Term
| what is actively taken up in the thyroid for biosynthesis of thyroid hormones? |
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Definition
| iodide - active process; concentrated in the gland |
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Term
| what is the fate of iodide in the thyroid gland? |
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Definition
| incorporation into thyroglobulin by thyroidal peroxidase |
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Term
| what happens upon stimulation of the thyroid gland by TSH? |
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Definition
| proteolysis of thyroglobulin and the release of thyroxine (T4) and triiodothyronine (T3) into the blood |
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Term
| what is needed for the release of T3 and T4 into the blood? |
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Definition
| stimulation of the thyroid gland by TSH and proteolysis of thyroglobulin |
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Term
| what is the state of T3 and T4 in the blood? |
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Definition
| 99% bound by plasma protein |
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Term
| 60% of circulating T3 comes from where? |
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Definition
| the deiodination of T4 by the peripheral tissues |
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Term
| which is more potent T3 or T4? |
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Definition
| T3 is about 5x more potent than T4 |
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Term
| where is the enzyme located that converts T4 to T3? |
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Definition
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Term
| elimination of T4 and T3? |
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Definition
conjugated with glucuronic and sulfuric acid and excreted in the bile
majority is actually recycled |
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Term
| what enzyme is responsible for generating 60% of circulating T3? |
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Definition
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Term
| where is 5'-deiodinase-I located? |
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Definition
|
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Term
| what is the role of 5'-deiodinase-I? |
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Definition
| converts T4 to T3 in the periphery |
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Term
| is 5'-deiodinase-I regulated? |
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Definition
YES
can be inhibited by drugs |
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Term
| regulating 5'-deiodinase-I is one way to do what? |
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Definition
| regulate the amount of circulating hormones |
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Term
| T3 is _____ times more potent than T4 |
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Definition
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Term
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Definition
|
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Term
| how is thyroid hormone synthesis and secretion regulated? |
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Definition
positive regulation - TSH
negative regulation - somatostatin
both from the hypothalamus |
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Term
| where does TSH work in hormone secretion and biosynthesis? |
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Definition
|
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Term
| release pattern of thryoid hormones during the day? |
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Definition
| relatively constant release pattern |
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Term
| thyroid hormones play an important role in in the body? |
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Definition
| development, growth, increase oxygen consumption, and protein synthesis |
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Term
| what accounts for most of the biological activity of thyroid hormones? |
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Definition
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Term
| how do thyroid hormones act on the target cells? |
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Definition
| through intracellular receptors that are transcription factors |
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Term
| what makes up the functional receptor unit to activate thyroid-responsive genes in a target cell? |
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Definition
| a heterodimer of thyroid hormone receptor and retinoid X receptor |
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Term
| what is the classic assay for thyroid hormones effect? |
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Definition
| an increase in oxygen consumption and protein synthesis |
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Term
| are thyroid hormones bound by binding proteins in circulation? |
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Definition
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Term
| onset and offset of thyroid hormones? |
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Definition
| slow because they cross the membrane and bind to receptors in the nucleus as transcription factors |
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Term
| causes of hypothyroidism? |
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Definition
1. hashimoto's thyroiditis - autoimmune
2. radiation
3. congenital
4. iodine deficiency
5. drug induced |
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Term
| what are some drugs that can cause hypothyroidism? |
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Definition
1. octreotide - decreases TSH secretion
2. amiodarone - contains a lot of iodide which inhibits thyroid hormone release
3. lithium - does the same as 2
4. resins for high cholesterol - binds thyroxine in the GI tract
5. glucocorticoids, B antagonists - inhibits synthesis of T3 in the tissue |
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Term
| what is the gold standard treatment for hypothyroidism? |
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Definition
| levothyroxine - synthetic thyroxine |
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Term
| levothyroxine is inherently what? |
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Definition
| inherently unstable - affected by heat and light |
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Term
| what is the major concern with levothyroxine? |
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Definition
| the development of cardiac dysrhythmias |
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Term
| why is the development of arrhythmia a problem with levothyroxine use? |
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Definition
because B adrenergic responsiveness is a thyroid dependent phenomenon
hypothyroid - have increased HR, tremor, and sweating
increased HR, contractility, and myocardial oxygen demand --> may lead to arrhythmia |
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Term
A 45-year-old female is taken l-thyroxine following her thyroidectomy. Her physician tells her to take the medications at a different time of day than one of her other medications. The most likely reason for this is:
a. L-thyroxine is only loosely bound by plasma proteins – highly
b. The intestinal absorption of l-thyroxine can be quite variable and is affected by certain medications
c. L-thyroxine has a short half-life in the plasma – highly bound; long half life
d. Some medications can increase the renal excretion of l-thyroxine |
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Definition
| b. The intestinal absorption of l-thyroxine can be quite variable and is affected by certain medications |
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Term
| 5 ways to treat hyperthyroidism? |
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Definition
1. ionic compounds - not used as drugs
2. iodine containing compounds
3. radioactive iodide - iodide 131
4. thionamides
5. B adrenergic antagonists |
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Term
| how do ionic compounds work to treat hyperthyroidism? |
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Definition
|
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Term
| examples of ionic compounds used in hyperthyroidism? |
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Definition
|
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Term
| what is lugol's solution? |
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Definition
an iodine containing compound used to treat hyperthyroidism
contains 5% iodine, 10% potassium iodide |
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Term
| what is an iodine containing compound used to treat hyperthyroidism? |
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Definition
|
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Term
| how does lugol's solution work to treat hyperthyroidism? |
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Definition
| inhibits release of T3 and T4 |
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Term
| when is lugol's solution effective in treating hyperthyroidism? |
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Definition
| in the short term with excess thyroid hormone secretion |
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Term
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Definition
1. prior to thyroidectomy surgery
2. to compete with radioactive iodide in the event of a nuclear reaction - blocks uptake of ALL iodide |
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Term
| why can lugol's solution be used in the even of a nuclear reaction? |
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Definition
| it blocks the uptake of ALL iodide |
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Term
| why is lugol's solution not effective long term? |
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Definition
| the gland escapes after several weeks from the effect of iodine |
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Term
| use of radioactive iodide? |
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Definition
| to destroy the thyroid gland by beta radiation |
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Term
| benefits of radioactive iodide in the treatment of hyperthyroidism? |
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Definition
given as a single does; safe; low cost
standardization is difficult |
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Term
| when is radioactive iodide contraindicated and why? |
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Definition
absolutely contraindicated in pregnancy
crosses the placenta and is concentrated in the fetal thyroid gland and destroys it as well |
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Term
| side effect of radioactive iodide as a treatment for hyperthyroidism? |
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Definition
consequent hypothyroidism
80% get some level and 20% will require treatment for it |
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Term
| why is radioactive iodide only used in people over 35? |
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Definition
| there is a concern for developing cancer later in life so it is only used when a person is older and likely to have something else kill them before that happens |
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Term
| 2 thionamides used to treat hyperthyroidism? |
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Definition
1. propythiouracil (PTU)
2. methimazole |
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Term
| mechanism of action of thionamides? |
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Definition
both inhibit thyroid biosynthesis by inhibiting thyroid peroxidase
PTU also inhibits 5'-deiodinase-I which reduces the production of T3 in the peripheral tissue |
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Term
| how does the mechanism of action of PTU differ from methimazole? |
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Definition
PTU also inhibits 5'-deiodinase-I (along with thyroid peroxidase)
this reduces the production of T3 in the peripheral tissues |
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Term
| benefit of treating hyperthyroidism with thionamides? |
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Definition
they can suppress autoimmunity and reduce the titer of circulating thyroid Abs
the patient can go off medications |
|
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Term
| side effects of thionamides? |
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Definition
1. rash, arthralgia, fever (2-5%), agranulocytosis (0.2%)
2. PTU has low transplacental passage and breast milk distribution
3. methimazole has been rarely associated with congenital abnormalities |
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Term
| what is a severe side effect of PTU? |
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Definition
hepatic toxicity/failure
3rd leading cause of liver transplant due to drug toxicity |
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Term
| methimazole is less toxic than PTU but can cause what side effect? |
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Definition
| cholestatic jaundice - which is reversible |
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Term
| what are the 2 times to use PTU over methimazole? |
|
Definition
1. life-threatening thyroid storm because of it's 5'-deiodinase inhibition
2. during pregnancy |
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Term
| how are B adrenergic antagonists used in the treatment of hyperthyroidism? |
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Definition
| they reduce the activity of thyroid hormones on target tissues |
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Term
| what B antagonist is used to treat hyperthyroidism? |
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Definition
|
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Term
| when are B antagonists used to treat hyperthyroidism? |
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Definition
| when there is an immediate need to block the effects of thyroid hormones |
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Term
| why are B antagonists effective against hyperthyroidism? |
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Definition
the effects of thyroid hormones mimic excess sympathetic activity - tachycardia, dysrhythmias, sweating tremors
these symptoms can be alleviated by blocking B-adrenergic receptors until the gland is depleted of thyroid hormone |
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|
Term
| why are most drugs to treat hyperthyroidism not immediate? |
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Definition
| the thyroid gland stores about 3-4 weeks of thyroid hormone so drugs aren't effective until this store has been depleted |
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