Exam 1 - Treatment of Hyperthyroidism

Question 1

Which are the treatments for Hyperthyroidism

Answer 1

Propranolol
Thionamides (PTU, Methimazole)
Radioactive Iodine (RAI)
Anion Inhibitors (Perchlorate, Thiocyanate)
Iodides
Iodinated Contrast Media
Subtotal Thyroidectomy

Question 2

What are the characteristics of Propranolol?

Answer 2

● Helps reduce peripheral manifestations (tachycardia, sweating, tremor, nervousness)
● β­blocker which also inhibits the peripheral conversion of T4 to more potent T3 form by inhibiting 5’­deiodinase

Question 3

What are the characteristics of Thionamides (PTU, Methimazole)?

Answer 3

● MOA: inhibit iodine oxidation and iodotyrosyl coupling → bind to and inhibit thyroid peroxidase
● Onset of action is delayed until previously­ formed T3 and T4 stored in the thyroglobulin colloid is depleted
● Adverse effects: agranulocytosis – rare (bone marrow depression – can’t make WBCs), dermatological reactions
● Use PTU for thyroid storm inhibits conversion of T4 to T3 while methimazole does not
● Methimazole (Tapazole®) 10x more potent and longer t 1/2 than PTU
● See response onset in 3­4 weeks (or more)
● Black box warning for PTU for liver failure

Question 4

What are the characteristics of Anion Inhibitors (Perchlorate, Thiocyanate)?

Answer 4

● Compete with I­- for uptake into thyroid
● Use of perchlorate has been associated with
aplastic anemia (lower doses are used than in the past)
● Perchlorate is 10 x more potent than thiocyanate

Question 5

What are the characteristics of Radioactive Iodine (RAI)?

Answer 5

● Radioactive I131 destroys cells by β­particle emission to decrease thyroid hormone production (usual dose is sufficient to destroy most (or all) of the thyroid hormone­ producing cells of the gland)
● High cure rate (almost 100%)
● Avoid surgical risks (good!)
● See response in 3­6 months
● Contraindicated in pregnancy (will ablate fetal thyroid)
● Hypothyroidism (expected) occurs in 78% with Graves’ disease and 40% of those with Plummer’s disease (requires lifetime treatment with exogenous thyroid hormones). Sometimes the hypothyroisim takes years to develop (i.e delayed hypothyroidism)

Question 6

What are the characteristics of Iodides?

Answer 6

● Fastest­ acting anti­thyroid effect (2-7 days) → use in thyroid storm
● Inhibits organification of I- (i.e. acute Wolff-Chaikoff effect): lasts only 2-­10 days → effect depends on first achieving high intrathyroidal levels of iodide → inhibits transcription of TPO and NADPH oxidase (the enzyme that provides H2O2 to TPO for the oxidation of iodide ion) → escape from this effect is due to the ability of iodides to eventually inhibit the transcription of the NIS. Less uptake of iodides then reduces intrathyroidal levels below a critical threshold for the inhibition of organification
● Major mechanism of action is to Inhibit thyroid hormone release at high serum levels (hydrolysis of T4 and T3 from thyroglobulin is inhibited). Iodides lose this antithyroid effect in 2-­8 weeks = (iodide “escape”)
● Despite the above two actions, administration of these high doses of iodides is associated initially with an increase in intrathryroidal stores of iodide which will be used to make T3 and T4! Therefore, don’t use iodides as monotherapy! → Should administer thionamides before commencing iodide therapy since this will prevent formation of T3 and T4

Question 7

What are the characteristics of Iodinated Contrast Media?

Answer 7

● Rapidly inhibits conversion of T4 to T3 in the liver, kidney, pituitary gland and brain
● Iodide release from these contrast media produce high I­ levels (and hence inhibition of T3 and T4 proteolysis from thyroglobulin) may be another mechanism
● Uses: treatment of thyroid storm

Question 8

What are the characteristics of Subtotal Thyroidectomy?

Answer 8

● Partial removal of the thyroid gland (used when thyroid therapy fails or radioactive iodine is undesirable)
● Difficult procedure, but high success rate

Question 9

Which are the iodides?

Answer 9

● Lugol’s solution and saturated solution of potassium iodide (SSKI)

Question 10

Which are the Thionamides?

Answer 10

PTU and Methimazole

Question 11

Which are the Anion Inhibitors?

Answer 11

Perchlorate and Thiocyanate

Question 12

What are the uses of thionamides?

Answer 12

• As definitive treatment to control the disorder in anticipation of a spontaneous remission in Graves’ disease
• ­In conjunction with radioactive iodine, to hasten recovery while awaiting the effects of radiation
  ­- To control the disorder in preparation for surgical treatment