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thyroid pharm
ENDO
35
Medical
Graduate
11/21/2010

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Term
what are the 2 thyroid secretions?
Definition
93% thyroxine (T4) and 7% triiodothyronine (T3)
Term
what is the cascade of events leading to thyroid hormone secretion?
Definition
the hypothalamus secretes TRH, then the anterior pituitary secretes TSH, then the thyroid secretes T4/T3
Term
what characterizes T4?
Definition
this is the major secretory product of the thyroid and has a relatively long half life (5-7 days) as it functions as the "slow steady" hormone.
Term
what characterizes T3?
Definition
T3 is ~4x as potent as T4 and can be secreted up to 20% of total thyroid output. T4 in the periphery can be converted to T3.
Term
are thyroid hormones bound in the blood?
Definition
yes, both T3/4 bind to TBG and T4 can alternately bind to transthyretin/TBPA. .03% of T4 and .3% of T3 circulate unbound (narrow balance of free TH levels = necessary caution w/drugs that displace this binding such as ASA w/T4).
Term
what can thyroid dysfunction (hyper/hypo) cause changes in?
Definition
growth/development, CV system, GI, skeletal system, neuromuscular, and the reproductive system.
Term
what is the biosynthesis/storage/metabolism from tyrosine -> iodine?
Definition
active transport trapping of I-, synthesis of thyroglobulin, iodination of thyroglobulin tyrosyl residues, coupling of iodotyrosine to form T3/4, proteolysis of thyroglobulin, and deiodination of iodotyrosine and neutralization of the liberated I-
Term
what are the physiologic effects of TH-receptor binding?
Definition
T3R is the primary TH receptor, which T3 has more affinity for than T4 (thus intranuclear T3 determines thyroid status of cells). when the receptor is bound, it forms a complex w/DNA and then affects transcription +/-.
Term
what can hypothyroidism be due to?
Definition
dysfunction of the thyroid, pituitary and hypothalamus
Term
what characterizes primary hypothyroidism? etiologies?
Definition
TH deficiency due to the *thyroid gland. this is diagnosed when TH levels do not increase w/administration of TSH. etiologies: idiopathic hypothyroidism (spontaneous degeneration of gland), hashimotos (chronic autoimmune thyroiditis), radioactive iodine damage (increased risk for lab techs etc), subtotal/total thyroidectomy (tx for hyperthyroidism = *major cause*), and thyroid dysgenesis (sporadic nongoitrous cretinism).
Term
what characterizes secondary hypothyroidism? etiologies?
Definition
TH deficiency due to the *pituitary gland, diagnosed by lack of TSH elevation w/TRH administration (but TSH administration should still increase TH levels). etiologies: pituitary tumors or post-partum infarcts (sheehan's)
Term
what characterizes tertiary hypothyroidism?
Definition
TH deficiency due to the *hypothalamus, which is diagnosed by TSH and TH levels rising w/TRH administration.
Term
what is treatment for hypothyroidism?
Definition
lifelong replacement TH therapy regardless pf etiology/severity
Term
what adverse effects are associated w/TH replacement therapy for hypothyroidism?
Definition
cardiac palpitations, arrhythmias, tachycardia, wt loss, headaches, insomnia, and heat intolerance - all generally due to TH OD and symptoms should subside if meds are withheld for several days. make sure pt is not on ASA or other drugs that interfere w/TBG binding or iodine.
Term
what needs to be factored into treatment of hypothyroid pts w/heart disease or atherosclerosis?
Definition
pts need to be started slowly on therapy so the heart can develop a capacity for increased metabolic demands
Term
what needs to be factored into treatment of secondary hypothyroidism pts?
Definition
b/c secondary hypothyroidism involves the pituitary, the pt will need to be started on cortisol as TH increases the metabolic clearance of adrenocortical hormones and the pt might otherwise develop acute adrenocortical insufficiency.
Term
what needs to be factored into treatment of hypothyroid pts on coumadin/warfarin?
Definition
TH can increase catabolism of the vit K dependent clotting factors, which coumadin/warfarin suppress - so their anticoagulant therapy will need to be lowered.
Term
what needs to be factored into treatment of hypothyroid pts w/DM?
Definition
insulin/oral hypoglycemics may need to be increased as TH will increase metabolic/cellular activity
Term
what needs to be factored into treatment of hypothyroid pts on digoxin for CV disease?
Definition
the digoxin dose must be need to be increased
Term
what is the TH replacement DOC?
Definition
levothyroxine sodium, a synthetic salt version of T4, administration of which may produce normal T3/4 levels. it may also be used to prevent goitrogenic effects of other therapeutic agents.
Term
what is liothyronine sodium?
Definition
a synthetic salt of T3, which is useful as a supplement if a pt is on T4 therapy and not achieving sufficient T3 levels (it has a short half-life, so it is not preferred as a maintenance therapy). it may also be used for a T3 suppression test for hyperthyroidism (T4 levels should depress w/T3 administration) or short term suppression of a solitary thyroid nodule before a radioactive iodine scan.
Term
what is liotrix?
Definition
a 4:1 mix of levothyroxine:liothyronine, which is really only necessary for hypothyroid pts who can't take the extra liothyronine/T3 pill
Term
what is thyroid USP?
Definition
ground up, dehydrated animal thyroid glands put into capsule form - however there is no consistency in T3:T4 levels, so it is seldom used.
Term
what is thyroglobulin?
Definition
extract of frozen pig thyroid, which has both T3/4 - but similar to thyroid USP, it is seldom used.
Term
what are the different etiologies which can cause hyperthyroidism/thyrotoxicosis? tx?
Definition
graves disease, toxic multinodular goiter, thyroiditis, and single hyperfunctioning thyroid nodules. tx: decrease TH secretion via direct inhibition of release, tissue reduction (sx/radiation), and inhibition of synthesis.
Term
what is a thyroid storm? tx?
Definition
massive TH release due to trauma, infection, inadequate prep for thyroid sx, or idiopathic. tx: sedations, O2 support, decrease body temp, antithyroid meds, iodine, corticosteroids, fluids, electrolytes, and beta-blockers
Term
what are propyluracil and methylthiouracil?
Definition
these thiourea derivatives will both interfere w/incorporation of iodine into thyroglobulin - reducing TH synthesis. propyluracil can also inhibit coupling of iodotyrosine to form T3 and T4 and decreases conversion of T4 to T3 in periphery, but otherwise neither has much effect on existing TH. half-life: 9 hrs.
Term
what is methimazole?
Definition
methimazole is similar to propyluracil in its action but more potent (10x) and w/a longer half-life. methimazole also *will not inhibit T4 -> T3 conversions in the periphery. (carbimazole: european pro-drug version)
Term
what ADRs are associated w/the TH synthesis inhibitors (propyluracil, methylthiouracil, and methimazole)?
Definition
cholestatic jaundice, psychosis, lymphadenopathy, lupus-like syndrome, and granulocytopenia/agranulocytosis (very serious)
Term
what is potassium perchlorate?
Definition
a drug which inhibits the anionic pump, keeping iodine from being transported into the thyroid. no longer used b/c potassium perchlorate can cause fatal aplastic anemia.
Term
what is potassium iodide?
Definition
transiently inhibits the organic iodine formation -> blocks hormone release. this is commonly used to block accumulation of radioactive iodine as seen in nuclear power plant accidents.
Term
what is lithium carbonate?
Definition
this temporarily prevents release of iodine from the thyroid gland and therefore is not used as an anti-hyperthyroidism agent. it is however used to treat bipolar disorder, so pts on it need to have their thyroid status monitored (can cause hypothyroidism).
Term
what is iodine 131?
Definition
in microcurie amounts this is used diagnostically and in millicurie amounts this is used for selective destruction via beta particle emissions.
Term
why would beta-blockers be used in hyperthyroidism?
Definition
as temporary adjunct tx for symptoms of hyperthyroidism (tachycardia, arrhythmias, etc) to stabilize the CV while bringing down thyroid levels. contraindications: DM (beta blockers cause hyperglycemia) and asthmatic/COPD (beta blockers worsen respiratory condition)
Term
can an iodine OD cause hypothyroidism?
Definition
yes, due to negative feedback
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