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106 Cards in this Set
- Front
- Back
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what is important to understand about how long it will take for drugs lowering thyroid hormone levels to work?
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it will take weeks bc thyroid hormone is made and stored in large quantities in the follicles.
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what is the function of the thryoid?
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secretion of thyroid hormones and calcitonin
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what are the major roles of thyroid hormone/
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growth
develpment body temp reg metabolic rates of cells aides in these pathways doesn't directly cause temp regulation is done by epinephrine from sympathetic system but it epinephrine wont cause the temperature regulation in the absence of thyroid hormone. |
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what does epinephrine need in order to stimulate body temperature change?
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thyroid hormone.
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what is the pathway for thyroid hormone release?
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hypothalamus relsease TRH
stimulates release of TSH from anteriorpituitary. Which in turn stimulates synthesis and release of T3 and T4 from the thyroid gland. |
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what are the controls of TRH and TSH release?
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stress - inhibits
heath- inhibits cold- stimulate -fasting- inhibits overfeeiding-stimulates increased iodine- inhibits decreased iodine - stimulates High levels of T3/4 - inhibits low levels of T3/4- stimulates |
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what is the difference btw T4 and T3 structurally?
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T3- has 3 Iodines
T4- has 4 |
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what are the 5 major steps of thyoid hormone synthesis?
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1.uptake of Iodine
2. oxidatino/activation of idodine 3. coupling into Tg 4. storage 5. proeolysis and release. |
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what is the the cell to plasma ratio of Iodine in folicular cells and how is that maintianed?
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40:1
Iodine pump in follicular cell membrane which is stimulated by TSH |
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what is the enzyme responsible for oxidizing and incorporating Iodion into thyroglobulin(Tg)?
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thyroidal peroxidase(TPO)
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what are the two molecules produced by thryglobulin(Tg) attack of tyrosine? in the second step of T3/4 synthesis?
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MIT and DIT
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what is the couplings that occur to create T3 as opposed to T4?
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MIT couples with DIT to create T3
two DITs couple to create T4 MIT never couples with itself. |
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what catalyzes coupling reaction in T3/4 synthesis?
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TPO
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what are the two ways T3 is produced IN THYROID GLAND?
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MIT coupling with DIT creates T3
after proteolysis and release from storage and prior to release into the blood some T4 will be deiodinated into T3 by 5`deiodinase. |
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what is important about 5'deiodinase activity that takes place in the thyroid gland as oppposed to the periphery?
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This 5'deiodinase is not targetable by PTU.
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what are the differences btw T3 and T4? in relation to acitivty and orgin?
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T3 is hormonally active but T4 is probably just a prohormone that is converted into T3.
T4 comes exclusively fromt eh thryoid gland T3 also comes from peripheral deiodination of T4 Treating anathyroidal individuals with T4 will give near normal levels of T3 |
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what is the difference in distribution of T4 as opposed to T3?
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T4 is limited to plasma while T3 can distribute to entire body water.
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what are the half lifes of T3 and T4?
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T3- 1-2 days
T4- 6-7 days |
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what are the two indirect mechanisms of modulating T3/4 activity
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affecting binding proteins
inhibiting 5'deiodinatino of iodothryonines |
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what are the T3/4 binding protiens/
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TBG-thyroxine binding globulin, binds t3 and 4
TBPA- thyroxine binding prealbumin binds T4 only albumin- binds just about everything including T3 and T4. |
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what is the effect of decreased levels of TBG?
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relative hyperthyroidism bc there will be an increase in the amount of free T3/4.
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what is the effect of Propylthiouracil(PTU)?
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inhibits peripheral 5'deiodinase
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What is the effect of propranolol on thyroid hormone?
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inhibits 5'deiodination
secondary benifit when used to treat thyroid storm. primary use is to treat the hypertension and tachycardia. |
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what are the drugs that can inhibit 5'deiodinase?
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Propylthiouracil(PTU)
iodinated contrast media(iopanioc acid) Amiodarone(antiarrhythmic agent) propranolol pharmacologic doses of glucocorticoids |
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what is myxedema?
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hypothyroidism
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what are the causes of myxedema?
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congential defect of thyroid
iodine deficiency chronic autoimmune(hashimotos) thyroiditis postablative panhypopitutarism(secondary hypothyroidism) hypothalmic problems(tertiary hypothyroidism) |
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what are neonatal symtoms of hypothyroidism?
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cretinism
usually presents firist month after birth manifests as jaundice, constipation, somnolence, and feeding problems this can be hard to differentiate from normal behavior and since this can lead to major developmental concerns all infants are screened for T4 and or TSH levels |
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what are the young child symptoms of hypothyriodism?
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protruding tongue
broad flat nose, wide set eyes dry skin, coarse hair imparied mental development retarded bone growth/dentition enlarged gland |
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what is the presentation of hypothyroidism in older children?
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retardation of linear growth
delayed puberty poor school performance |
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what are the manifestation of hypothyroidism in adults?
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fatigue, lethargy, constipation
slowing of the central and muscular activity decreased appetite, increased weight deeper, hoarse voice severe myxedema-doughy cool skin, enlarged heart, can lead to coma |
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what are expected T4 and freeT4 values seen in differnt hypothyroid conditions?
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T4 and FT4I are low in all conditions that induce hypothyroidism.
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what is T3 and FT3I levels in hypothyroid conditions?
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in most cases it will be low, but it can be normal if T4 deiodination is able to compensate in this case T4 will be low and T3 will be normal pt still considered hypothyroidic even though they will be asymptomatic.
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what is serum TSH levels in the different forms of hypothyroidism?
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TSH is high in primary hypothyroidism and usually results in a goiter
TSH will be normal or low in secondary or tertiary hypothyroidism. |
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What is TRH response?
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TRH response is a test which measures TSH levels in response to TRH.
in primary hypothyroid TSH levels will be high in response to a dose of TRH in secondary TSH levels will be low and flat even in response to TRH in tertiary TSH levels will go up but only after a delayed response and will be low prior to dose. this is bc it takes some time for the pituitary to react to sudden TRH after going so long without it. |
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what are some of the indicators and lab values important in measuring and assessing hypothyroidism?
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T4,FT4I
T3, FT3I TSH 123I uptake- low in hypothyroidisms elevated serum cholesterol(primary hypothyroidism) elevated CPK and ALT Pernicious anemia(autoimmune mediated hypothyroidism hashimotos) |
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what are the treatments for hypothyroidism?
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iodide supplementation
thyroid hormone suppliementation |
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what is the epidemiology of iodide defiency ?
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rarely seen in US since 1920 due to iodide added into salt.
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what is Iodide supplementation used to treat?
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endemic goiter
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what is complicated about treating endemic goiter?
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problem is not in the gland. its a defiency of iodine.
gland is enlarged so if you provide iodine you will actually cause massive surge in production which will cause hyperthyroidism. |
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how do you prevent hyperthyroidism in treatment of endemic goiter?
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suppliment for a time with thyroid hormone to decrease enlargment then suppliment Iodine.
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what are some concerns with administration of replacement thyroid hormone?
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patients are quite sensitive to exogenous thyroid hormone due to decreased metabolic acitivy especially the elderly and those with CHF so full replacement dose is not given immediatedly but titrated up to.
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what is the replacement dose of thyroid homrone?
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thryoid secretes 80ug of T4/day
full replacement dose is 150-200ug/day in a 70kg male bc only 50-75% oral absorption. must monitor regularly to ensure that dose is both adequet and not reaching toxic levels bc amount of replacement needed is directly related to severeity of deficit. |
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what is the pathology behind normal T3/4 with goiter?
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enlarged thyroid is needed to meet demands due to problem treat this with supplimentation of TH to maintian normal levels and take stress off gland so it can shrink back to normal.
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What are the organic TH extracts?
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thyroid USP
Thyroglobulin USP |
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what are the advantages and disadvantages of organic TH use?
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they are cheaper but have major variability and safetly issues mainly with immune responses
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what type of TH is prefered for treatment?
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synthetics
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what is thyroid USP?
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desiccated powder from animal thyroid glands
contains .17 to .23% of organic iodide bc of variabliliity in batches comercially available products are not bioassayed so potency is not know. availabe in tablets containing 15-500mg of the powder |
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what is Thyroglobulin USP?
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purified extract of pig thyroid
contains USP standard iodide content it is bioassayed( potency is known) available 15-300mg tablets. |
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what is the drug of choice for TH replacement?
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levothyroxine
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what is levothyroxine?
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L isomer of synthetic T4
sodium salt |
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what is the dosages available for levothyroxine?
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25-5--ug
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what are the advantages of levothyroxine?
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more uniform preparation when compared to thyroid USP
provides large pool of T4 that can be converted to T3 missing a dose is not as serous as compared to supplementing T3 T3 serum profiles more uniform than with T3 administration(bc the body decided when to convert this to T3 and when to just keep it as T4) |
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what is the problem with Levothyroxine?
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its not effective in people who can't convert T4 to T3 such as people with liver disease
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Why is it hard for people with severe liver disease to convert T4 to T3?
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because liver is main site of peripheral 5'deiodoninase.
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what is liothyronine?
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L isomer of synthetic T3
sodium salt |
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what is dosing for Liothyronine?
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5-50ug
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what is Liotrix?
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mixture of levothyroxine and liothryonine
4:1 mix developed to mimic normal thryoid releases. |
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what is thyrotoxicosis?
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hyperthyroidism
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what are the causes of hyperthyroidism?
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graves disease
trophoblastic tumor chronic thryoiditis pituitary tumor(secondary) nigestion of contaminated foods. |
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what is the most common cause of hyperthyroidism?
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graves disease.
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what is graves disease pathology?
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autaoantibodies to receptors for TSH stimulate cells to overproduce T3/4
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who is graves disease most common in?
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older women
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what are the symptoms of graves disease?
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thyroid enlargment
heat intolerance decreased weight, increased in appetite, diarrhea, tiredness, irritablility, heart problems, ocular changes, hand tremors. |
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what is the eye problem in graves disease?
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eyes bug out due to muslce behind eyes that has receptors for T3/4
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what are the drug therapies for hyperthyroidism?
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thiourea derivatives(thioamides)
monovalent anion inhibitors High dose iodides iodinated contrast media radioactive iodide adrenoreceptor antagonists |
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what are the thioamides?
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propylthiouracil
(PTU) methaimazole |
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what are the monovalent anion inhibitors
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potassium perchlorate
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what are the iodinated contrast media?
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ipodate
iopanoic acid |
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what are the adrenorecptor antagonsts?
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propanolol
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what is the MOA of the thioureas?
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inhibit orgnification and coupling reaction by inhibiting thyroid peroxidase(TPO)
PTU also inhibits peripheral dediodination of T4 to T3. |
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what is the pharacokinectics of the thioureas?
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both are rapidly absorbed
PTU>methimazole both have short half-lives PTU-1.5h methimazole-6h both accumulate in the thyroid both cross placental barrier(PTU less than methimazole) |
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what is the doseing schedule for the thiourease?
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PTU every 6hours
methimazole ever 24 this is because even though they have a short duration of action the effect of their actions last a longer time. ie takes a while for thyroid to rebuild its stores . |
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what are some problems with using thioamides?
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long onset of therapeuitc effect. because it must deplete the thyroid hormone storage pool this can take up to 4-6 weeks
also bc of this there can be some difficulty in making dose predictions so if to high of a dose is used then you could wind up in hypothyroidism |
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what is the use of thioamide therapy?
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palliative relieves symptoms but does not fix the problem
it allows for recover from stimulus of the hyperthyroid state often combined with ablative therapy. |
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what is the toxicity associated with thioamides?
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adverse effects rate of 3-12%
maculopapular pruritic rash(most common) lupus like symptoms most dangerous agranulocytosis(0.3-0.6%) urusally rapidly reversible with cessation liver toxicity cross sensitivity btw thioamides of about 50% therefore if adverse reaction occurs not recommened to switch to other one. |
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what are the monovalent anion inhibitors?
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perchlorate
pertechnetate thiocyanate |
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what are problems of the monovalent anion inhibitors?
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can be overcome by large doses of iodide
can cause aplastic anemia |
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what are the uses of monovalent anion inhibitors?
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Usually used for acute issues rarely used for chronic therapy
perclorate sometimes used in iodide induced thyrotoxicosis such as amiodarone-induced hyperthyroidism |
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what is the MOA of monovalent anion inhibitors?
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competitively block iodide uptake by follicle cells
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what is the woff-chigot effect?
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you only need a few mg of iodide a day if you get more than that into ur system it will actually inhibit thyroid peroxidase and inhibits synthesis of T3 and T4.
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what are the prepartations of Iodide that are given?
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lugols solution(5% Iodine, 10%KI that is reduced to I- in the GI tract)
potassium Iodide Sodium Iodide Potassium Iodide oral solution. |
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what is the MOA of Iodide treatment of hyperthyroidism?
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wolff chaikoff effect
inhibition of the organification of iodide transient main action is to inhibit proteolysis which leads to decreased release of T3 and T4 from the thyroid this is why the onset of action is so fast and ignores the storage pools. |
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What are the benifits of Iodide treatment?
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very fast onset of action
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what are the problems with Iodide treatments?
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only a transient effect. gland rapidley overcomes the wolff chiakoff effect after that inhibition still occurs but less effective.
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How is iodide used in treatment?
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almost always given in conjunction with thioureas which have a very long onset of action but more long lasting effects
benificial in thyoid surgury because it reduces vascularity of the hyperfunctioning thyroid. also used in acute thyroid crisis and severe thyrocardiac disease. |
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what is the toxicity of iodide treatements?
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uncommon and reversible with discontinuation
acneiform rash, drug fever, metalilc taste, bleeding disorders. |
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what is the use of iodinated contrast media?
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used predominantly for diagnosis of thryoid diseases, but it is useful as an adjevant therapy in thyroid storm do to its ability to rapidly inhibit peripheral deiodination as well as suppress T3 and T4 production with longer administration(most likely by same mech as normal iodine)
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what are the two curative treatments of chronic hyperthyroidism?
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surgury and radioactive iodide
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what is the radioactive iodide?
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I131
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what is the MOA of radioactive iodide?
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emitts beta particles that destroy some surrounding follicular tissue. with results in deacresed hormone synthesis and destroyes some of the stores
only penetrates a small distance into the tissue and Iodine is only found in the thyroid so damage is very localized and selective. |
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what is the major drawbacks of usage of radioactive iodide?
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postradiation hypothyroidism
-therefore radioactive therapy usually followed by replacement therapy.usually for rest of life crosses plancetal barrier and is exreted in breast milk. |
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what cell type is targeted by radioactive iodide?
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acinar cells
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What is the role of adrenorecptor blocking agents?
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effects of thryoid are analogous to symptthectic stimulation TH acts a a permissive to adrenergic stimuli
so these can be used to relieve symptoms indirectly. |
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what is the main adrenorecptor blocking agent?
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beta blockers -mainly propranolol
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what is the doseing for propranolol in thyroid conditions?
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20-40mg p.o every 8 hours
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what is the major use of beta blockers in thyroid conditions?
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used to treat symptoms of thryotoxicosis
treates hypertension, tachycardia, atrial fib, and can inhibit peripheral deiodination palliavtive used adjevantly with antithyroid therapies. |
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what is thyroid storm?
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sever acute thyrotoxicosis-life threatening
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what is the treatment of thyroid storm?
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propranolol
iodine(saturated) 10 drops daily PTU(250mg p.o. every 6 hours) antipyretics treatements of cause usually infection |
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what is risk after treating graves disease?
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high level of relapse
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what are the most serious side effects of thioamines drugs
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agranulocytosis(loss of white cells)
liver toxiciy |
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what is the preferred thioamine?
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methinazole due to less side effects
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how is radioactive iodide given
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one dose usually does it
given orally |
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what is the reccomendation of radioacitve iodide with pregancncy?
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countraindicated in preg and breast feeding bc it will cross into this.
even goes farther people on this medication should stay away from children in general |
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why is T4 given more often then T3?
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T4 has longer half life
T4 is regulated by the body to turn into T3 so less chance of causeing hyperthyroid symptoms |
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what is the risk of radioactive iodide with cancer?
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not big risk in older people not seen.
but it is a potential reason not to give to younger people |
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in the US what is the main first line treatment for hyperthyroidism?
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radioactive iodide
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