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tx of thyroid disorders
pharm 2 module 1
55
Medical
Graduate
09/03/2009

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Term
what is a protein that binds >99% of thyroid hor in plasma? what are 2 other proteins that transport hormones in blood?
Definition
thyroid-binding globulin (tbg). also, thyroid-binding pre-albumin (tbpa), and albumin
Term
where is t4 converted to t3?
Definition
in cells. t3 activates nuclear receptors, followed by increase in rna and protein synthesis
Term
Who should be screened for hypothyroidism?
Definition
all newborns, all adults every 5 yrs starting at age 35
Term
Does amiodarone cause increased or decreased raiu (radioactive iodine uptake)?
Definition
decreased
Term
Does thyroiditis cause increased or decreased raiu (radioactive iodine uptake)?
Definition
decreased
Term
Does ectopic thyroid tissue cause increased or decreased raiu (radioactive iodine uptake)?
Definition
decreased
Term
Does exogenous thyroid hormone cause increased or decreased raiu (radioactive iodine uptake)?
Definition
decreased
Term
Does iodinated radiocontrast dye cause increased or decreased raiu (radioactive iodine uptake)?
Definition
decreased
Term
Does grave's dz cause increased or decreased raiu (radioactive iodine uptake)?
Definition
increased
Term
Does tsh-secreting tumors cause increased or decreased raiu (radioactive iodine uptake)?
Definition
increased
Term
Does pituitary resistance to t4 cause increased or decreased raiu (radioactive iodine uptake)?
Definition
increased
Term
Do trophoblastic dz cause increased or decreased raiu (radioactive iodine uptake)?
Definition
increased
Term
Does a toxic adenoma cause increased or decreased raiu (radioactive iodine uptake)?
Definition
increased
Term
Does a multinodal goiter cause increased or decreased raiu (radioactive iodine uptake)?
Definition
increased
Term
50 y/o woman with 15 lb weight loss
c/o insomnia, muscle weakness, leg swelling, dysphagia, eyes “stick out”
PE: HR 100 bpm, mild proptosis, enlarged thyroid gland, 2+ pitting edema.
TSH < 0.02 mIU/mL and T4 18.2 mcg/dL

What drug, dose, schedule, and duration of therapy is most appropriate to treat this patient?

What parameters would you monitor to evaluate efficacy and safety?
Definition
Antithyroid Medications
Thionamides
Propylthiouracil (PTU)
Methimazole
Iodides
Radioactive iodine (RAI)
Surgery (subtotal thyroidectomy)
Adjunctive Pharmacotherapy
beta-blockers
Term
What is the moa of methimazole (tapazole)?
Definition
blocks organification of iodides and inhibits coupling of MIT and DIT ->
Decreases thyroid hormone production
Term
What are the 2 thionamides and what do they tx?
Definition
ptu, methimazole (tapazole), hyperthyroidism
Term
What is the moa of Propylthiouracil (PTU)?
Definition
blocks organification of iodides and inhibits coupling of MIT and DIT.
Also inhibits peripheral T4 to T3 conversion
Term
What is the drug of choice in pregnancy/lactation, thyroid storm?
Definition
Propylthiouracil (PTU)
Term
Pt on ptu develops agranulocytosis, aplastic anemia, arthralgias, lupus-like syndrome, and hepatotoxicity. Should you switch to methimazole?
Definition
DO NOT TRY OTHER AGENT!!
Term
The following are major s/e of what drug class: aplastic anemia, arthralgias, lupus-like syndrome, and hepatotoxicity.
Definition
thionamides. agranulocytosis is also a major s/e.
Term
agranulocytosis is associated w/what drug class?
Definition
thionamides
Term
Pt on ptu develops pruritic maculopapular rash, arthralgias, fever, benign transient leukopenia. Should you try methimazole?
Definition
may try other agent, cross sensitivity ~50%
Term
The following are s/e of what drug class: pruritic maculopapular rash, arthralgias, fever, benign transient leukopenia?
Definition
minor ade of thionamides
Term
how long does it take to normalize ft4 and tsh levels after administration of thionamides? when should you re-run ft4 levels?
Definition
Symptoms and hormone levels normalize in 4-8 weeks.
Monitor FT4 4-6 weeks after initiation of therapy and after dose changes.
FT4 normalizes after 4-8 weeks but TSH may remain suppressed for several months after euthyroid
Term
once a pt is euthyroid, how frequently do you reassess tft's?
Definition
every 3-6 mos
Term
what are 3 labs you run when starting a pt on thionamides?
Definition
baseline ft4, tsh, and cbc w/diff
Term
what is the remission rate w/thionamides?
Definition
40-50%
Term
what are 2 iodine tx for hyperthyroidism?
Definition
Lugol’s solution (6 mg/drop) or saturated potassium iodide solution (SSKI, 38 mg/drop)
Term
what is the moa for iodine?
Definition
MOA: acutely blocks thyroid hormone release, inhibits thyroid hormone synthesis, decreases gland vascularity
Term
hsn rxns, burning mouth, gi upset, and gynecomastia are ade of what drug?
Definition
iodine. iodism is metallic taste, burning mouth, gi upset
Term
what is Used pre-operatively before thyroid surgery or after RAI treatment?
Definition
iodine
Term
what drug can be used for people exposed to radiation? What are the 2 fda-approved products?
Definition
Potassium iodide competitively inhibits uptake of radioactive iodine. thyro-block, losat. Risk of developing thyroid cancer after exposure to radioactive iodine is greatest in neonates, infants, and small children.
The risk is smallest in adults > 40 years old
Term
What is now the most common t of hyperthyroidism?
Definition
rai and sx
Term
what is the moa of rai?
Definition
MOA: incorporated into thyroid hormones and thyroglobulin leading to follicular necrosis
Term
what is the major ade of rai?
Definition
hypothyroidism
Term
what is often required w/rai?
Definition
Often requires concomitant antithyroid/adjunctive agents
Term
how effective is rai?
Definition
Remission: 60% within 6 months, another 40% in 1 yr with additional doses
Term
what is the moa of beta-blockers?
Definition
MOA: block beta-adrenergic receptors and partially block conversion of T4 to T3 to ameliorate thyrotoxic symptoms
Term
what is an adjunctive tx for hyperthyroidism?
Definition
beta-blockers (commonly propranolol)
Term
when is propranolol contraindicated?
Definition
Contraindicated with CHF, bradycardia, caution with asthma, COPD, DM
Term
What is a Life threatening medical emergency with
Severe thyrotoxicosis, high fever, tachycardia, tachypnea, dehydration, delirium N/V/D that is
Precipitated by infection, trauma, surgery, RAI, withdrawal of antithyroid meds? how is it tx?
Definition
thyroid storm. Treatment includes:
PTU, iodides, propranolol, corticosteroids, and supportive measures
Term
BR is a healthy, 65 y/o woman without complaints
Elevated TSH (6-7.5 mIU/ml), normal T3, FT4


What thyroid disorder does this patient have? Potential risks involved?

Is thyroid hormone replacement indicated?
Definition
Term
what is the drug of choice for hypothyroidism?
Definition
Levothyroxine (Synthroid, Levoxyl, Unithroid, etc.)
Term
is Levothyroxine (Synthroid, Levoxyl, Unithroid, etc.) t3 or t4?
Definition
synthetic t4
Term
What initial dose of levothyroxine would you recommend for a 55 y/o, 75 kg male with a PMH of GERD, HTN, hyperlipidemia and angina?

A) 25 mcg daily
B) 50 mcg daily
C) 0.050 mg daily
D) 100 mcg daily
E) 125 mcg daily
Definition
Term
What are 3 enzyme inducers that cause Increase in thyroid hormone?
Definition
Rifampin
Carbamazepine
Phenytoin
Term
what are 4 substances that cause Impaired absorption of thyroid hormone?
Definition
Iron, antacids, calcium, and sucralfate
Term
what drug causes Inhibition of conversion from T4 to T3?
Definition
Amiodarone
Term
What is a Synthetic T3 that is
Used diagnostically for T3 suppression test and has a
t ½ ~1.5 days with the following
Disadvantages: cost, increased cardiac adverse effects, monitoring?
Definition
Liothyronine (Cytomel)
Term
What is a synthetic t4:t3 in a 4:1 ratio?
Definition
Liotrix (Thyrolar, Euthyroid).
Predictable potency, expensive, ? therapeutic rationale – majority of studies show no benefit over levothyroxine
Term
what is Derived from hog, beef or sheep thyroid glands and has a
Variable ratio of T4 and T3?
Definition
thyroid usp (armour and generic). Inexpensive, unpredictable hormonal stability, antigenic.
Rarely used except in older, stable patients who won’t switch to a newer product
Term
how do dose requirements for hpothyroidism meds change w/age and pregnancy?
Definition
Dose requirements increase in pregnancy; monitor TSH every trimester.
Dose requirements may decrease with age
Term
55 y/o, 70 kg female with HTN
c/o weight gain, fatigue, constipation, cold hands/feet
PE: dry skin, coarse hair
Meds: lisinopril, HCTZ, ASA, Maalox prn (~6x/wk)
Labs: TSH 12.6 mIU/mL, FT4 0.7 ng/dL

What drug therapy would you recommend? Initial dose?
Dosing instructions/counseling points?

What lab parameter would you monitor for efficacy? When?
Definition
Term
what is End stage of uncontrolled, long-standing hypothyroidism with
Advanced hypothyroid symptoms, hypothermia, delirium, and coma? How do you tx?
Definition
myxedema coma. Needs aggressive treatment with IV thyroxine, glucocorticoids, and supportive measures.
Levothyroxine 400-500 mcg IV x 1;
300 mcg if cardiac disease,
Then 50-100 mcg/day IV.
Improvement of symptoms within 24 hrs.
Switch to oral levothyroxine once the patient is stable
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