Thyroid and antithyroid agents

Question 1

where does thyroid hormone synthesis take place?

Answer 1

cell itself and colloid

Question 2

how does iodide get into the thyroid gland?

Answer 2

sodium / iodide symporter (NIS)

Question 3

what enzyme is responsible for converting iodide to iodine?

Answer 3

peroxidase

Question 4

what is iodide organification? what are the results?

Answer 4

iodination of tyrosine residues within thyroglobulin molecule

monoiodotyrosine (MIT)
diiodotyrosine (DIT)

Question 5

how are the thyroid hormones formed?

Answer 5

molecules of MIT and DIT are combined to form:

MIT plus DIT - T3
DIT plus DIT - T4

Question 6

what is the typical ratio of thyroid hormones?

Answer 6

T4: T3 - 5:1

Question 7

the majority of thyroid hormones are bound to what molecule?

Answer 7

thyroxine bound globulin (TBG)

Question 8

what is the MOA of thyroid hormone in the absence of thyroid hormone?

Answer 8

homodimer of receptor is sitting on response element of gene - NO activation of transcriptional processes

Question 9

what is the MOA of thyroid hormone in presence of thyroid hormone?

Answer 9

hormone is transported into cell

RXR and TR form heterodimer and increases gene transcription

Question 10

what is the function of 5’-deiodinase (5’-DI)?

Answer 10

conversion of T4 to T3

Question 11

what is the result of inhibition of 5’-DI?

Answer 11

hypothyroidism type symptoms

Question 12

what is the regulation of thyroid secretion? what type of feedback is involved?

Answer 12

TRH - TSH

TSH promotes synthesis of T4 and T3

negative feedback

Question 13

what are the result of high blood concentrations of iodide on hormone synthesis? low blood levels?

Answer 13

inhibition

promotion of synthesis

Question 14

what are the metabolic effects of thyroid hormone on fat?

Answer 14

1. decrease circulating cholesterol via increase in LDLr expression
2. increased lipolysis

Question 15

what are the metabolic effects of thyroid hormone on carbohydrates?

Answer 15

1. increased intestinal absorption of carbohydrates
2. increased glycolysis
3. increased gluconeogenesis
4. increased insulin secretion

Question 16

what are the metabolic effects of thyroid hormone on protein?

Answer 16

increased protein synthesis and catabolism

Question 17

what are the metabolic effects of thyroid hormone on vitamins?

Answer 17

increase need and usage for cofactors to enzymes as a result of a general increase in enzyme secretion

Question 18

definition: myxedema

when is it seen in relation to thyroid metabolism?

Answer 18

puffy, baggy eyes from retention of fluids in interstitial spaces

hypothyroidism

Question 19

what are the causes of hypothyroidism?

Answer 19

congenital 
autoimmune thyroiditis (hashimoto's) 
iodide deficiency

Question 20

what are the treatment options for hypothyroidism?

Answer 20

levothyroxine (T4)
liothyronine (T3)
liotrix (mixture T3 and T4)

Question 21

what is the treatment of choice for hypothyroidism? why?

Answer 21

levothyroxine

more stable, low cost, long half life, more physiological

Question 22

what is the MOA of thyroid hormone?

Answer 22

activation of T3 receptors

Question 23

what considerations should be made when treating elderly patients for hypothyroidism? why?

Answer 23

must check for underlying CV disease (decreasing contractility and BP)

hypothyroidism is protective for potential coronary artery disease

Question 24

what are the adverse effects of thyroid hormone in children?

Answer 24

restlessness, insomnia, accelerated bone maturation

Question 25

what are the adverse effects of thyroid hormone in adults?

Answer 25

nervousness, heat intolerance, palpitations, tachycardia, weight loss

Question 26

which thyroid hormone is more potent? why?

Answer 26

T3 already in ligand-active form

Question 27

what is the mechanism of grave's disease? what are the levels of TSH?

Answer 27

autoantibodies stimulate TSH receptors and increase the production of T3 and T4 TSH levels will be low

Question 28

what are the thioamide antithyroid agents for hyperthyroidism?

Answer 28

methimazole | propylthiouracil (PTU)

Question 29

what is the MOA of the antithyroid agents?

Answer 29

inhibition of peroxidase reaction, iodineorganification, and coupling of iodotyrosines

Question 30

which antithyroid agent is appropriate for use in pregnant women? why?

Answer 30

propylthiouracil (PTU) 75% protein binding

Question 31

what is the significant adverse effect of PTU?

Answer 31

severe hepatitis

Question 32

what are the iodide antithyroid agents?

Answer 32

potassium iodide | lugol's solution

Question 33

what is the MOA of the iodide antithyroid agents?

Answer 33

1. inhibition of TGB proteolysis | 2. decreases vascularity, size, and fragility of hyperplastic gland

Question 34

which class of antithyroid agents are useful against iodide storm? why?

Answer 34

iodide agents rapid onset

Question 35

which class of antithyroid agents are useful for hyperplastic gland and preop preparation? why?

Answer 35

iodide agents decreases vascularity, size, and fragility of hyperplastic gland

Question 36

what is the radioactive antithyroid agent? what is the MOA?

Answer 36

radioative iodine 131-I destruction of parenchymal cells

Question 37

what are the anion inhibitor antithyroid agents?

Answer 37

perchlorate pertechenate thiocyanate

Question 38

what is the MOA of the anion inhibitor antithyroid agents?

Answer 38

inhibition of energy dependent uptake of iodide into the thyroid cells that is mediated by sodium / iodide symporter

Question 39

what is the main adverse effect of radioactive iodine 131-I?

Answer 39

hypothyroidism

Question 40

what agents can be used to treat iodide-induced hyperthyroidism (eg amiodarone induced thyrotoxicosis)

Answer 40

anion inhibitors

Question 41

what are the key adjuncts antithyroid agents?

Answer 41

propanolol diltiazem barbiturates bile acid sequestrants

Question 42

what are the clinical uses of beta blockers for hyperthyroidism?

Answer 42

adjunct to control tachycardia, HTN, aF

Question 43

what is the clinical use for diltiazem?

Answer 43

control tachycardia in asthmatic

Question 44

what is the clinical use for barbiturates?

Answer 44

increase T4 metabolism

Question 45

what is the clinical use for bile acid sequestrants?

Answer 45

increase biliary T4 excretion