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34 Cards in this Set
- Front
- Back
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List (in general) the 5 major steps of TH synthesis.
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(1) Iodide uptake into follicular cells
(2) Oxidation of iodide (3) Coupling (4) Storage (5) Proteolysis and release |
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Describe the uptake and oxidation of iodide in the process of TH synthesis.
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TSH is released by the ant. pituitary, which stimulates the activity of an active I-transport pump on the follicular cell membrane.
Iodide is pumped in, and, in the presence of thyroidal peroxidase and H2O2, is oxidized and incorporated into thyroglobulin. |
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Describe the coupling, storage and proteolysis steps in TH synthesis.
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Once iodide is oxidized and incorporated into thyroglobulin, structural changes occur.
In the presence of thyroidal peroxidase and H2O2, two DIT molecules or one DIT and one MIT molecules are coupled to form T3 and T4. Thyroglobulin (with DIT, MIT, T3 and T4) moves from the follicular cells to the colloid and is stored there. Upon secretory stimuli, thyroglobulin is resorbed back into the follicular cells via endocytosis. A phagolysosome is formed, thyroglobulin is lysed and DIT, MIT, T3 and T4 are liberated. MIT and DIT are deiodinated and the iodide is reused to synthesize more TH. Liberated T3 and T4 are secreted into circulation. |
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Starting with iodide uptake by follicular cells as the 1st step, place the following TH synthesis/release steps in order..
(a) DIT + DIT coupled in the presence of TPO and H2O2 (b) thyroglobulin moves from colloid to follicular cell (c) iodide is oxidized by thyroid peroxidase into thyroglobulin (d) thyroglobulin moves from follicular cell to colloid (e) thyroglobulin lysed in the follicular cells (f) liberated T3, T4 released into the circulation (g) TSH secretory stimulus |
Starting with iodide uptake by follicular cells as the 1st step...
1 - (c) iodide is oxidized by thyroid peroxidase into thyroglobulin 2 - (a) DIT + DIT coupled in the presence of TPO and H2O2 3 - (d) thyroglobulin moves from follicular cell to colloid 4 - (g) TSH secretory stimulus 5 - (b) thyroglobulin moves from colloid to follicular cell 6 - (e) thyroglobulin lysed in the follicular cells 7 - (f) liberated T3, T4 released into the circulation |
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Do the following proteins bind T3, T4 or both?
(1) albumin (2) TBPA (3) TBG |
(1) albumin: both
(2) TBPA: T4 (3) TBG: both |
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Compare T3 and T4 based the following parameters..
(1) protein binding (2) half life (3) vol of distribution (4) potency (5) origin |
Compare T3 and T4 based the following parameters..
(1) protein binding : T4 is mostly protein bound (2) half life : T4 has longer half-life; T3 is more rapid acting (3) vol of distribution: T3 has higher Vd (35L) (4) potency: T3 is 3-4x more potent than T4 (5) origin: 100% of T4 is from thyroid vs. 20% of T3; rest of T3 is from peripheral conversion |
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Name the 5 agents that inhibit 5'-deiodinase.
How would these affect T4 levels? T3 levels? |
Agents that inhibit 5'-deiodinase:
(1) PTU (2) iopanoic acid (3) amiodarone (4) propanolol (5) glucocorticoids These agents would decrease T3 because they would inhibit the conversion of T4 to T3 in the folicular cells. |
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List 4 potential causes of primary hypothyroidism.
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Causes of primary hypothyroidism..
(1) congenital defect (2) iodine deficiency (3) Hashimoto's (4) postablative |
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Which of the following statements is true:
(a) Serum TSH levels would be markedly high in secondary hypothyroidism (b) T3 levels are always low in hypothyroidism (c) TSH levels would be low in primary hypothyroidism (d) There is a low response to TRH in the case of secondary hypothyroidism |
True statement:
(d) There is a low response to TRH in the case of secondary hypothyroidism Other answers: (a) Serum TSH levels would be low (not high) in secondary hypothyroidism (b) T3 levels can be low or normal in hypothyroidism while T4 is low in all hypothyroid conditions (c) TSH levels would be high in primary hypothyroidism |
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What are the 2 general treatments for hypothyroidism?
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(1) iodide supplementation
(2) replacement therapy |
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What is endemic goiter?
How do you treat endemic goiter? |
Endemic goiter results when a person does not have sufficient iodide in his diet. (the thyroid works fine, it just doesn't have any iodide to make TH).
To treat endemic goiter, iodide is usually given with T4. This will produce a negative feedback effect on TSH secretion, which prevents an acute hyperthyroid event. |
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Normally, the thyroid secretes about 80ug of T4 per day.
Why, then, would a hypothyroid patient need to take a full replacement dose of T4 between 150-200 ug/day? |
The difference is due to absorption pharmacokinetics. Between 50-75% of replacement TH therapy is actually absorbed due to 1st pass metabolism.
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TH replacement therapy is used to treat hypothyroidism.
What are the 2 options for replacement therapy? Which option is preferred? |
(1) organic TH extracts
(2) synthetic TH preparations (preferred) |
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What are the 3 options for synthetic TH replacement therapy in treating hypothyroidism?
For the 3 drugs, which is an isomer of T4? of T3? mixture? |
(1) levothyroxine: T4 isomer
(2) liothyronine: T3 isomer (3) liotrix = mixture of T4 and T3, 4:1 ratio |
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What are the advantages of levothyroxine compared to liothyronine and liotrix?
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Levothyroxine is an isomer of T4. It provides a large pool of T4 that can be converted to T3.
Since T4 has a longer half-life vs. T3, it is not as serious when a pt misses a dose of levothyroxine. Lastly, T3 profiles are more uniform with levothyroxine administration compared to T3 administration. |
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In a patient with a goiter + increased TSH, low T4 + normal T3, what is the benefit of giving her exogenous TH?
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Exogenous TH will suppress TSH secretion so that the thyroid will return to normal size with deficient output of T4.
Normal TH levels, however, will be maintained by the exogenous TH being administered. |
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List the 3 causes of primary hyperthyroidism.
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(1) Graves Disease
(2) trophoblastic tumor (3) chronic thyroiditis |
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Describe the pathogenesis of Graves Disease.
What symptoms would a patient with Graves have? |
Graves results from autoantibodies produced to TSH receptors. These autoAb's stimulate cells to overproduce T3 and T4.
Symptoms include: --thryoid enlargement --heat intolerance --dec in weight, inc in appetite --ocular changes --hand tremors |
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What are the 6 primary options for treating hyperthyroidism?
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(1) thioamides
(2) monovalent anion inhibitors (3) pharmacologic doses of iodide (4) iodinated contrast media (5) radioactive iodide (I-131) (6) Adrenoreceptor-blocking agents |
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What are the 2 main thioamides used to treat hyperthyroidism?
What is their primary mechanism of action? |
(1) propylthiouracil (PTU)
(2) methimazole They inhibit the organification and coupling steps in TH synthesis via inhibition of thyroid peroxidase. In addition, PTU inhibits peripheral 5'deiodinase. |
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Regarding thioamides..
(1) Describe their vol of distribution. (2) Describe their half-lives. (3) Describe their onset of effect. (4) What can happen if you prescribe too large of a dose? (5) How often do patients taking thioamides relapse? |
Regarding thioamides..
(1) have high volumes of distribution (2) have short half-lives (3) take a long time for onset of effect because the TH storage pool must be depleted (4) Excessive dosing can lead to secondary hypothyroidism (5) 60% of pts on long-term thioamide treatment relapse |
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What are the adverse effects of PTU and methimazole?
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--maculopapular pruritic rash
--lupus-like syndrome --agranulocytosis |
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List the 3 monovalent anion inhibitors used to treat hyperthyroidism.
What is their primary mechanism of action? |
(1) perchlorate
(2) pertechnetate (3) thiocyanate These drugs competitively block iodide uptake by follicle cells. |
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What drug could you administer to a patient with amiodarone-induced hyperthyroidism?
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Perchlorate (monovalent anion inhibitor)
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List the 3 main beneficial effects of giving pharmacological doses of iodide as treatment for hyperthyroidism.
Which effect is the most important therapeutic effect? |
(1) transiently inhibits organification of iodide
(2) dec release of T3, T4 (most important) (3) reduces vascularity of hyperfunctioning thyroid |
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Describe the 3 indications for administering pharmacologic doses of iodide.
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(1) acute thyroid crisis
(2) severe thyrocardiac disease (3) surgical emergencies |
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At what "level" do pharmacologic iodide doses act to decrease the release of T3 and T4?
(a) coupling (b) storage (c) proteolysis |
At what "level" do pharmacologic iodide doses act to decrease the release of T3 and T4?
(c) proteolysis |
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List some adverse effects of pharmacological dosing of iodide.
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--acneiform rash
--drug fever --metallic taste --bleeding disorder These adverse effects are uncommon and usually reversible with cessation. |
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What is the main indication for iodinated contrast media?
What is its off-label use? What is its mechanism of action? |
Main indication: diagnosis of thyroid disease
Off-label use: adjuvant therapy in thyroid storm Mechanism of action: inhibition of peripheral deiodination and the suppression of T3, T4 production |
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Describe the mechanism of action of radioactive iodide.
What are its major drawbacks? |
I-131 is an isotope of iodine and, just like iodine, accumulates in the thyroid, is used in TH synthesis and stored in the colloid.
I-131 emits beta particles which penetrate only a small distance in the tissue and destroy some surrounding follicular tissue. This results in decreased TH synthesis. Drawbacks include: --post-radiation hypothyroidism --replacement therapy must usually follow --crosses placenta and excreted in breast milk |
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Why are beta-blockers helpful in treating hyperthyroidism?
What is the drug of choice? |
Hyperthyroid effects are similar to SNS stimulation so beta-blockers can prevent many of the symptoms of thyrotoxicosis.
Propanolol is the drug of choice. It can treat HTN, tachycardia and atrial fibrillation that may occur with thyrotoxicosis. |
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What is a thyroid storm?
What agents are used to treat symptoms and prevent thyroid release? |
A thyroid storm is a life threatening episode of severe acute thyrotoxicosis.
Agents used to treat symptoms and prevent TH release include: --propanolol --iodine (saturated) --PTU Other treatments: --anti-pyretics --treat HF that may occur as a result of the thyroid storm --treat underlying infection that may be the cause of the storm |
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Besides measuring serum TH, TSH and TRH levels for the diagnosis of hypothyroidism, what other indices can be used to determine if a patient is hypothyroid?
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Other indices to diagnose hypothyroidism:
(1) I-123 uptake is low (2) elevated serum cholesterol (3) elevated CPK and ALT (4) pernicious anemia |
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Predict the relative T3, T4 and TSH levels, as well as the TRH response (high, low, normal) for the following:
(1) primary hypothyroidism (2) secondary hypothyroidism (3) tertiary hypothyroidism |
T4 will be low in all conditions
(1) primary: normal or low T3, high TSH, high TRH response (2) secondary: normal or low T3, low TSH, low TRH response (3) tertiary: normal or low T3, possibly normal TSH, delayed TRH response and levels are variable |
