module 2 lecture 2 Flashcards by Matti Daniel

What are the two types of thyrroid hormones

thyroxine (T4) and triiodothyronine (T3)

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Which thyroxine is produced more? which is more potent?

T4 is produced 10x more
T3 is more potent

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What are the 4 physiological effects of thyroid hormones

Growth and development
metabolism
thermogenesis
CV effects

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Absent T3 can cause

cretinism

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how does thyroid hormone affect growth and development

Promotes protein sythesis and brain development

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is thyroid hormone anabolic or catabolic?

BOTH! anabolic at normal concentrations, catabolic at hyperthyroid levels

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How does thyroid hormone affect metabolism

It increases the basal metabolic rate and O2 consumption

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How does thyroid affect thermogenesis

Increases the resting heat production
Inability to adjust temperatures is a symptom of both hyper and hypo thyroidism

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effect of thyroid hormone on cardiovascular symptoms

increases catecholamine sensitivity (epinephrine norepinephrine etc) leading to rapid HR

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1st step of thyroid hormone synthesis (where does this take place?)

Dietary iodine (I2) to iodide (i-) in stomach

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second step of thyroid hormone synthesis

iodide is actively transported into the cell by NIS (Na I symporter)

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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

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4th step of thyroid synthesis

Iodide free thyroglobulin is transported to the apical membrane

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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.

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6th step of thyroid synthesis

MIT + DIT or
DIT+DIT will for T3 and T4 respectively.

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7th step of thyroid synthesis

thyroid hormone containing thyroglobulin is retrieved back to cytosol by pinocytosis

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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

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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

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How to distinguish toxic goiter from non-toxic goiter

Toxic goiters are hyper thyroidic. they produce a lot of thyroid hormones.

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What are the ways thyroid is transported in plasma

TBG
transthyretia
albumin

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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

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T4 is converted to T3 by

5 ‘ deionidase

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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

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Symptoms of hypothyroidism

low metabolic rate (fatigue, mental fullness)
defective thermoregulation (cold)
non-toxic goiter
dwarfism or cretinism

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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?

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