Thyroid Flashcards
most active thyroid hormone
T3
Steps in Thyroid Hormone Synthesis
- TSH leads to stimulation of iodide (I-) uptake
- I- is oxidized to I2 by a peroxidase
- Tyrosines are then iodinated and bind to thyroglobulin
- Condensation then occurs:
Tyrosine + I = MIT (monoiodotyrosine)
MIT + I = DIT (diiodotyrosine)
MIT + DIT = T3
DIT + DIT = T4 - These condensates are still bound to thyroglobulin
- The hormones are released into plasma following proteolytic cleavage of the thyroglobulin
- Most circulating T3 and T4 are bound to thyroxine-binding globulin
Thyroid Hormones: MOA
- T3 and T4 must dissociate from thyroxine-binding proteins prior to entry into cells (diffusion or active transport)
- Inside the cell, T4 is deiodinated to T3
- T3 then enters nucleus and attaches to receptors
- Activation of these receptors promotes the function of RNA and subsequent protein synthesis
causes of hyperthyroidism
o Graves’ Disease: autoimmune Ab attack on TSH receptor ↓TSH
Ab stimulates ↑T3 & T4
o Tumor
o Thyroiditis
o Drug induced:
Ingest thyroid
Amiodarone (↓ conversion of T4->T3; contains iodide)
levels of TSH and T3/T4 in hyperthyroidism
T3/T4 is high
TSH is low
Hyperthyroidism (Thyrotoxicosis) Treatments:
- Surgery
- Radioactive iodine
- Antithyroid medications
Methimazole (Tapazole)
Propylthiouracil (PTU)
Methimazole (Tapazole)
MOA
- inhibits thyroid hormone synthesis
is Methimazole or PTU more potent?
Methimazole
- 10x as potent as PTU
does Methimazole or PTU have a faster onset and is longer acting?
Methimazole
FDA pregnancy category of Methimazole
D
what semester of pregnancy can Methimazole be taken
avoid in 1st trimester but favored agent in 2nd and 3rd
SE/ADEs of Methimazole
- dermatitis, myalgia, arthralgia, jaundice, edema, nephritis, agranulocytosis, hepatotoxic
o Serious side effects are due to agranulocytosis and hepatoxicity
o Also has issues with rashes (dermatitis)
what do you need to check before prescribing methimazole?
Need to check baseline CBC with differential and liver enzymes before treating
o To monitor for granulocytes and hepatotoxicity, get baseline liver enzymes to check for hepatotoxicity
o Need differential for liver enzymes
o If someone has liver damage or low count we wouldn’t use this medication
Propylthiouracil (PTU)
MOA
Inhibits thyroid hormone synthesis and prevents peripheral conversion
PTU prevents periheral conversion of T4 to active T3
BBW for PTU
- BBW: hepatotoxicity (including fatal) so is mainly used if methimazole fails
does Methimazole or PTU have higher risk of causing liver damage?
Propylthiouracil (PTU)
three reasons to use PTU over methimazole
1st trimester of pregnancy if they fail methimazole, and people who have more severe thyroid storm
mainly first trimester of pregnancy
PTU should be taken during which trimester of pregnancy?
favored during 1st trimester
SE/ADEs of Propylthiouracil (PTU)
o Derm, GI, arthritis, vasculitis
o Granulocytopenia, leukopenia
why does PTU and methimazole onset of action take so lone?
- There is a delay in action of these drugs
- This delay is due to MOA and the fact that there will still be circulating thyroid hormone
- These drugs will not work quickly for symptoms
- can be problem for cardiac arrhythmia symptoms
- These drugs only affect syntheses mainly- circulating thyroid hormone has to deplete which can take weeks
Advantages of Methimazole
- More rapid achievement of euthyroidism (few weeks)
- Once-daily dosing and better compliance
- Little or no effect on subsequent success of radioiodine therapy (unlike PTU, which is associated with an increase in radioiodine failure rates)
- Less toxicity
When You Might Choose PTU
- In pregnant women during their first trimester
- In patients with life-threatening thyrotoxicosis or thyroid storm (because of PTU’s ability to inhibit peripheral conversion of T4 to T3)
- In patients with adverse reactions to methimazole (other than agranulocytosis) who are not candidates for radioiodine or surgery
- Pharmacologic dose of iodide inhibits the iodination of ___.
tyrosines
- Iodide is not used much now except in ______ (it decreases thyroid vascularity)
thyroid storm or prior to surgery
