Thyroid and Anti-thyroid Drugs

Question 1

Describe the steps of TH synthesis beginning with import of iodide through release of hormone.

Answer 1

Iodide is imported into the follicular epithelium through the NIS. Once inside, Iodide is oxidized by peroxidase to iodine, which is exported in to the colloid through pendrin. In the colloid tyrosine residues of TG are iodinated to form MITs and DITs. DITs and MIT will couple to form T3 and T4. All four products are release from the colloid by exocytosis and proteolysis. MITs and DITs are recycled after deiodination.

Question 2

What are the two steps in TH production which are inhibited by high iodine levels?

Answer 2

Iodination and Proteolysis

Question 3

What is the difference between T3 and rT3?

Answer 3

Deiodination of the outer and inner rings, respectively.

Question 4

Describe T3 and T4 for with reference to bioavailability, half-life, and clearance.

Answer 4

Biovailability: T3 is 95% and T4 is 80%
Half-life: T3 is 1 day and T4 is 7 days
Clearance of both increases in hyperthroidism, and decreases in hypothyroidism.

Question 5

What are the four types of agents which effect thyroid function?

Answer 5

1. Inhibit the conversion of T4 to T3
2. Increase hepatic metabolism
3. Interferes with T4 absorption
4. Induces auto-immune thyroid disease

Question 6

Name the 5 agents which interfere with T4 to T3 conversion.

Answer 6

1. Radiocontrast
2. Amiodarone
3. Beta-Blockers
4. Corticosteroids
5. Propylthiouracil

Question 7

Name the 5 agents which increase hepatic metabolism.

Answer 7

1. Rifampin
2. Phenobarbital
3. Carbemazepine
4. Phenytoin
5. HIV Protease Inhibitors

Question 8

Name the 8 agents which decrease T4 absorption.

Answer 8

1. Bisphosphonates
2. Bile Acid Sequestrants (Cholestyramine)
3. Ciprofloxacin
4. PPIs
5. Sucralfate
6. Bran
7. Soy
8. Coffee

Question 9

Name the 4 agents which induce autoimmune thyroid disease (Graves or Hashimoto)

Answer 9

IFN-alpha, IFN-beta, lithium, or amiodarone

Question 10

What is levothyroxine the DOC for?

Answer 10

Replacement and suppression therapies

Question 11

What is liothyronine the DOC for?

Answer 11

Short-term suppression of TSH

Question 12

What are the ADRs of liothyronine?

Answer 12

Increased risk of cardiotoxicity

Question 13

Describe thioamides with respect to prototypes (2), MOA, and onset of action.

Answer 13

Prototypes = methimazole and propylthiouracil

MOA = inhibition of peroxidase catalyzed reactions, iodine organification, and coupling. PTU also prevents peripheral deiodination.

Onset of Action = Slow; 3-4 weeks

Question 14

What is methimazole the DOC for?

Answer 14

Most cases requiring anti-thyroid medication

Question 15

What is propylthiouracil the DOC for, and why?

Answer 15

Antithyroid therapy in the 1st trimester of pregancy. Both drugs cross the placenta, but PTU is more strongly protien bound.

Question 16

Discuss ADRs (7) related to thioamides. Also, which are specific to methimazole and PTU. Identify the most severe ADR.

Answer 16

Maculopapular rash, GI disturbances, vasculitis, Lupus-Like syndrome, hypoprothrombinemia, exfoliative dermatitis, acute arthralgia. Methimazole = cholestatic jaundice. PTU = severe hepatitis (leading to death). Most severe ADR is agranulocytosis.

Question 17

What is the MOA of Potassium Iodide?

Answer 17

Inhibits iodine organification and hormone release. Decrease size and vascularity of hyperplastic glands.

Question 18

What are three uses and two guidlines of potassium iodide therapy?

Answer 18

Uses = thyroid storm, preoperative reduction, and block radioactive iodine uptake

Guidlines

1. Never use alone. escape block within 3-8 weeks, and withdrawal can cause thyrotoxicosis.
2. Initiate after thioamide treatment.

Question 19

What are the ADRs of potassium iodide?

Answer 19

Acneiform rash, rinorrhea, metallic taste, bleeding disorders, anaphylaxis, and fetal goiters.

Question 20

Describe hypothyroid management with respect to DOC, exceptions, administration guidlines, and time of onset.

Answer 20

DOC = levothyroxine

Exceptions = If drug-induced hypothyroidism, discontinue medication.

Administration guidelines = 1 hour before meals, 4 hours after meals, or before bed. Administer at times separate from other drugs.

Onset = 6-8 weeks

Question 21

What are the manifestations of thyroxine toxicity in children, adults, and chronic over treatment?

Answer 21

Children - inosmnia, restlessness, and accelerated bone growth
Adults - hyperthyroidism
Chronically Treated - increased risk of atrial fibrillation and accelerated osteoporosis

Question 22

What are the Mx, Px, and Tx of myxdema coma

Answer 22

Mx - end-stage hypothyroidism. weakness, stupor, hypothermia, hypoglycemia, hypoventilation, hyponatremia

Px - Shock and Death

Tx - loading dose of thyroxine, followed by daily maintenance. Possibly cortisol for adrenal insufficiency.

Question 23

Describe the preferred patient population and treatment guidelines for antithyroid drugs.

Answer 23

Preferred Population - young with small glands and mild disease

Tx daily with methimazole until spontaneous remission. Long-course 18-21 months. High relapse rate.

Question 24

Describe the preferred population and treatment guidlines for thyroidectomy.

Answer 24

Preferred population - patients with large glands or MNG

Begin Tx with methimazole until euthyroid (6 weeks). 10-14 days before surgery, initiate potassium iodide for gland reduction.

Question 25

Describe the preferred population and treatment guidelines for Radioactive Iodine (RIA).

Answer 25

Preferred Population - over 21

Begin Tx immediately in those with out heart disease. Those with heart disease should be started on antithyroid medication until euthyroid, start RAI 5 days later, then antithyroid 5 days after RAI.

Question 26

Describe treatment of thyroid storm,

Answer 26

1. Beta-Blockers or CCBs
2. Potassium Iodide to prevent hormone release
3. PTU to prevent synthesis
4. Hydrocortison to prevent shock and peripheral deiodination.
5. Supportive therapy