Pharmacology of Thyroid Disorders

Question 1

What is the mechanism of amiodarone’s causing of hypo and hyperthyroidism, other than its iodine loading efffect?

Answer 1

Hypothyroid:

1. Reduces peripheral conversion of T4 to T3
2. Blocks T3 nuclear receptor

Direct toxic effect on thyroid follicular cells -> destructive thyroiditis -> transient hyperthyroid followed by hypothyroid

Question 2

What is the dose-limiting side effect of levothyroxine therapy, and what is the general treatment paradigm for elderly patients?

Answer 2

Dose-limiting: Cardiac symptoms, i.e. tachycardia, AFib, risk of cardiac mortality

Treatment paradigm: Stat at a low dose and titrate up slowly (drug has a long halflife, don’t want to overdo it)

Question 3

What are the problems with using natural iodine purified from pig/cow/sheep?

Answer 3

1. Antigenic potential - change to become allergic
2. Unstable bioavailability
3. Unknown dosing / inconsistent

Question 4

How long does it take levothyroxine to reach steady state? How often should you re-evaluate once symptoms are resolved? How does T4 clearance change as you age?

Answer 4

About 6-8 weeks

Should re-evaluate every 6-12 months once euthyroid

T4 clearance decreases as you age -> need lower dose in elderly

Question 5

What is the most sensitive test of thyroid function overall?

Answer 5

TSH -> responds massively to small changes in T3/T4

Free T4 can also be measured.

Question 6

When should you take levothyroxine and what should you avoid taking at the same time?

Answer 6

Take at least 30-60 minutes before breakfast, or 4 hours after the last meal

• > need to not interfere with its absorption
• > avoid iron-containing products, calcium-containing products which avidly bind thyroxine and reduce absorption

Question 7

What drugs interact with levothyroxine concentrations overall?

Answer 7

Estrogens -> increase TBG
CYP Enzyme inducers -> increase clearance
Resin binders -> i.e. cholestyramine
Aluminum-containing compounds -> Aluminum hydroxide, sucralfate

Question 8

What should you do if a patient changes brands of levothyroxine?

Answer 8

Re-assess thyroid function in 6-8 weeks -> certain brands can be a little off and fuck with your levels

Question 9

What is the clinical definition of subclinical hyperthyroidism and what is the cause? Should you treat it?

Answer 9

Low TSH but normal free T4, asymptomatic

Normal cause is too much levothyroxine

Fix the levothyroxine dose

Question 10

What is the clinical definition of subclinical hypothyroidism? Should you treat it?

Answer 10

High TSH but normal T4, asymptomatic

Should not be treated

Question 11

What is the treatment for myxedema coma and why?

Answer 11

1. IV bolus thyroxine - obviously

2. IV hydrocortisone - adrenal suppression presents similarly, and you want to treat for that too just in case.

Question 12

What drugs inhibit thyroperoxidase and which one is different / how is it different?

Answer 12

Methimazole (MMI)

Propylthiouracil (PTU)
-> also useful in thyroid storm by inhibiting 5’ deiodinase.

Question 13

Which of the two thioamides is preferred and why?

Answer 13

Methimazole, because it has a lower risk of hepatotoxicity. It also has a longer halflife for convenient once-daily dosing.

Question 14

What are the adverse effects of PTU and MMI?

Answer 14

Maculopapular rash - think of the dude with a rash
Lupus-like syndrome - MMI specifically, think of the lupus wolf
Aplastic anemia - blue bones on ground
Agranulocytosis - hourglass in back
Hepatotoxicity - especially PTU

Question 15

What should one do if PTU or MMI causes hepatotoxicity, agranulocytosis, or benign transient leukopenia (WBC<4000)?

Answer 15

Hepatotoxicity - don’t switch to the other agent! they are cross-reactive
Agranulocytosis - don’t switch to the other agent! they are cross-reactive
Benign transient leukopenia - no one cares, continue onward

Question 16

What is the preferred pregnancy regimen for hyperthyroid patients and why?

Answer 16

1st trimester: PTU, since methimazole is a teratogen (think of the tarantula) -> cause cutis aplasia

2nd/3rd trimesters: Use MMI since PTU is more hepatotoxic

Question 17

What is the drug of choice for toxic autonomous nodules, multinodular goiters, the elderly, and those with cardiac disease in hyperthyroidism?

Answer 17

Radioactive iodine (I-131)

Question 18

What is the drug of choice for hyperthyroidism for poor surgical candidates or those for whom thioamides (PTU/MMI) failed?

Answer 18

Radioactive iodine (I-131)

lul

Question 19

What is the mechanism of action of Radioactive iodine and what are the contraindications?

Answer 19

Mechanism: Disrupts hormone synthesis, causes cellular necrosis and follicular breakdown
-> generally only need one treatment, can repeat at 6 months

Contraindications: pregnancy (hypothyroid of fetus), breastfeeding, children

Question 20

What monitoring should be done after radioactive iodine ablation?

Answer 20

Monitor thyroid function tests every 3 months for a year

Look for signs of hypothyroidism -> most common side effect

Question 21

What drugs are given pre and post thyroid surgery for malignancy to prevent thyrotoxicosis symptoms?

Answer 21

Pre:

Thionamides for 6-8 weeks until euthyroid

Iodide therapy - 10-14 days pre-op to reduce size and vascularity of thyroid gland

Post:
Propranolol - incase some cell lysis occurred

Question 22

What adjunctive rate control agent is commonly given if beta blockers are contraindicated in hyperthyroidism?

Answer 22

Verapamil or diltiazem

Question 23

What are some precipitating factors of thyroid storm?

Answer 23

Infection, trauma, or surgery

Question 24

What is the definition of agranulocytosis with MMI or PTU treatment? How will the patient present to you? What should you do?

Answer 24

Absolute neutrophil count <500 / microL

Patient will present with signs of infection: Fevere, sore throat, malaise, erythematous stomatitis, unusual bleeding / bruising

You should order a WBC with differential to see if agranulocytosis is the cause of their symptoms