Thyroid Pharmacology

Question 1

What are the relative half lives and potency of thyroid hormone?

Answer 1

T4: half life is 7 days
T3: half life is only 1 day but it is 4x more potent

Question 2

Are there greater levels of free T4 or free T3? About how much is there?

Answer 2

There is about 10x more free T3. Unbound T3 constitutes .4% of the total thyroid hormone

Question 3

What are the three classes of thyroid hormone preparations?

Answer 3

Levothyroxine: LT4
Liothyronine: LT3
T4/T3 Mixes: just don’t use them

Question 4

Why is hypothyroid treated with T4? (2)

Answer 4

Longer half life and peripheral conversion via deiodination

Question 5

When is T3 use indicated? (2)

Answer 5

Myxedema coma

Withdrawal for thyroid cancer radioactive iodine treatment

Question 6

When do you see side effects from thyroid treatment?

Answer 6

Only from inappropriate dosing

Question 7

What are some dosing considerations when starting therapy?

Answer 7

Starting dose depends on age, degree of thyroid failure of patient

Question 8

How often is TSH levels monitored?

What is the target range? Does this change for people of different ages?

Answer 8

Check TSH about every 6 weeks

Target TSH normal range (.5-5) with target usually below 2.5. The target is usually higher in older people

Question 9

What are reasons for TSH levels being higher than expected? (6)

Answer 9

Noncompliance
Drugs that decrease LT4 absorption
Conditions that decrease LT4 absorption: SI disease
Drugs that increase LT4 metabolism
Increased TBG
Progression of thyroid disease

Question 10

Name some drugs that increase LT4 metabolism.

Name some factors that increase TBG

Answer 10

Drugs: phenytoin, rifampin, phenobarbital, carbamazepine

Increased TBG seen during pregnancy, estrogens, hepatitis

Question 11

Why would TSH on therapy be lower than expected? (5)

Answer 11

Dopamine
High dose glucocorticoids
Decreased TBG
Self-administration of excess LT4
Reactivation of Grave's disease or development of autonomous nodules

Question 12

What are some factors that decrease TBG? (4)

Answer 12

Androgens
Nephrotic syndrome
Chronic liver disease
Severe systemic illness

Question 13

What are drugs that cause hypothyroidism? (5)

Answer 13

Primary: amiodarone, lithium, INFa, aminoglutethimide

Secondary bexarotene

Question 14

For what conditions should you involve a endocrinologist to monitor TSH levels? (2)

Answer 14

Pregnancy

Thyroid cancer

Question 15

What do you do to treat myxedema coma? Why?

Answer 15

First IV hydrocortisone to fix adrenal

Give LT4/LT3 IV–decreased metabolism for most medications

Question 16

What is the mechanism of antithyroid drugs?

Answer 16

interfere with two steps of thyroid hormone synthesis via TPO

1. Intrathyroidal iodine utilization
2. Iodotyrosine coupling

Question 17

When do you use antithyroid drugs?

Answer 17

Graves disease

To cool patient down prior to RAI or surgery

Question 18

What are two antithyroid drug? Which is preferred? Why? (3)

Answer 18

PTU and Methimazole.
Mithimazole has longer half life– longer duration of action.
Mithimazole is not protein bound.
PTU decreases T4-T3 conversion

Question 19

When do you use methimazole? When do you use PTU? (3)

Answer 19

Use methimazole in all Grave’s disease patients except:
First trimester of pregnancy
Thyroid storm
AE to methimazole

Question 20

What are the main side effects of antithyroid drugs? (6)

Answer 20

Agranulocytosis, severe hepatitis (just PTU), cholestasis (MMI), vasculitis, polyarthritis, skin rxns

Question 21

What is the greatest concern with antithyroid drugs?

How is it monitored?

Answer 21

Agranulocytosis, which occurs in .1-.5% patients at any time.

They should stop antithyroid drug and check WBC if fever or sore throat.

Question 22

Which drugs inhibit T4-T3 conversion? (3)

Answer 22

PTU
Glucocorticoids
Propanolol

Question 23

Which other drugs can you use in hyperthyroidism? (3)

Answer 23

Beta-blockers
NSAIDs in subacute thyroiditis
Iodine/glucocorticoids in severe thyrotoxicosis

Question 24

Which drugs do you use in treatment of Thyroid Storm? (4)

Answer 24

PTU
Propanolol or esmolol
Hydrocortisone
Potassium iodide drops

Question 25

How is iodide uptake mediated? How does it correspond to dietary supply?

Answer 25

Iodide uptake is mediated by the Na/I symporter (NIS). Low iodide increases NIS; high iodide decreases NIS

Question 26

Where is NIS expressed?

Answer 26

High levels in thyroid | Low levels in salivary glands, lactating breast, placenta

Question 27

What is optimal iodide intake? What are effects of prolonged decrease? (2)

Answer 27

Optimal intake is 100-150 mcg/day | Prolonged decrease results in endemic goiter and cretinism

Question 28

What is the Wolff-Chaikoff Effect? What is the clinical implication?

Answer 28

Excess iodide transiently inhibits thyroid iodide organification. In individual with normal thyroid, gland escapes inhibitory effect. But if underlying autoimmune thyroid disease, suppressive effect may persists.

Question 29

What is the Jod-Basedow Phenomenon? When is it observed?

Answer 29

The Jod-Basedow Phenomenon describes thyrotoxicosis produced by iodine exposure. It occurs in nodular thyroid glands

Question 30

Describe the uses for radioiodine. (2) When is it contraindicated

Answer 30

Can be used in low doses for diagnostic purposes or high doses for therapy It should not be given to breast-feeding/pregnant women or children

Question 31

When do you use radioiodine therapy? What is the long-term effect?

Answer 31

Use it in Grave's disease to create hypothyroidism. The result of radioiodine therapy is necrosis of follicular cells followed by disappearance of colloid and fibrosis of gland

Question 32

What is amiodarone?

Answer 32

Drug used to treat arrhythmias

Question 33

Describe the iodine effect of amiodarone: when do you observe it?

Answer 33

In patients with underlying thyroid nodular disease or Grave's disease, amiodarone results in increased thyroid hormone production. This is called the iodine effect

Question 34

Describe the direct toxic effect of amiodarone: when do you observe it?

Answer 34

In patients with normal thyroids it induces destructive thyroiditis--> There is increased release of preformed thyroid hormone from colloid

Question 35

When do you use recombinant TSH?

Answer 35

Use in thyroid cancer patients: stimulate thyroid tissue for diagnostic thyroglobulin measurement and radioiodine scanning. It avoids symptomatic hypothyroidism from radioiodine

Question 36

When does amiodarone cause hypothyroidism?

Answer 36

In patients with predisposition for hypothyroidism such as Hashimotos