Thyroid and Antithyroid Drugs

Question 1

Synthesis and Transport of Thyroid Hormones

Answer 1

TRANSPORT
iodide ion is converted to iodine by thyroid peroxidase (TPO)

IODINE ORGANIFICATION
tyrosine residues in thyroglobulin are iodinated to form monoiodotyrosine (MIT) or diiodotyrosine (DIT)

COUPLING
2 molecules of DIT to form T4
1 molecule of each MIT and DIT to form T3

PROTEOLYSIS
T4 and T3 released from the thyroid and transported in the blood by thyroxine binding globulin (TBG)

Question 2

Thyroid Hormones for Hypothyroidism

maximum effect seen after 6-8 weeks of therapy

Answer 2

Levothyroxine - T4
Liothyronine - T3
Liotrix and Thyroid USP - 4:1
Thyroglobulin - 2:1

Question 3

Medical emergency representing the end state of untreated hypothyroidism

progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock and death

Answer 3

Myxedema Coma

TREATMENT:

Levothyroxine - 300 -400 mcg followed by 50-100 mcg daily

Question 4

Treatment of Myxedema Coma

Answer 4

IV loading dose of Levothyroxine (300 - 400 mcg) followed by 50-100 mcg daily

IV hydrocortisone - if patient has associated adrenal or pituitary insufficiency

Question 5

Inhibits thyroid peroxidase reactions

Blocks iodine organification

(-) peripheral conversion of T4 into T3

Answer 5

THIOAMIDES

Propylthiouracil

Question 6

Side effects of Propylthiouracil

Answer 6

maculopapular pruritic rash
FULMINANT HEPATITIS
AGRANULOCYTOSIS
Lupus like syndrome

Question 7

Inhibits thyroid peroxidase reactions

Blocks iodine organification

Answer 7

THIOAMIDES

Methimazole
Carbimazole

Question 8

Preferable during the 1st trimester of pregnancy, thyroid storm and those experiencing adverse reactions to methimazole

Answer 8

Propylthiouracil

Question 9

DOC for nonpregnant hyperthyroid px because of longer DOA (24 h)

Answer 9

Methimazole

Question 10

Side effects of Methimazole

Answer 10

aplasia cutis congenita
choanal atresia
esophageal atresia

Question 11

The mainstay of the treatment of postpartum hyperthyroidism in particular during lactation

Answer 11

Methimazole

Question 12

Acute severe neutropenia
Heralded by SORE THROAT or HIGH FEVER
Increased susceptibility to infections

Answer 12

AGRANULOCYTOSIS

discontinue PTU or methimazole
administer recombinant G-CSF (Filgrastin) to accelerate recovery
treat w/ prophylactic broad-spectrum antibiotics

Question 13

(-) iodide uptake (trapping)

Answer 13

INORGANIC ANIONS

K Perchlorate
K Thiocyanate

HIGHLY TOXIC

Question 14

(-) iodine organification and hormone release

reduce size and vascularity of thyroid gland

improvement in thyrotoxic symptoms occurs rapidly - 2-7 days

Answer 14

IODIDE

Lugol’s solution
Potassium Iodide
Potassium Iodide Saturated Solution (KISS)

Question 15

Side effects of Iodides

Answer 15

iodinism
acneiform rash
metallic tase

Question 16

Ingestion of IODINE causes HYPOthyroidism

Answer 16

Wolf-Chaikoff effect

Question 17

Ingestion of IODINE causes HYPERthyroidism

Answer 17

Jod-Basedow effect

Question 18

(-) peripheral conversion

(-) deiodinase

(-) proteolysis

Answer 18

RADIOCONTRAST DYES

Ipodate
Iopanoic Acid

Question 19

control HR and other cardiac abnormalities of severe thyrotoxicosis

(-) peripheral conversion of T4 into T3

cause clinical improvement WITHOUT altering thyroid hormone levels

Answer 19

BETA BLOCKERS

Propranolol
Esmolol
Metoprolol
Atenolol

Question 20

May be used to treat thyrotoxicosis-related arrhythmias

Answer 20

Esmolol

Question 21

Emits beta rays causing destruction of thyroid parenchyma

Patients should be EUTHYROID or on BETA BLOCKERS before RAI

Onset of action - 6-12 weeks
Maximum effect - 3-6 mos

Answer 21

Radioactive Iodine 131

Question 22

Preferred treatment for most patients

Permanent cure of thyrotoxicosis w/o surgery and no effect on other tissues

Answer 22

Radioactive Iodine 131

Question 23

Sudden acute exacerbation of all of the symptoms of thyrotoxicosis presenting as a life threatening syndrome

Answer 23

Thyroid Storm

Question 24

Treatment for Thyroid Storm

Answer 24

Propylthiouracil (PTU) - blocks thyroid hormone synthesis

Iodides (SSKI) - retards release of thyroid hormones

Propranolol - controls severe cardiovascular manifestations

Hydrocortisone - protects against shock and also blocks peripheral conversion of T4-T3

Question 25

Drugs that can cause drug-induced hyperthyroidism

Answer 25

CAM

Clofibrate
Amiodarone
Methadone

Question 26

Amiodarone-Induced Thyroid Disease

Answer 26

hypothyroidism - block the peripheral conversion of T4-T3
Tx: LEVOTHYROXINE

hyperthyroidism through iodine induced mechanism in persons w/ underlying thyroid disease or through an inflammatory mechanism that causes leakage of thyroid hormone
Tx: THIOAMIDES or CORTICOSTEROIDS

Question 27

SE of Radioactive Iodine (I131)

Answer 27

hypothyroidism (permanent)
sore throat
sialadenitis

associated with radiation exposure: PAPILLARY THYROID CA

Question 28

Acute severe neutropenia <500 cells/mm3

Heralded by SORE THROAT or HIGH FEVER

Answer 28

AGRANULOCYTOSIS

discontinue PTU or methimazole

administer recombinant G-CSF to accelerate recovery (Filgrastin)

treat with prophylactic broad-spectrum antibiotics

Question 29

Treatment of Thyroid Storm

Answer 29

PTU - blocks thyroid hormone synthesis

Iodides - retards release of thyroid hormones
*always administer PTU before iodides

Propranolol

Hydrocortisone - protects against shock

Question 30

Drugs that (-) conversion of T4-T3

Answer 30

PTU
Propranolol
Hydrocortisone

Question 31

Drugs that can cause DRUG INDUCED HYPERTHYROIDISM

Answer 31

CAM

Clofibrate
Amiodarone
Methadone