• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/62

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

62 Cards in this Set

  • Front
  • Back
Immediate precursors to T3 and T4?
immediate precursor:
3-monoiodotyrosine (MIT)
3,5-diiodotyrosine (DIT)

-MIT and DIT couple to give T3 or T4
-T4 has low affinity for T3 receptor, therefore in periphery its converted to T3 to give the active form
reverse T3
-reverse T3 is form of T3 that is formed in the periphery
-rT3 binds to the receptor very weakly – its function, if any, is not known. Large amounts are made during chronic disease, carbohydrate starvation, and in the fetus.
Where is thyroid hormone made? Is it stored? If so, how?
-Thyroid is made up of follicles
-These follicles have a ball of follicular cells on the outside and in the center of follicle is a mass of gunk, most of which is thyroglobulin. Thyroglobulin is a protein.

-Thyroid hormone is made in thyroglobulin.
-Then take thyroglobulin into the follicular cells, break it down to individual amino acids, and then release T3/T4
-Thyroglobulin can be thought of not only as the site of synthesis but also as the storage form of T3/T4
-lots of follicles in the thyroid therefore lots of thyroglobulin therefore sudden destruction of follicles releases tons of thyroid hormone
-control synthesis of thyroid hormone hormonally via TSH
-TSH is thyroid stimulating hormone and is made in the pituitary and it stimulates the follicular cells. Receptor for TSH is on the outside of these cells.
Describe the structure/function/location of TSH receptor
TSH receptor
-7 transmembrane domains
**g coupled receptor --> makes cAMP
-other effects on thyroid cells may be due to phospholipase A2 activation

-located on outside of thyroid follicular cells (basolateral membrane)
TSH increases the activity of
the iodide pump!!!
How do you take iodide from the circulation and get it into follicular cells?
1. Pump I- from blood stream into cell
-take Iodide, want to concentrate in the cell to use as a substrate for T3 production.
-We make a lot of T3 and T4, so we need a lot of iodide --> the higher the concentration the easier it is to synthesize
-Iodide pump on the basolateral membrane of the cell actively pumping --> gets energy from the sodium potassium ATP-ase. It’s hooked up to it, so iodide goes in with sodium.
-High concentration in the cell: can get up to 500:1 iodide inside: iodide outside if there is lots of TSH around
-Stimulate uptake by TSH.
-Can get some diffusion across the membrane, but because you normally pump it into the cell the diffusion is usually back out of the cell.

Remember, the overall process is:
-to get iodide from circulation inside and take it across the membrane
-iodide (I-) cannot get across the membrane very well on it’s own, so it need to be transported across the membrane
-we then have to add it to thyroglobulin, which is in the follicular space
-need to transport it across the cell to the follicular space membrane
-need to oxidize I
- to add it to thryoglobulin.
How can you inhibit the iodide pump?
-Iodide pump is NOT inhibited by PTU.
-what DOES block it --> thiocyanate prevents iodine from going into the pump and across the membrane. Thiocyanate not usually used technically, but it’s present in some foods, so if you eat enough of it can prevent iodide uptake and get hypothyroidsm
*note that thiocyanate competes with iodide but is NOT concentrated in the thyroid

-Other agents can protect pump from working: competitive inhibitors. Taken up by pump and concentrated in the cell:
a. perchlorate (ClO4-)
b. perrhenate (ReO4-)
c. pertechnetate (TcO4-)
-these drugs have the same partial specific volume as I'
-radioactive derivatives of these inhibitors, esp pertechnetate, can be sued for radiographic imaging of the thyroid. Perchlorate has been used to treat hypothryoidism.

NOTE: you can also inhibit the Na+/K+ pump with ouabain, thus inhibiting the iodide pump
Animals chronically stimulated with TSH have a T:S ratio of about __. Hypophysectomized animals have a T:S ratio of about __.
Animals chronically stimulated with TSH have a T:S ratio of about 500. hypophysectomized animals have a T:S ratio of about 5.
How does iodide cross the apical membrane and get into the follicular lumen?
Since the follicular lumen has the same electrochemical characteristics as the exterior of the cell, iodide rapidly travels down the electrochemical gradient to and across the apical membrane and into the lumen.
Where do the reactions with thryoglobulin occur?
-Brought it in want to add it to tyrosine.
-IMPORTANT: NOT adding it to tyrosine in the cytoplasm
-Need tyrosine to make thyroglobulin, which is present in the FOLLICULAR SPACE., on the luminal surface.
-Made thyroglobulin in the cell in the RER, then went through golgi, secretory pathway, and now it’s in the follicular space.

-Need to get I- across membrane at the top, need to oxidize it, and then couple it to the thyroglobulin present in the follicular space

-the reactions do NOT occur on the membrane. They occur in the follicular space.
What does PTU inhibit?
*PTU does NOT inhibit follicular iodide pump

PTU --> Inhibits everything BUT the pump.
INHIBITS: Thyroperoxidase, breakdown of thyroid hormone, the deiodinases (prevents t4 --> t3 conversion)
How do we oxidize iodide?
-Make H2O2 using peroxidase (an NADPH dependent enzyme resembling cytochrome C reductase)
-Add the iodide to thyroglobulin
-Oxidation/coupling process is complicated and may occur in multiple ways. People don’t know the actual molecular mechanism.
-Just remember that its gets oxidized and then added.

-ENZYME: thyroperoxidase
-->thyroperoxidase takes iodide and adds it to thryoglobulin.
-->TPO is a heme containing glycosylated enzyme that has an absolute requirement for H2O2.

Remember that the overall process is:
-to get iodide from circulation inside and take it across the membrane
-iodide (I-) cannot get across the membrane very well on it’s own, so it need to be transported across the membrane
-we then have to add it to thyroglobulin, which is in the follicular space
-need to transport it across the cell to the follicular space membrane
-need to oxidize I- to add it to thryoglobulin.
Where (glands) does iodide oxidation take place?
Iodide oxidation can only take place in the thyroid (other tissues such as the salivary glands, mammary gland, chorion, and stomach can take up and concentrate iodide but cannot oxidize it.
Organification
-the process of fixing iodine
-iodination of tyrosine residues on luminal thyroglobulin yields 3-monoiodotryosine (MIT) which is then iodinated at the 5 position to give 3,5-diiodotyrosine (DIT). This is catalyzed by thyroperoxidase.
-Free tyrosine can be iodinated to MIT but cannot be incorporated into the polypeptide chain of a protein since a tRNA does not recognize it.
Thyroperoxidase functions
1. Iodide oxidation (requires H2O2)

2. Iodination of tyrosine

3. Coupling of Iodotyrosils
Structure of thyroglobulin
-a homodimer of MW 660,000 with 8-10% carbohydrate, 0.2-1% iodide, 5496 amino acids (2748/polypeptide)
-on average, the thyroglobulin dimer contains 134 tyrosine residues, 5 MIT, 4.5 DIT, 2.5 T4, 0.7 T3.
-This predicts that 3,435 ATPs are required per molecule of T3 or T4 (2 ATPs are needed for each peptide bond); this does not take into account any other energy costs
Does the thyroid store any thyroid hormone? If so, where?
-Many weeks supply of hormone stored in the extracellular colloid
How do we add iodine to tyrosine?
ORGANIFICATION

--iodination of tyrosine residues on luminal thyroglobulin yields 3-monoiodotryosine (MIT) which is then iodinated at the 5 position to give 3,5-diiodotyrosine (DIT). This is catalyzed by thyroperoxidase.
-Free tyrosine can be iodinated to MIT but cannot be incorporated into the polypeptide chain of a protein since a tRNA does not recognize it.

-Take iodine and add to tyrosine to make MIT or DIT
-note mono and di – iodotryosine in image
*ring structure is numbered --> 3 and 5 are on either side of the -OH group on tyrosine
*Because it’s a ring structure, there is NO difference between 3 and 5 position
-As soon as you add an Iodine, it becomes a 3 by definition and you have now defined the 5 position. Means mono does not have an I on the 5 position.
How does coupling of iodotyrosils work?
Make DIT now 3 and 5 are going to have iodine.. can take MIT and DIT and fuse with thyroperoxidase and you get T3. this is NOT free tyrosine, it is part of the AA backbone of thyroglobulin. can do the same with two DITs and get T4. Most of what is in the thyroid is T4, a very small amount is T3. You can make it, but normally it’s not very much.

-Coupling of iodotyrosils in the thyroglobulin yields:
1. MIT + DIT = triiodothyronine (T3)
2. DIT + DIT = tetraiodothyronine (T4)

-this is bound to thyroglobulin
-the coupling reaction does not cleave the peptide bond -- it leaves behind dehydroalanine
-the direct addition of MIT or DIT to an iodotyrosine has not been ruled out

-This is catalyzed by thyroperoxidase and inhibited by thiourea drugs such as propylthiouracil (PTU)
How are T3 and T4 released?
-stimulated by TSH due to activation of adenylate cyclase

-occurs by the complete hydrolysis of thyroglobulin

-thyroglobulin is engulfed by phagocytosis, these vesicles then fuse with lysosomes to give secondary lysosomes (phagolysosomes)

-breaks down amino acids to go back to be used for thyroglobulin again.

-hydrolysis of thyroglobulin in the secondary lysosomes yields the iodinated amino acid derivative T3, T4, DIT, and MIT.

-There is some specific deiodination of T4 to T3, however most deiodination of T4 occurs in the periphery. T3 and T4 are released from the cell.


-NOTE: DIT and MIT are not released. They are reused:
a. DIT and MIT are deiodinated by a deiodinase, which requires NADPH, to make tyrosine and the products are recycled (**no tRNA that recognized MIT/DIT so they cant be incorporated directly)

-30% of dietary iodide is absorbed ie. about 150 ug required for the average daily synthesis of T4 and T3 containing 50 ug iodide
What happens if you have excess levels of iodide?
-counterintuitively, increased iodide can inhibit T3 and T4 production

-iodide treatment is often used clinically to prevent thyroid storm

-multiple, poorly understood mechanisms are involved
Short term effects of excess levels of iodide
Wolfe-Chaikoff Effect

-transient block in organification due to high intracellular levels of iodide

-relieved after 48 hours due to increased export of iodide
Medium term effects of excess levels of iodide
-increased organification leading to increased MIT and DIT but decreased T3/T4

-Decreased release of T3/T4 possibly due to decreased T3/T4 content of thyroglobulin

-Cells recover after 7-10 days
Long term effects: of excess levels of iodide
-In unusual cases, the iodide block becomes permanent and a goiter and hypothyroidism develop
-These events are probably due to some underlying defect in the thyroid
-The mechanism of recovery from iodide inhibition may involve
iodinated arachidonic acid
Wolfe-Chaikoff Effect
Short term effects of excess levels of iodide
Why do we care about the half life of T3 and T4?
-T3 and T4 will do same thing, but because they last different times in circulation, doses are different
-T3 has ½ life of 1.5 days. Need to take T3 multiple times a day. Many patients don’t like this, it’s hard to keep up with that regimen.
-T4 can be given once a day, keep an even dose this way.
-Some patients seem to prefer t3 to t4 (feel better on T3 than T4 even though their TSH levels are normal)

also keep in mind the halflife when taking patients off of T3/T4 for diagnostic testing
Best way of looking at thyroid hormone in the patient?
-Normal way of measuring T3 and T4 levels in the patient:
-You can do T3 or T4 assays, but the most sensitive way is to ask how much TSH there is -
TSH is the regulator: do assay for TSH to see if you’re producing a lot of TSH (meaning you’re hypothyroid, don’t have enough thyroid hormone) or you’re low TSH (means your hyperthyroid have high thyroid hormone levels and you’re turning off) Patient where you have to take off thyroid hormone to do diagnostic test

-The liver synthesizes TBG, estrogen increases TBG while androgens and glucocoritcoids decrease TBG. Steroids increase the liver’s synthesis of TBG.
-if you’re on birth control or some other medications, your TBG (carrier protein) is higher than it was before you started birth control
-Does not mean you’re hypo or hyperthyroid, you’re EUTHYROID --> normal thyroid levels. Doesn’t matter how much TBG you make.
-If you’re a physician and you’re measuring thyroid hormone levels, when you’re looking at T4 for instance, 0.03 percent is free rest is bound. If you do a T4 assay on that patient asking if patient has normal T4, most of what you’re measuring is bound T4, which is inactive. If that patient is doing something to change their TBG levels, you’ll get an abnormal result --> Meaningless.

**Best assay --> TSH OR free T3 or free T4 assays (theoretically the T3 and T4 assays are not as good )
How do you transition a patient off T3/T4?
Taking patient off T3 or T4 to do some diagnostic test
-want to find out if their condition is resolved, for instance.
-If you have them on T4, have to wait weeks for what you’ve been giving them goes away.
-If you have them on T3 you can wait a week or a few days
-If you know you’re going to need to take them off it in the future, can take the patient off T4, put on T3 for a while, and then remove T3 to do the diagnostic assay
-If you can’t make T3 or T4 and medication is removed patient feels terrible, can hardly be able to function whatsoever. Putting them on T3 makes this easier.
When might you be taking a patient off T3/T4?
-common practice taking people off T3 and T4 with thyroid cancer
-In thyroid cancer typically remove the thyroid and give replacement T4
-BUT concerned about recurrence, so you want to scan for cancer using radioactive iodine
-If cells have metastasized, take up iodine again, look for radioactivity
-by taking off T3 and T4 again makes TSH high, stimulating cancer cells to take up iodine
-this is a common test, but not as common in industrial countries anymore since we have recombinant TSH. Can give patient TSH directly and they’ll take up iodine.
-Even in america, going back to the radioactive method has increased since there has been a shortage in TSH, difficulty making TSH.
How is T3 and T4 transported?
-Over 99% of T3 and T4 are bound to the carrier proteins
-thyroxine-binding globulin (TBG) (~70%), thyroxine-binding prealbumin (TBPA) (10-15%), and albumin (~15-20%)

-TBG has 100x the affinity for T3 and T4 compared with TBPA

-Plasma t1/2 of T3 is 1.5 days, of T4 is 6.5 days

-For clinical purposes it is important to measure free as well as total hormone levels since many agents alter TBG levels and thus total hormone without altering free hormone levels
What competes for binding to TBG with T3 and T4?
-Phenytoin and salicylates compete for binding to TBG.
T4 --> T3
Conversion of T4 to T3

-occurs mainly in the periphery
-ENZYME: thyroxine deiodinase converts T4 to T3 and to reverse T3 (rT3)
-T3 has a 10x higher affinity for the thyroid hormone receptor than T4, i.e. T3 is the most physiologically important thyroid hormone
-rT3 binds to the receptor very weakly – its function, if any, is not known. Large amounts are made during chronic disease, carbohydrate starvation, and in the fetus.
-PTU inhibits this conversion
Thiourea class of drugs
What is the drug of choice to inhibit the formation of thyroid hormone?

When might you use a different drug?
Methimazole is the drug of choice.

PTU --> Inhibits everything BUT the pump.
INHIBITS: Thyroperoxidase, breakdown of thyroid hormone, the deiodinases (prevents t4 --> t3 conversion)

BUT

it has severe side effects (black box warning) --> can be severe complications, get severe liver damage/failure which is life threatening.

-PTU only used during certain circumstances:
a. 1st trimester (methimazole gives birth defects)
b. With thyroid storm (PTU is preferred because methimazole does not block T4 -->T3 conversion).
B. Some people are allergic to drugs, if you’re allergic to methimazole then give PTU
How do you regulate thyroid hormone synthesis?
Pituitary and hypothalamus

- hypothalamus makes TRH, TRH stimulates pituitary to produce TSH. TSH goes to thyroid and turns on TH synthesis through action on the TSH receptor. There is feedback of TH in the hypothalamus and the pituitary

-One complication: somatostatin also controls TSH activity
-Somatostain turns off growth hormone production in the pituitary which normally turns on IGF1 production in the liver, which feeds back to the hypothalamus to turn on somatostatin
What might you need to be concerned about if you’re treating a patient with GH?
If you’re treating a patient with GH, you have high GH levels, you get high IGF-1, increases production of somatostatin, which turns OFF endogenous GH and TSH activity. Thus, if you’re treating patients with GH, or if you’re an athlete taking GH, you can make yourself/patient hypothryoid

-high percentage of patients taking GH become hypothyroid and need TH supplementation.
What does T3 inhibit?
-T3 inhibits thyroid stimulating hormone (TSH) from the pituitary
-T3 probably inhibits thyrotropin releasing hormone (TRH) synthesis and release from the hypothalamus
-Conversely low T3 levels stimulate TRH release
-TRH stimulates TSH release
Thyroid hormone receptor genes
-two genes encode the thyroid hormone receptors, Tra and TRb
-the two receptors are expressed differentially both in different tissues and during development
-There are two TRb splice variants, TRb1 and TRb2; both are active receptors with differential expression
-There are two major splice variants of Tra, TRa1 and TRa2. These splice variants do not bind hormone and their function is unknown.
-Hormone binding domain ~27,000 daltons
-DNA binding domain ~10,000 daltons (2 zinc coordinated cysteine fingers)
-member of the retinoid/thyroid/steroid hormone superfamily of receptors
-most active form is a heterodimer of RXR and TR
Tell me about T3 and its interactions with TR
-T3 is usually the active hormone since it binds 10x better to the TR than T4
-The TR is a nuclear receptor in both the absence and presence of hormone
-TR is bound to specific DNA sequences termed thyroid response elements (TRE) whether hormone is present or not
-In the absence of hormone the TR represses transcription
-in the presence of hormone the receptor activates transcription by recruiting transcriptional coactivators that interact with the initiation complex
-TR can bind to DNA either as a homodimer or as a heterodimer with RXR
-The RXR-TR heterodimer is usually most active
When it binds to inverted repeats, expect it to bind as a ___.
Direct repeats bind as ____.
When it binds to inverted repeats, expect it to bind as a homodimer.

Direct repeats bind homodimer or heterodimer.
TREs
thyroid hormone response elements

-TR binds to a TRE mainly as a heterodimer wit hRXR.
-TREs consist of inverted (palindromic) or direct repeats of the consensus sequence AGGTCA
-when present as direct repeats, the repeats are usually separated by 4 base pairs.
-TREs are found in the growth hormone gene. This explains the effects of thyroid hormone on growth
-TREs are found in the cardiac sarcoplasmic reticulum Ca2+
-ATPase gene SERCA2. SERCA2 controls the uptake of Ca2+ into the endoplasmic reticulum, a rate-limiting event in muscle contraction. That is, T3 increases SERVA2 and thus heart rate.
-T3 also increases heart rate by increasing the transcription of specific isoforms of myosin. Again, these genes contain TREs.
Why might you not have enough iodine in your diet?
-If you live by sea, eat lots of fish, shellfish, seaweed, you’d get a lot of iodide in your diet.
-If you’re living inland in the middle of a continent, then you’re unlikely to be eating fish from the sea under normal circumstances, might not get enough iodine, get hypothyroidism and get goiter.
-Mountainous regions also tend to be low in iodine.
-In America, salt is normally iodized so we get high levels of iodine.
Goitrogens
substances that suppress the function of the thyroid gland by interfering with iodine uptake, which can, as a result, cause an enlargement of the thyroid, i.e., a goitre.
Endemic Goiter
Endemic goiter
-Insufficient dietary intake of iodine leading to insufficient production of TH and thus constitutive production of TSH.
-not enough iodine don’t make enough thyroid hormone. SO you make TSH and high levels of TSH have two effects:
1. tries to make your thyroid make more thyroid hormone
-->Most of hormones from pituitary are hypertropic (try to get you to grow)
-->Thus, it tries to make your thyroid grow even if it cannot make enough thyroid hormone. Gets bigger and gives you a goiter.

Can get goiter if you have thyroid hormone deficiency OR if you ingest certain foods that have a goitrogen in them. Eg. thiocyanate. Get low iodide + goitrogen, get dramatic effects.
Congenital hypothryoidism:
-Insufficient TH production due to a malfunctioning thyroid

-TH treatment at birth prevents cretinism

--relatively high % of babies have congenital hypothyroidism
-all babies in this country tested for TH soon after birth
-can give TH if their levels are low and they develop normally.
-TH is extremely important for developmental processes, especially how the brain develops
-somatostatin feedback is also extremely important for growth. If we don’t have enough TH we’re short. And because brain is not developing properly have a very low IQ.

on LEFT is someone from Zaire:

-in Zaire, especially in the countryside, there are low levels of iodine in diet
-main dietary ingredients is cassava (fine in small amounts .. Tapioca is made from cassava, but it contains thiocyanate which inhibits thyroid hormone production)
-have thiocyanate + low iodine diet --> gives population a high chance of having a goiter (on right) OR cretinism (on left)

CRETINISM:
-low levels of TH from birth
-large stomachs
-very short
in this population in Zaire, some of the population looked like person on left and on one right and variants in between in some cases TSH could get the thyroid to produce enough TH so that they were subclinically hypothyroid – that is, they were really hypothyroid but they’re functioning pretty normally. But TSH is high they get a goiter. In other cases they don’t have enough thyroid hormone during development, become very hypothyroid, and they get cretinism.
Can you treat cretinism after is has developed?
-Can treat this but only if you give thyroid hormone at birth
-cannot treat cretinism after it has developed
ie. once you’re short, have low IQ after 1st year or so not much you can do

on left typical baby with no thyroid hormone: dull eyes turned down mouth
Baby on right has been given thyroid hormone
Graves disease
(autoimmune)

-Production of antibodies against the TSH receptor (TSI-thyroid stimulating immunoglobulin)
-Grave’s disease is due to receptor-activating autoimmune antibodies against the TSH receptor
-Chronic stimulation of the TSH receptor
-Unregulated TH production
-Because you have an antibody turning on thyroid hormone , not TSH, have no feedback (cant turn down immunoglobulin). Lose all control of TH production. TH is high, patients with this kind of disease have a goiter (have goiter when your hypo or hyper thyroid)
-Diffuse goiter, (not big and nodular), hyperthyroidism.
-70% of patients also have Hashimoto's.
-Treatment can include I131, PTU, surgery.
-very well known people have had it (e.g. Barbara Bush)
-main effect of Graves disease are eyes that stick out, don’t close eyelids.
-women have higher incidence of autoimmune disease than males
-Grave’s disease is due to
receptor-activating autoimmune antibodies against the TSH receptor
What is the most common form of hyperthyroidism?
-Grave’s disease is the most common form of hyperthyroidism
How do you treat Graves disease??
A. Can treat by removing some of the thyroid --> surgery

B. Can also give radioactive iodine (before talked about it to scan to see where iodine was taken up) now use strong form, high does, destroy the thyroid (gets concentrated there and thyroid gets obliterated by radioactivity) --> I131
*note: this typically causes patient to become hypothyroid and require thyroid hormone replacement

C. PTU
Why are patients eyes affected with graves disease?
- Get immune reaction behind the eye, not due directly to thyroid hormone but due to antibody against TSH receptor interacting with cells behind eye causing inflammation
-that process causes the eye to be pushed out of its socket and that’s why you get this kind of effect
-also get muscle damage. As soon as you get muscle damage in the eye you can’t turn eye in one way or the other (eg. example E)
-can also get infections because your tears protect your eyes, keep them moist and wash away debris and bacteria. But as soon as eye gets pushed out, eyelids don’t get bigger, have difficulty covering eyeball
-In extreme cases can’t close your eyelids. If you can’t cover the eye if it gets too big and then the eye dries out and it has to be removed
How do we treat Graves?
-Get rid of excess thyroid hormone, can get rid of thyroid, but still have immunoglobulin
-->how do you treat this (or say they don't want/can't have surgery)?
can treat with methimazole

-Can have surgery --> may give some remission of effects (less stimulation of immune system), but you don’t totally wipe out the effects.
Hashimoto’s Thyroditis
-autoimmune
-Production of antibodies against thyroperoxidase & thyroglobulin. Slow destruction of the thyroid leading to hypothyroidism.

-In initial stages may be hyperthyroid because you suddenly start releasing stored hormone, but long term effect is hypothyroidism.

** notice: 70% of patients with graves also have Hashimoto’s. They have autoimmune disease, antibody against the thyroid.
**They’re likely to make more than one antibody against it
-If they produce mainly Ab against TSR, they have Grave’s disease
-OR more likely, have mixture of antibody --> Grave’s patients have Ab against TSR but also against thyroglobulin and thyroperoxidase.
-Get destruction of the thyroid and activation of thyroid at same time
-Clinical phenotype depends on which dominates: destruction or activation
Iodine

high v. low levels
-Low levels can stimulate TH synthesis

-High levels cause a transient block in organification due to the Wolff-Chiakoff effect.
-->eg. protect against nuclear power plant and also from thyroid storm during surgery!

-With underlying Hashimoto's may lead to goiter and hypothyroidism (long term blockage with high dose bolus)
How can you protect yourself from radioactivity from power plant?
-one way to protect yourself from radioactivity from power plant is to take iodine tablets.

-Dose yourself up with iodine prevent uptake of radioactive iodine following nuclear explosion, prevent thyroid tumors

-high iodine diet can also stimulate TH production

-moderate increase stimulates TH production, esp if you’re slightly hypothyroid

-large amounts turn off TH or prevent radioactive iodine uptake; in some cases prevent thyroid hormone production

-give large does of iodine transiently prevent TH production
What might you need to be concerned about if you're doing a surgery around the thyroid? What should you do preemptively?
Patient going for neck surgery in/around the thyroid

- when you start playing with someone’s thyroid you get a response: breakdown of the thyroid
- Get release of thyroglobulin, T3/T4 release.
-During surgery, you can all of a sudden have a patient whose thyroid hormone level has spiked.
-Thyroid hormone increases HEART RATE.
-To prevent thyroid storm, can give high dose of normal iodine.
- In most people, you can get transient block not as much released prevent thyroid storm (but in people w/ underlying Hashimoto's, can have long term block --> goiter and hypothyroidism)
How does lithium affect the thyroid?
-lithium prevents thyroid hormone release
-25% of patients taking lithium have a goiter and hypothyroid
-this image is a newborn that died of asphyxiation after birth
-this kid died not because he had thyroid problem per se but because the mom was taking a cough medication which contained iodine.
-the mother didn’t realize she was taking a high level of iodine in pregnancy which caused the Wolff-Chiakoff effect which in this case became a long term effect in her child.
-Note the large goiter that choked off the airways
Biological effects of thyroid hormone; are they universal?
-Thyroid hormone increases oxygen consumption. May be due to the known TH effect of increasing the number of Na+/K+ ATPase molecules since it has been suggested that this pump is the major energy drain in most cells
-TH enhances general protein synthesis giving a positive nitrogen balance
-Amphibian metamorphosis (tadpole to frog) is dependent on TH
-TH is required for normal human growth and development. Lack of TH postnatally results in cretinism. TH replacement therapy at birth allows normal development

-Thyroid hormone has huge developmental effects
-also affects metabolic rate does it in all animals that use TH for regulation?
-Frogs use TH. Frogs don’t go from tadpoles --> frogs w/o sufficient thyroid hormones
-Tadpoles given exogenous TH develop faster.
- Xenopus grown in PTU for many months on left, should have developed into a frog a long time ago. BUT it stays at this stage, has rear legs just starting to emerge; it’s eyes are still on the outside looking sideways. Its skin is still very thin (can see vasculature, nerves). Still swims using its tale.
-Short time after T3 is added to water bath, it turns into a frog!!! The tail starts disintegrating, the front and back legs develop, the eyes change, way it excretes nitrogen changes.
-Thyroid hormones changes development in many animals. BUT in terms of metabolic rates/metabolism, that depends. Only birds and mammals are controlled by TH --> heat generation!
High thyroid horomone high metabolic rate high energy production -->HEAT GENERATION.

This is why hyperthyroid (graves) you feel hot, want to be in cold

Not true in frogs, insects, naked mole rat (a mammal)
gynandromorph
eg. Birds
-developed where one side of body is genetically male the other side of the body is genetically female
-all the hormones they produce are circulating on both sides. Male and female cells on either side but hormone levels the same on either side.

-this notion that endocrines control everything, you are what your hormones are doing to you --> not quite the case


Chicken :
-on left, female side has small chest; male side has big chest
-right is male this side has testis
-female side has ovary
-circulating hormones are the SAME
-this chicken looks male or female NOT due to circulating hormones
(this is not true for us in the audience --> give androgens to people, they start to look male)
Symptoms of hyperthyroidism include
proptosis, heat intolerance, tremor, weight loss
Symptoms of hypothyroidism include
cold intolerance, weight gain, cold clammy skin