Thyroid Pharm-IL- Thyroid-Leah :)

Question 1

How is IODINE taken up into follicular cells for thyroid hormone synthesis?
Thyroid:plasma ratio of iodine?

Answer 1

• Active absorption via Na/I symporter (requires ATP)
• Normal is 20-50:1
• Thyroid can concentrate iodine up to 100x more than plasma!

Question 2

What inhibits follicular iodine uptake? (2)

stimulates? (1)

Answer 2

• uncouplers of ox phos (thiocyanate, perchlorate) inhibit uptake
• TSH stimulates

Question 3

Describe the process of organification:

Answer 3

Step 1: oxidation of iodide via thyroid peroxidase + H2O2

Step 2: thyroglobulin is iodized at tyrosyl residues to form MIT/DIT (basically T1/T2 if such a thing existed)

Question 4

How are T3/4 formed?

Where are these hormones formed?

Answer 4

• MIT + DIT –> T3
• DIT x 2 –> T4
• Catalyzed by thyroid peroxidase + H2O2 like organification
• stored in the center of follicles as “colloid”

Question 5

How is thyroid hormone released from thyroid to blood?

Answer 5

• Endocytosis is stimulated by TSH
• Thyroglobulin taken up into lysosomes and broken down
• T3/4 sent to blood, MIT/DIT recycled for iodine

Question 6

What inhibits thyroid hormone release? (2)

Answer 6

• iodine (inversely modulates secretion)

- lithium

Question 7

What are the carriers of T3/4 in plasma? (2)

Answer 7

• Thyroxine Binding Globulin (TBG) carries both T3/4

- Transthyretin carries T4

Question 8

Which thyroid hormone has the highest concentration in blood? Which is more active?

** IMPORTANT CARD!!!**

Answer 8

• T4 HAS HIGHEST PLASMA CONCENTRATION.

- T3 IS MORE ACTIVE

Question 9

What enzyme converts T4 to T3?
What are the two important isoenzymes of this enzyme?
Which is responsible for MOST of the conversions?
Which is responsive to propylthiouracil?

Answer 9

iodothyronine 5′-deiodinase

D1: liver, kidney, thyroid – responsible for MOST conversion; INHIBITED by propylthiouracil
D2: brain, pituitary, cardiac/skeletal muscle

Question 10

In what organ is the deiodinase enzyme most active?

How can this be increased even more than usual?

Answer 10

• Liver

- ^^ by CYP450 INDUCERS

Question 11

Primary Hypothyroid lab findings:
Most common cause:
Two other causes?

Answer 11

• HIGH TSH, LOW T3, T4
• Autoimmune/ Hashimotos most common
• thyroid damage via Iodine radation/ surgical removal

Question 12

Hormone findings and cause of SECONDARY hypothyroid?

Answer 12

-TSH LOW (pituitary lesion, loss of TRH from hypothalamus) –> T3, T4 LOW

Question 13

Drug of choice for thyroid hormone supplementation?
Why?
How long does it take to reach steady state?

Answer 13

• levothyroxine (T4)
• consistent, long acting, once daily dosing
• t 1/2 = 6-7 days–> can take up to a MONTH to reach steady state.

Question 14

What is liothyronine and when might it be used?

Why isn’t it the drug of choice for primary hypothyroid?

Answer 14

• T3, not used in primary hypothyroid but might be used in deiodinase deficiency
• variable response, short t1/2

Question 15

In addition to INCREASING T4 levels, what can levothyroxine be used to do?
List 2 additional therapeutic uses.

Answer 15

DECREASE TSH via negative feedback–>

Treats thyroid carcinomas, goiters

Question 16

When might levothyroxine be given IV?

Answer 16

• myxedema coma

- (severe hypothyroid)

Question 17

What are four agents that may reduce levothyroxine bioavailability?

Answer 17

• cholestyramine, colesevelam (bile sequestrants)
• calcium carbonate
• aluminum hydroxide

Question 18

How does estrogen effect levothyroxine?

Glucocorticoids?

Answer 18

• Estrogen INCREASES thyroid binding globulin (TBG)–> INCREASE levothyroxine doses if given with OCPs
• Glucocorticoids DECREASE TBG–> DECREASE levothyroxine doses

Question 19

In addition to propylthiouracil, what drug inhibits deiodinase?

Answer 19

amiodarone

Question 20

How does thyroxine effect warfarin?

Answer 20

• Thyroxine INCREASES anticoagulant activity–> DECREASE warfarin dose
• ^^ catabolism vitamin K dep. factors

Question 21

Effects of levothyroxine on the cardiovascular system (3)?

Answer 21

-tachycardia
-palpitations
-HTN
(Sympathetic effects, just like T4)

Question 22

Most common form of HYPERthyroidism?
Describe the pathogens is of this disorder.
What are the assc hormonal findings?

Answer 22

• Graves
• Ab’s bind TSHR/ Follicular cells to ^^ thyroid hormone production
• ^^ T3/T4, low TSH

Question 23

Five treatments for HYPERthyroid?

Answer 23

• propanolol (cardio sx)
• NSAIDs (inflammatory sx)
• propylthiouracil (antithyroid)
• methimazole (antithyroid)
• radioablation therapy

Question 24

Propylthiouracill and methimazole MOA (2):

Which has a longer t1/2 and is the DOC?
Which is the DOC in pregnancy?

Answer 24

• block organification (both)
• block MIT/DIT –> T3/4 (both)
• PROPYLTHIOURACIL ONLY blocks peripheral deiodinase (T4 –> T3)
• Methimazole has 6 hr t1/2 and is DOC
• Propylthiouracil is DOC in preggos

Question 25

Methimazole:

3 most serious ADRs

Answer 25

Agranulocytosis + Aplastic anemia + Abnormal babies

Methim(A)zole causes (A)plastic (A)nemia + (A)granulocytosis + (A)bnormal babies!!

Question 26

Propylthiouracil two most serious ADRs?

Answer 26

-hepatic necrosis, nephritis

LIVER INJURY IS BLACK BOX WARNING

Question 27

When do you use Iodine-131 (3)?

What can it induce?

Answer 27

This is radioactive iodine, destroys thyroid tissue
Want to use in hyperthyroid, graves, carcinoma of thyroid.

-Induces hypothyroid (goal), but may decrease function TOO much

Question 28

When is radioablation therapy contraindicated?

Answer 28

pregnancy!! radioactive iodine crosses placenta

Question 29

In nuclear power plant accidents, how is the uptake of radio-iodine prevented?

Answer 29

supplementation with excess iodine