Thyroid - DONE Flashcards
What stimulates the release of thyroid hormones?
Thyroid releasing hormone (TRH) from hypothalamus is secreted into the capillaries of the pituitary portal venous system, and in the anterior pituitary gland, TRH stimulates the synthesis and release of THYROTROPIN (thyroid stimulating hormone) TSH. TSH in turn stimulates an adenylyl cyclase mediated mechanisms in the thyroid cell to increase the synths and release of T4 & T3.
What are the two hormones produced by the thyroid gland derivatives of?
iodinated derivatives of tyrosine
What is the ratio or T4 to T3 produced in the thyroid gland?
5:1 ratio of T4 to T3
What is most of circulating T3 derived form?
deiodination of T4 by 5’deiodinase
What combines in the thyroglobulin molecule to form thyroxine (T4)?
two molecules of DIT (diiodotyrosine)
**at the apical cell membrane, iodide is oxidized by thyroidal peroxidase to iodine, in which form it rapidly iodinates tyrosine residues within the thyroglobulin molecule to form MIT & DIT.
Monoiodotyrosine & Diiodotyrosine
What combines in the thyroglobulin molecule to form triiodothyronine (T3)?
1 molecule of MIT and 1 molecule of DIT
***at the apical cell membrane, iodide is oxidized by thyroidal peroxidase to iodine, in which form it rapidly iodinates tyrosine residues within the thyroglobulin molecule to form MIT & DIT.
Monoiodotyrosine & Diiodotyrosine
What is the primary pathway for the peripheral metabolism of thyroxine (T4)?
deiodination
What does the deiodination of thyroxine (T4) produce?
T3, which is more potent than T4, and rT3
*rT3 is metabolically inactive
What two proteins are T3 and T4 bound to in the serum?
Thyroxine binding globulin (TBG) - primarily
Also can be found bound to Albumin
What is the potency ratio of active T3 to T4 ?
T3 is in the active form = 4:1 potency of T3:T4
What is the oral bioavailability of current preparations of thyroxine (T4)?
80%
What is the oral bioavailability of current preparation of T3?
95%
Where is Thyroixine absorbed best?
duodenum and ileum
What is the effect of hyper and hypothyroidism on the half life of T3/T4?
Hyperthyroid - decreases T1/2
Hypothyroid - increases T1/2
How long is the half life of T4 in a euthyroid patient?
7 days
How long is the half life of T3 in a euthyroid patient?
1 day
What kind of drugs will cause an increase in metabolism of T4 and T3?
P450 inducers
-from book below:
rifampin, phenobarbital, carbamezepine, phenytoin, tyrosine kinase inhibitors, HIV protease inhibitors)
How do euthyroid patients maintain plasma concentration when given P450 inducers?
by increasing thyroid funciton
What will a hypothyroid patient require when given a P450 inducer?
may require more T4
What is increased by pregnancy, estrogens, or oral contraceptives?
TBG (thyroxine-binding globulin)
What does increased TBG (thyroxine-binding globulin) cause?
a decrease in free hormone
- a shift from free to bound
- found in pregnancy, estrogens, or oral contraceptives
What does a nuclear receptor bind?
ONLY T3
* effects mediated by alterations in gene expression.
What are the three synthetic preparations used to treat Hypothyroidism?
Levothyroxine
Liothyronine
Liotrix
What is the thyroid preparation of animal origin used to treat hypothyroidism?
Desiccated Thyroid
What are the 5 antithyroid agents used to treat hyperthyroidism?
- Thioamides
- Iodides
- Anion Inhibitors
- Radioactive Iodine
- Adrenoceptor antagonists
What is the drug of choice for thyroid replacement and suppression therapy?
Levothyroxine
Why is Levotyroxine the DOC for thyroid replacement and suppression therapy?
T4 is administered when pt is given Levothyroxine
- Low Cost
- Long T1/2 = 7 days
- Given Once Daily
….from book: T4 is converted to T3 intracellularly; thus administration of T4 produces both hormones.
lack of allergenic foreign protein also
Why is Liothyronine not preferred over Levothyroxine for routine replacement therapy?
Because of its shorter half life (24 hours), so you would have give multiple daily dosing, and higher costs
Which is more potent, Levothyroxine or Levothyronine?
Levothyronine is more potent than Levothyroxine (3-4X)
What specific patients should Levothyronine be avoided in?
patients with CARDIAC DISEASE
because of its greater hormone activity, and consequent greater risk in cardiotoxicity
What is Levothyronine best used for?
- Liothyronine is administration of T3
answer: it is best used for short term suppression of TSH
Which drug used for treatment of Hypothyroidism administers T4 and T3? What is the ratio of T4 to T3?
Liotrix
*4:1 of T4:T3
?i didn’t know how to ask this??
Which Thyroid preparation for treatment of hypothyroidism is disadvantageous due to its protein antigenicity?
Desiccated Thyroid (Animal Origin)
From the Book: What is the shelf life of synthetic thyroid preparations?
2 years
– particularly if they are stored in dark bottles to minimize spontaneous deiodination
Which antithyroid therapy blocks hormone production AND DECREASES TISSUE RESPONSE?
Thioamides
Which antithyroid therapy destroys the thyroid gland?
Radioactive Iodine
Which antithyroid therapy is an adjunctive therapy?
adrenoceptor antagonist
Which three antithyroid therapy agents block hormone production?
1 Thioamides
- Iodides
- Anion Inhibitors
What are the 3 effects of antithyroid agents?
- decrease hormone production
- decrease tissue response
- Destroy gland
What is the GENERAL strategy for management of Hypothyroidism?
Replacement Therapy
What is the DOC for replacement therapy for hypothyroidism?
Levothyroxine
brand or generic prep is fine
T/F Combination of Levothyroxine and Liothyronine has no therapeutic benefit than Levothyroxine alone.
true
What do hypothyroid infants require more per kilogram of body weight than hypothyroid adults?
T4
What is the average dosage of Levothyroxine for infants 1-6 months?
10-15 mcg/kg/d
What is the average dosage of Levothyroxine for adult?
1.7 mcg/kg/d
Who many require less thyroxine for replacement?
older adults (>65)
T/F Levothyroxine dosage is highly patient specific because of the variability in the absorption of thyroxine.
true
How many times a day should Levothyroxine be administered? how?
- Once daily (because of its long half life of 7 days)
- on an empty stomach
(30 min before meal or 1 hour after)
How long does it take a starting dose Levothyroxine to reach steady-state levels? How does this effect dosing?
6-8 weeks
Dosage changes should be made slowly.
*Start low and titrate up to euthyroid or toxicity will occur
What should be measured at regular intervals to ensure successful therapy and avoid toxicity when administering Levothyroxine?
Serum TSH and Free Thyroxine
What is the optimal range of TSH?
0.5 - 2.5 mU/L for TSH
What is imperative to monitor in patients taking Levothyroxine, especially elderly patients?
Cardiac Toxicity
- Book: the heart is very sensitive to level of circulating thyroxine, and if angina pectoris or cardiac arrhythmia develops, it is essential to stop or reduce the dose of thyroxine immediately.
A child presents with restlessness, insomnia, and accelerate bone maturation and growth. After reviewing her patient history you see that she is taking Levothyroxine. What is our diagnosis?
Thyroxine toxicity
An adult presents with increased nervousness, heat intolerance, episodes of palpations, tachycardia, and weight loss. After reviewing his patient history you see that he is taking Levothyroxine. What is your diagnosis?
Thyroxine toxicity
What should you test to confirm Thyroxine toxicity?
TSH - which will determine whether the symptoms are due to excess thyroxine in the blood.
What is the most common cause of Hypothyroidism?
Hashimoto’s Thyroiditis
Does the presence of a goiter diagnose hypo vs. hyperthyroidism?
NO!
Hypothyroidism can be with or without a thyroid enlargement (goiter)
Elevated TSH but normal T4/T3 levels =
Subclinical Hypothyroidism
*thyroid is compensating
End state of untreated hypothyroidism?
Myxedema coma
- sever hypothyroidism
Book: Progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock and death are symptoms of what?
Myxedema coma
- give all preparations IV
- avoid excessive water intake therefore use caution with IV
Book: What is the treatment of choice for Myxedema Coma?
loading dose of Levothyroxine IV - usually 300-400 mcg initially…… followed by 50-100 mcg daily.
What can drug induced hypothyroidism be satisfactorily managed with?
levothryoxine therapy if the offending agent cannot be stopped
Removal of the offending agent (drug) usually enough to treat drug induced hypothyroidism. What drug causing hypothyroidism would cause a need to use thyroid therapy even after removal the drug?
Amiodarone -
Levothyroxine therapy may be necessary even after discontinuation of amiodarone because of amiodarones very long half life.
what are the two thioamide drugs? What are these used for?
methimazole & propylthiouracil (PTU)
Thyrotoxicosis
Which Thioamide drug is more toxic?
Methimazole is 10 X more potent than propylthiouracil
Due to black box warning, when should propylthiouracil (PTU) be used?
first trimester of pregnancy, in thyroid storm, an din those experiencing adverse reactions to methimazole
How is methimazole absorbed?
completely, but at variable rates
What is the half life of Methimazole compared to PTU?
Methimazole = T1/2 - 6 hours
Propylthiouracil (PTU) = T1/2 - 1.5 hours
How is propylthiouracil absorbed? bioavailability?
rapidly absorbed, reaching peak serum levels after 1 hour
bioavailability = 50-80%
How do you dose methimazole compared to Propylthiouracil (PTU)?
Methimazole = single daily dose @ 30 mg for mild to moderate hyperthyroidism
Propylthiouracil (PTU) = dosing every 6-8 hours
**both are taken up by the thyroid gland
Both thioamides cross the placental barrier, which of the two is preferred during the first trimester of pregnancy?
Propylthiouracil , because it is more strongly protein bound, and therefore crosses the placenta less readily.
What is the major mechanism of action of thioamides?
inhibit thyroid peroxidase catalyzed reactions and blocking iodine organification
**DO NOT BLOCK IODIDE UPDATE
Which thioamide prevents peripheral conversion of T4 to T3?
PTU …..
Methimazole DOES NOT
What is the most common adverse effects of thioamides?
most common is a maculopapular pruritic rash, less common are headache, nausea, pain/stiffness of joints
What is the most serious adverse effect of thioamides?
agranulocytosis/leukopenia
most common in older adults and those on METHIMAZOLE
Which antithyroid agent inhibits organification and hormone release causing a decrease in size and vascularity of thyroid gland?
Iodides
What is the primary mechanism of action of Iodides at therapeutic doses?
decreased hormone release
Iodides are useful in decreasing the size and vascularity of thyroid. What is a good use of Iodides because of this reason?
Preoperative use
Should Iodide be used alone? Why or Why not?
Iodide should NOT be used alone, because the gland will escape from the iodide block in 2-8 weeks.
This “REBOUND” or “ESCAPE” often occurs in 2-8 weeks because of INCREASED TSH.
Book: what antithyroid agent block uptake of iodide by thyroid gland through competitive inhibition of the iodide transport mechanism, but this CAN BE OVERCOME by large amounts of iodides?
Ionic Inhibitors
Thiocyanate - (SCN-)
Perchlorate - (ClO4-)
Slides:
Monovalent anions that are actively accumulated by the thyroid and inhibit Na/I pump?
Ionic Inhibitors
Thiocyanate
Perchlorate
What two diseases are ionic inhibitors (thiocyanate and perchlorate) used to treat clinically?
Treatment of Graves’ disease and amiodarone-induced thyrotoxicosis
Why is perchlorate rarely used clinically?
because it can cause aplastic anemia
What is the only isotope used to TREAT thyrotoxicosis? (hint: all the other ones are used to diagnose) How do you administer this agent?
Radioactive Iodine 131I - administered orally
Radioactive Iodine 131I is administered orally, irapidly absorbed and concentrates where?
THYROID GLAND
Book: also incorporated into storage follicles
What is the mechanism of action of 131I?
Its therapeutic effect depends on
EMISSION OF BETA RAYS that DESTROY Glandular tissue
What is the half life of Radioactive Iodine I131?
T1/2 = 5 days
What is the penetration range of Radioactive Iodine 131I?
400-2000 um
Who is radioactive iodine 131I contraindicated in?
pregnancy or nursing mothers
book: because it crosses the placenta and destroys fetus thyroid gland and is excreted in breast milk
What are the advantages of Radioactive Iodine 131I?
cheap, easily administered, effective, painless
What are used to treat the SYMPTOMS associated with thyrotoxicosis? ( usually in thyrotoxic crisis)
- adrenoceptor blocking agents
- calcium channel blockers
- Glucocorticoids
What are the most common adrenoreceptor blocking agents used in treating symptoms associated with thyrotoxicosis?
Beta Blockers without intrinsic sympathomimetic activity (metoprolol, PROPANOLOL, atenolol)
What three specific symptoms do adrenoceptor blocking agents, Beta Blockers, treat in thyrotoxicosis?
control Tachycardia, Hypertension, and atrial fibrillation
Which Beta Blocker may prevent conversion of T4 to T3 in the periphery?
Propanol
what are the three primary methods of treating Graves’ disease?
- antithyroid drug therapy
- thyroidectomy
- Radioactive iodine
What is the treatment of a single toxic adenoma?
surgical excision or radioactive iodine
What is the treatment of a toxic multinodular goiter?
antithyroid drug therapy followed by subtotal thyroidectomy
Book: best treated with the antithyroid drug methimazole (preferable) or propylthiouracil followed by subtotal thyroidectomy
What is termed spontaneously resolving hyperthyroidism?
Subacute Thyroiditis
Book: During the a viral infection of the thyroid gland, there is destruction of thyroid parenchyma with transient release of stored thyroid hormones. What is the describing?
Subacute Thyroiditis
What is the treatment for Subacute Thyroiditis?
Usually resolves on its own, but supportive therapy for symptoms can be used, Beta Blockers without intrinsic sympathomimetic activity (Propanolol) for tachycardia and aspirin and non steroidal anti-inflammatory drugs to control local pain
Treatment of thyroid storm
antithyroid drugs therapy and adjunctive therapy
treatment of ophthalmopathy?
surgical excision or radioactive iodine therapy
treatment of thyrotoxicosis during pregnancy?
typically administered propylthiouracil (PTU)
–dosage kept at a minimum
What is the treatment of Neonatal Graves’ disease?
PTU (Propylthiouracil), Lugol’s solution, and Propanolol
Medication is reduced as clinical signs improve (usually discontinued in 6-12 weeks)
What is the treatment of Amiodarone -induced thyrotoxicosis?
- remove amiodarone if possible
- 2 types: type 1 (iodine induced) and type 2 (inflammatory)
How do you treat type 1 amiodarone - induced thyrotoxicosis?
thioamides
How do you treat type 2 thyrotoxicosis?
glucocorticoids
Due to difficulty distinguishing between type 1 and type 2 amiodarone thyrotoxicosis, how is it typically treated?
typically treated with both thioamides and glucocorticoids togehter
