

Answer 27

Lethargy, weakness, coma, obesity, cold intolerance, skin lesions, infertility, number 2 underlying cause of demodicosis

Question 28

Why is T4 preferred over T3 for treatment of hypothyroidism?

Answer 28

T4 has a longer half life and giving T4 as replacement therapy will get plenty of T3 generated in the brain anyway

Question 29

How does 131-I work as an antithyroid agent in hyperthyroidism?

Answer 29

It is a beta-R antagonist everywhere, especially the thyroid

This is used for non-surgical thyroidectomy

Question 30

Which group of antithyroid drugs is preferred in the control of hyperthyroidism?

Answer 30

Methimazole

Question 31

What is Methimazole’s method of action

Answer 31

Blocks iodide transport

Question 32

What are some adverse effects of Methimazole?

Answer 32

Anorexia, vomiting, lethargy, eosinophilia, severe scratching, and hepatopathy

Question 33

Cetecholamines devastate hyperthyroid myocardium. What drug can be used to counteract this?

Answer 33

Beta-blockers: Propanolol and atenalol