module 2 lecture 2 Flashcards
What are the two types of thyrroid hormones
thyroxine (T4) and triiodothyronine (T3)
Which thyroxine is produced more? which is more potent?
T4 is produced 10x more
T3 is more potent
What are the 4 physiological effects of thyroid hormones
Growth and development
metabolism
thermogenesis
CV effects
Absent T3 can cause
cretinism
how does thyroid hormone affect growth and development
Promotes protein sythesis and brain development
is thyroid hormone anabolic or catabolic?
BOTH! anabolic at normal concentrations, catabolic at hyperthyroid levels
How does thyroid hormone affect metabolism
It increases the basal metabolic rate and O2 consumption
How does thyroid affect thermogenesis
Increases the resting heat production
Inability to adjust temperatures is a symptom of both hyper and hypo thyroidism
effect of thyroid hormone on cardiovascular symptoms
increases catecholamine sensitivity (epinephrine norepinephrine etc) leading to rapid HR
1st step of thyroid hormone synthesis (where does this take place?)
Dietary iodine (I2) to iodide (i-) in stomach
second step of thyroid hormone synthesis
iodide is actively transported into the cell by NIS (Na I symporter)
third step of thyroid synthesis (where does this take place?)
In the follicular cell, iodide passes down its electrochemical gradient and into the follicular colloid. It is oxidized by thyroid peroxidase to I 0 at apical membrane
4th step of thyroid synthesis
Iodide free thyroglobulin is transported to the apical membrane
5th step of thyroid synthesis
Thyroglobulin is iodinated by thyroid peroxidase at one or two positions forming the hormone precursors monoiodotyrosine (MIT) and diiodotyrosine (DIT) This step is called iodide organification.
6th step of thyroid synthesis
MIT + DIT or
DIT+DIT will for T3 and T4 respectively.
7th step of thyroid synthesis
thyroid hormone containing thyroglobulin is retrieved back to cytosol by pinocytosis
8th and final step of thyroid synthesis
Lysosomal exopeptidases cleave T4 (or T3) from thyroglobulin. The hormone is then released into circulation where T4 can be converted to more active T3 by 5 deiodinase
hypothalamus- pituitary-thyroid axis
hypothalamus
! TRH
anterior pituitary
! TSH
thyroid glabd
!
T4 and T3
T4 and T3 have a negative feedback loop on anterior pituitary and hypothalamus
How to distinguish toxic goiter from non-toxic goiter
Toxic goiters are hyper thyroidic. they produce a lot of thyroid hormones.
What are the ways thyroid is transported in plasma
TBG
transthyretia
albumin
transport proteins have greater affinity to T3 or T4?
What percent of T4 is free?
Which one has a longer half life? T3 or T4?
Which one has a more rapid onset?
Greater affinity to T4
0.04 % is free
T4 has a longer half life
T3 has a more rapid onset
T4 is converted to T3 by
5 ‘ deionidase
In excretion via bila, T4 can be converted into ____ &_____. T3 can be converted into _____
T3 active or rT3 (inactive)
T3 can be inactivated by converting to 3’ T2
Symptoms of hypothyroidism
low metabolic rate (fatigue, mental fullness)
defective thermoregulation (cold)
non-toxic goiter
dwarfism or cretinism
What is the most common cause of hypothyroidism
Hashimotos thyroiditis
What is hashimotos thyroiditis
Most common cause of hypothyroidism that is caused by an autoimmune disease that destroys your thyroid glands.
Symptoms of hyperthyroidism
Excessive metabolism (always hot and losing weight)
increased HR and vascular output
What is the most common cause of hyperthyroidism
Graves disease
What is graves disease
Most common autoimmune thyroid stimulating IgG .
What are some drugs used in Thyroid hormone replacement therapy (hypothyroidism)
Levothyroxine (T4)
Liothyrionine (T3)
Liotrix
Levothyroxine (T4) characteristics
Converted to T3 intracellularly
slow onset, long half life (7-days)
takes 6-8 weeks to reach steady state levels
Liothyronine (T3) characteristics
Rapid onset, short duration of action (24 hrs)
greater risk of vardiotoxicity
Liotrix characteristics
4:1 mixture of T4 & T3, more expensive
not shown to be more effective that T4 alone.
What are some treatment options for hyperthyroidism
Thioamides
I 131
Iodide
What are some thioamide drugs
Methimazole, propylthiouracil
how do thioamides work in hyperthyroidism?
they inhibit thyroid peroxidases
(this blocks iodine organification and coupling of iodotyrosines)
slow onset
How does I 131 work in treating hyperthyroidism? how is it administered?
localized destruction of thyroid follicles
administered orally as Na 131 I
issues with 131 I
hypothyroidism occurs in 80% of patients and includes a potential increase in certain cancers
How does Iodide treat hyperthyroidism
large doses of I- inhibit its own uptake. iodide large doses inhibit thyroide synthesis and release .
Can iodide be used long term for hyperthyroid treatment?
No
what is the most sensitive index for hyperthyroidism and the gold standard for testing
TSH test
Which test is the most accurate
Free T4 (may be normal in mild thyroid)
What are the tests of autoimmunity
ATgA
TPO-Ab
TRAb
Does low or high TSH indicate hyperthyroidism
Low
does low or high FT4 indicate hyperthyroidism
High
What are the 4 causes of drug induced hyperthyroidism
Iodinated cpds
Amiodarone
Interferon a &b
Li
What are 3 treatments for hyperthyroidism
Thioamides (propylthiouracil, methimazole)
Radioactive iodine
Surgery
Which thioamide drug has a longer half life
Methimazole
What is the dosing for the thioamide drugs
Daily for methimazole, Q 8-12 hrs for PTU
Which thioamide drug blocks T4->T3 conversion
PTU
what trimesters can the thioamide drugs be used
PTU-1st trimester
Methimazole- 2n and 3rd trimester
Which thioamide drug is preferred in lactation
Methimazole
Which thioamide drug is more potent
methimazole
Which thioamide drug has a black box warning
PTU- hepatic failure
Initial PTU dosing
50-150 mg TID
Initial methimazole dosing
Free T4 1-1.5x ULN 5-10
Free T4 >1.5-2x ULN 10-20
Free T4 > 2x ULN 30-40
What is the maintenance dose for methimazole
5-15 mg/day
Maintenance dosing for PTU
50 mg BID or TID
MAX dosing PTU
1200 mg/day
MAX dosing for methimazole
60 mg/day
Thioamide adverse effects
GI upset, nausea, vomiting
rash (wheals, hive, SOB)
Agranulocytosis (If neutrophil drops below 500 d/c immediately)
Hepatitis
RAI absolute contraindications
Pregnant or Nursing
When can we use B blockers for hyperthyroidism
Only for short term to control symptoms. HR>90 BPM
what are some cardio selective b blockers for hyperthyroidism
propanolol (partially blocks T4->T3 conversion)
metoprolol
atenolol
When should we use calcium channel blockers instead of b blockers for hyperthyroidism
bronchiospasms
What are some calcium channel blockers
Diltiazem or verapamil
What agents should we avoid when treating hyperthyroidism with B blockers
Agents with sympathomimetic activity
(acebutolol, carteolol, penbutolol, pindolol)
What are some thyroid supplements for hypothyroidism
Levothyroxine (T4)
Liothyronine (T3)
Desiccated thyroid
Name levothyroxine drugs
Tirosint, synthroid, levoxyl, unithyroid
Liothyronine (T3) drugs
Cytomel, triostat
Desiccated thyroid drug name
Armour thyroid
First choice of treatment for hypothyroid patients
levothyroxine
Blackbox warning for Levothyroxine
In euthyroid patients, thyroid supplements are ineffective for weight loss.High doses may produce life threatening toxic effects
How does levothyroxine help hypothyroidism
Converts T4 to T3. It provides necessary hormone without bolus effect of T3. Long half life allows for daily dosing.
Patient counseling for levothyroxine
Take on an empty stomach (60 min before breakfast) or 4 hr after eating before bed
