Pharm - Thyroid

Question 1

[Men/Women] are more likely to suffer from a thyroid condition

Answer 1

Women – 5-8x more likely

Question 2

[Younger/Older] are more likely to suffer from hypothyroidism

Answer 2

Older – 17% of women by age 60 have hypothyroid conditions

Question 3

What is the active metabolite form of thyroid hormone?

Answer 3

T3

Question 4

What is the pro-hormone form of thyroid hormone?

Answer 4

T4 – Thyroxine

Question 5

Where are the 3 deiodinases (D1, D2, D3) expressed?

Answer 5

D1 = liver, kidney
D2 = CNS, pituitary, thyroid, heart, brown fat, skele muscle
D3 = brain, skin, placenta, tissue in disease states (tumors)

Question 6

Which deiodinase has inactivating function?

Answer 6

D3 – inactivates T3 by converting to T2 and reverse T3

Question 7

Which deiodinase contributes the most to circulating T3?

Answer 7

D2 – contributes ~60% of T3 converted from T4

—-D1 only contributes ~ 24%

Question 8

What happens in Hashimoto’s Thyroiditis?

Answer 8

Autoantibodies against symporter affecting iodide transport

Question 9

High TSH, Low T4

What thyroid state?

Answer 9

Primary Hypothyroidism – No feedback inhibition of TSH production

Question 10

Low TSH, Low T4

What thyroid state?

Answer 10

Secondary Hypothyroidism – low TSH made in anterior pituitary is primary cause, leading to no T4 made in thyroid

Question 11

Low TSH, High T4

What thyroid state?

Answer 11

Hyperthyroidism – Thyroid uses up normally made amounts of TSH to make lots of T4

Question 12

Associated w/ [hyper/hypo] thyroidism:

• -Goiter
• -Cold Sensitivity
• -Heat Intolerance
• -Exopthalmos
• -Excessive sweating
• -Tachycardia
• -Constipation
• -Weight gain
• -Dry/brittle hair

Answer 12

• -Goiter = HypO
• -Cold Sensitivity = HypO
• -Heat Intolerance = HypER
• -Exopthalmos = HypER
• -Excessive sweating = HypER
• -Tachycardia = HypER
• -Constipation = HypO
• -Weight gain = HypO
• -Dry/brittle hair = HypO

Question 13

How is most circulating T3 generated?

Answer 13

Peripheral conversion from T4 (80%) – 20% is direct secretion

Question 14

Adult onset (especially older women) severe form of hypothyroidism is called ___

Answer 14

Myxedema

Question 15

Infant/childhood hypothyroidism that causes mental retardation and Dwarfism is called ___

Answer 15

Cretinism

Question 16

The first synthetic thyroid hormone is called ___ and is specifically the ___ form.

Answer 16

Levothyroxine Sodium – T4 replacement

Question 17

T3 form synthetic thyroid hormone is called ___

Answer 17

Liothyronine Sodium

Question 18

Synthetic thyroid hormone that is a mixture of T3/T4 called ___ has more ___ form by weight.

Answer 18

Liotrix —4:1 ratio of T4:T3

Question 19

Patients with what condition have difficulty converting T4 to T3?

Answer 19

Chronic Fatigue Syndrome

Question 20

In what patient population should Levothyroxine be initiated with lower doses?

Answer 20

Patients w/ Angina Pectoris

Question 21

Half life and time to peak theraputic effect of Levothyroxine?

Answer 21

Half life = 6-7days
Time to Peak theraputic = 3-4weeks
Longer half life compared to Liothyronine

Question 22

Half life and time to peak theraputic effect of Liothyronine?

Answer 22

Circulating half life = 1day

Reaches peak levels in 2-4hr after oral administration

Question 23

How do you treat acute emergency hypothyroid conditions (like Myxedema Coma)?

Answer 23

IV formulation of Liothyronine

Question 24

[Levothyroxine/Liothyronine] is more potent by weight

Answer 24

T3 Liothyronine is 4x more potent on mcg for mcg basis

Question 25

``` Heart palpitations Nervousness Heat intolerance Excessive sweating Insomnia Tremors Frequent bowel movments Excessive weightloss Are all symptoms of what? ```

Answer 25

Thyroid hormone overdose -- similar to hyperthyroidism symptoms

Question 26

What is the most common preventable cause of mental handicap in the world?

Answer 26

Iodine deficiency --> goiter (hypothyroidism)

Question 27

What area is referred to as the "goiter belt"?

Answer 27

Great Lakes and Northwestern region of US

Question 28

What are 3 common causes of primary and secondary hypothyroidism?

Answer 28

Primary: Hashimoto's, Iodine Deficiency, Thyroid Ablation Secondary: Pituitary adenoma, pituitary surgery, radiotherapy

Question 29

What is the most common cause of hyperthyroidism and who does it most often affect?

Answer 29

Grave's disease -- autoimmune thyroid-stimulating antibodies activating thyrotropin receptor on thyroid cells Most often affect women 20-40 y/o

Question 30

What are the 4 common causes of hyperthyroidism?

Answer 30

1. Grave's disease 2. Nodular goiter --older age 90% of nodules are benign 3. Thyroiditis -- inflammation--> excess release 4. Thyroid cancer

Question 31

Mechanism of action of antithyroid drugs?

Answer 31

Inhibit Thyroid Peroxidase activity -- prevent organification of iodide and coupling of iodotyrosine

Question 32

Which antithyroid drug also reduces deiodination of T4 to T3 by inhibiting D1 deiodinase activity?

Answer 32

Propylthiouracil

Question 33

What are 3 severe side effects of antithyroid drugs (Methimazole, Propylthiouracil, Carbimazole)

Answer 33

1. Agranulocytosis (granulocyte less than 500/mm3) 2. Hepatitis 3. Lupus-like syndrome **These are absolute contraindications for further antithyroid drug therapy

Question 34

Propylthiouracil vs. Methimazole - -Longer half life - -Faster excretion - -Relatively less transplacental passage - -Higher Concentration in breast milk - -Higher Agranulocytosis risk

Answer 34

- -Longer half life = Methimazole - -Faster excretion = Propylthiouracil - -Relatively less transplacental passage = Propylthiouracil - -Higher Concentration in breast milk = Methimazole - -Higher Agranulocytosis risk = Propylthiouracil

Question 35

Mechanism of action of Radioactive Iodine?

Answer 35

131 I = thyroid specific Iodine isotope destroys sufficient thyroid tissue to restore euthyroid - -Emits beta particles and gamma rays - -5 day half-life

Question 36

Indications and contraindications for radioactive Iodine therapy?

Answer 36

Indication: relapsed hyperthyroidism after antithyroid drug therapy Contraindications: pregnancy, breast-feeding (passes to breast milk)

Question 37

Why are B-blockers used for hyperthyroid therapy?

Answer 37

Control symptoms -- tremor, anxiety, palpitations