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How is T3 produced?
Hi. I am a 39-year-old male, and I have hypothyroidism. I've posted to this forum before.
I had some blood tests in early March 2013, and the results were as follows:
TSH = 0.446 (normal range = 0.450 - 4.500 uIU/mL)
Total T4 = 9.9 (normal range = 4.5 - 12.0 ug/dL)
FT4 = 1.41 (normal range = 0.82 - 1.77 ng/dL)
Total T3 = 106 (normal range = 71 - 180 ng/dL)
FT3 = 3.0 (normal range = 2.0 - 4.4 pg/mL)
My endo believes that the Total T4 and Total T3 tests provide a "more complete" picture, and that's why she orders these tests.
Now, my understanding was that all T3 (bound and unbound) is produced from Free T4. Well, you can see that my Free T4 is 1.41 ng/dL, and that my Total T3 (bound and unbound) is 106 ng/dL. Obviously, the amount of Total T3 is far greater than the amount of Free T4. So, is all T3 (bound and unbound) produced from Free T4? Or is there another source of T3?
Thank you for any info.
I had some blood tests in early March 2013, and the results were as follows:
TSH = 0.446 (normal range = 0.450 - 4.500 uIU/mL)
Total T4 = 9.9 (normal range = 4.5 - 12.0 ug/dL)
FT4 = 1.41 (normal range = 0.82 - 1.77 ng/dL)
Total T3 = 106 (normal range = 71 - 180 ng/dL)
FT3 = 3.0 (normal range = 2.0 - 4.4 pg/mL)
My endo believes that the Total T4 and Total T3 tests provide a "more complete" picture, and that's why she orders these tests.
Now, my understanding was that all T3 (bound and unbound) is produced from Free T4. Well, you can see that my Free T4 is 1.41 ng/dL, and that my Total T3 (bound and unbound) is 106 ng/dL. Obviously, the amount of Total T3 is far greater than the amount of Free T4. So, is all T3 (bound and unbound) produced from Free T4? Or is there another source of T3?
Thank you for any info.
There are actually two sources. The thyroid gland produces and releases into the blood, thyroid hormone in a ratio that is approximately 20 to one, T4 to T3. Then as you mentioned, the body also converts T4 to T3.
Your doctor believes that Total T4 and Total T3 tests provide a more complete picture. I have seen an argument that said that Total T4 was important because that tells whether there is even enough thyroid hormone to work with. Further, that Free T4 can be artificially elevated from certain drugs so it is important to know the total T4 to get an accurate picture of thyroid levels. So that is probably what the doctor has in mind.
Total T3, on the other hand, does not seem to be important to know. But if both tests make your doctor happy, and the doctor is willing to always test for the Frees, then why worry? You are way ahead of so many hypo patients that have doctors that only want to test for TSH, and sometimes Free T4.
Your doctor believes that Total T4 and Total T3 tests provide a more complete picture. I have seen an argument that said that Total T4 was important because that tells whether there is even enough thyroid hormone to work with. Further, that Free T4 can be artificially elevated from certain drugs so it is important to know the total T4 to get an accurate picture of thyroid levels. So that is probably what the doctor has in mind.
Total T3, on the other hand, does not seem to be important to know. But if both tests make your doctor happy, and the doctor is willing to always test for the Frees, then why worry? You are way ahead of so many hypo patients that have doctors that only want to test for TSH, and sometimes Free T4.
T4 is 4 iodine molecules around a ring of tyrosine. Enzymes called deiodinases (dependent on selenium) converts T4 to T3 by removing an iodine atom from the outer tyrosine ring. T3 - 3 iodine molecules around a ring of tyrosine. T4 also converts to reverse T3 (rT3) by removing an inner ring iodine atom.
Given the blood-test results that I mentioned in my first post, I believe that I may have a problem with "FT4-to-FT3 conversion".
My Total T4 is above the middle of the Total T4 normal range, and my FT4 is above the middle of the FT4 normal range. People on this forum have said that the FT4 should be in the middle of the FT4 normal range. If the same holds for Total T4, then both my Total T4 level and my FT4 level are good.
However, people on this forum have also said that the FT3 should be in the upper one-third of the FT3 normal range, and my FT3 is below the middle of the FT3 normal range.
This suggests to me that not enough FT4 is being converted to FT3.
When I had these blood tests, I was also tested for Vitamin E, Selenium, and Zinc. Deficiencies in these substances could interfere with "FT4-to-FT3" conversion. Since Zinc is connected to Copper, and since Copper is connected to Iron, I was tested for Copper and Iron (Ferritin) as well.
Too much or too little Cortisol also can interfere with "FT4-to-FT3" conversion. I was tested for Cortisol, too.
The results were as follows:
vitamin E (Alpha Tocopherol) (serum) = 7.8 (normal range = 4.6 - 17.8 mg/L)
Selenium (plasma or serum) = 161 (normal range = 79 - 326 ug/L) (detection limit = 10 ug/L)
Zinc (plasma or serum) = 90 (normal range = 56 - 134 ug/dL) (detection limit = 5 ug/dL)
Copper (plasma or serum) = 114 (normal range = 72 - 166 ug/dL) (detection limit = 5 ug/dL)
Ferritin (serum) = 276 (normal range = 30 - 400 ng/mL)
Cortisol - AM = 18.1 (normal range = 6.2 - 19.4 ug/dL)
Note: I had the Cortisol test done at my "morning awakening". Because I usually went to bed late and woke up late, my "morning awakening" was about 1:15 PM. The Cortisol test, and the ten other blood tests mentioned above, were all done with the same blood draw.
Well, the Zinc is just a little below the middle of the Zinc normal range, and the Copper is just a little below the middle of the Copper normal range. The Ferritin is in the upper one-third of the Ferritin normal range. So, the Zinc, Copper, and Ferritin levels seem to be correct.
My Cortisol level seems to be in the very high normal range. Could my Cortisol level be *too* high? Could my Cortisol level be causing "FT4-to-FT3 conversion" problems?
Now we come to the Selenium and the Vitamin E. My Selenium level is in the lower one-third of the Selenium normal range, and my Vitamin E level is in the lower one-fourth of the Vitamin E normal range. So, it seems to me that my Selenium and Vitamin E levels are too low. It seems that these low levels are the most likely cause of "FT4-to-FT3 conversion" problems.
So, do you guys think I have problems with FT4-to-FT3 conversion? If yes, do you think that deficiencies in Selenium and/or Vitamin E are to blame?
I have two additional questions. I have read that most FT4-to-FT3 conversion occurs inside a cell, NOT in the blood. Thus, it appears that measuring the amount of FT3 in the blood is giving us an incomplete picture of just how much FT3 we have in our bodies. So, why do we rely on the FT3 blood test so much? And is there a way to determine how much FT3 there is inside a cell?
My Total T4 is above the middle of the Total T4 normal range, and my FT4 is above the middle of the FT4 normal range. People on this forum have said that the FT4 should be in the middle of the FT4 normal range. If the same holds for Total T4, then both my Total T4 level and my FT4 level are good.
However, people on this forum have also said that the FT3 should be in the upper one-third of the FT3 normal range, and my FT3 is below the middle of the FT3 normal range.
This suggests to me that not enough FT4 is being converted to FT3.
When I had these blood tests, I was also tested for Vitamin E, Selenium, and Zinc. Deficiencies in these substances could interfere with "FT4-to-FT3" conversion. Since Zinc is connected to Copper, and since Copper is connected to Iron, I was tested for Copper and Iron (Ferritin) as well.
Too much or too little Cortisol also can interfere with "FT4-to-FT3" conversion. I was tested for Cortisol, too.
The results were as follows:
vitamin E (Alpha Tocopherol) (serum) = 7.8 (normal range = 4.6 - 17.8 mg/L)
Selenium (plasma or serum) = 161 (normal range = 79 - 326 ug/L) (detection limit = 10 ug/L)
Zinc (plasma or serum) = 90 (normal range = 56 - 134 ug/dL) (detection limit = 5 ug/dL)
Copper (plasma or serum) = 114 (normal range = 72 - 166 ug/dL) (detection limit = 5 ug/dL)
Ferritin (serum) = 276 (normal range = 30 - 400 ng/mL)
Cortisol - AM = 18.1 (normal range = 6.2 - 19.4 ug/dL)
Note: I had the Cortisol test done at my "morning awakening". Because I usually went to bed late and woke up late, my "morning awakening" was about 1:15 PM. The Cortisol test, and the ten other blood tests mentioned above, were all done with the same blood draw.
Well, the Zinc is just a little below the middle of the Zinc normal range, and the Copper is just a little below the middle of the Copper normal range. The Ferritin is in the upper one-third of the Ferritin normal range. So, the Zinc, Copper, and Ferritin levels seem to be correct.
My Cortisol level seems to be in the very high normal range. Could my Cortisol level be *too* high? Could my Cortisol level be causing "FT4-to-FT3 conversion" problems?
Now we come to the Selenium and the Vitamin E. My Selenium level is in the lower one-third of the Selenium normal range, and my Vitamin E level is in the lower one-fourth of the Vitamin E normal range. So, it seems to me that my Selenium and Vitamin E levels are too low. It seems that these low levels are the most likely cause of "FT4-to-FT3 conversion" problems.
So, do you guys think I have problems with FT4-to-FT3 conversion? If yes, do you think that deficiencies in Selenium and/or Vitamin E are to blame?
I have two additional questions. I have read that most FT4-to-FT3 conversion occurs inside a cell, NOT in the blood. Thus, it appears that measuring the amount of FT3 in the blood is giving us an incomplete picture of just how much FT3 we have in our bodies. So, why do we rely on the FT3 blood test so much? And is there a way to determine how much FT3 there is inside a cell?
Free T3 is just that. It's what is freely floating around in our blood, available for cells to use.
How much our cells decide to use, is always in question.
How much our cells decide to use, is always in question.
When you started this thread, you asked some specific questions taht we tried to answer satisfactorily. Now it seems we are getting into trying to diagnose your status and possible causes. So, we need to get into much more information from you.
To start, what symptoms do you have? What thyroid meds/other supplements are you taking and in what dosages?
To start, what symptoms do you have? What thyroid meds/other supplements are you taking and in what dosages?
T4 is converted into T3 by the deiodinase system (D1, D2, D3) in multiple tissues and organs but especially in the liver (this is where most of the conversion occurs), kidney, gut, skeletal muscle, brain, thyroid gland. I have read that tissues expressing D2 will have an additional source of T3 contributed by intracellular T4 to T3 conversion.
"Plasma or serum zinc levels are the most commonly used indices for evaluating zinc deficiency, but these levels do not necessarily reflect cellular zinc status due to tight homeostatic control mechanisms [8]. Clinical effects of zinc deficiency can be present in the absence of abnormal laboratory indices [8]." - National Institutes Of Health.
Another test for zinc is the zinc sulfate taste test. I go into more detail on another answer of mine on the link below. I didn't realise this at the time but my poor appetite (besides poor appetite due to hypothyroidism) is a zinc deficiency symptom (appetite isn't that great even when very hyperthyroid).
http://www.medhelp.org/posts/Vitamins--Supplements/zinc-deficeincy-question/show/1669131
I had dramatic results after three days of eating a few brazil a day (one nut contains something like 50 to 90mcg of selenium). Clearly i was deficient (*rolls eyes* - i'm always deficient in something lol). Try eating a few brazil nuts a day and see how you feel.
Lab tests are a guide at best...
"The problem lies in the fact that the exact amount of thyroid hormones entering the cells is impossible to determine with a laboratory test. And there is no exact way to measure what takes place inside the billions of cells, where thyroid hormone controls the rate of metabolism." - Excerpt from the book "Cracking The Metabolic Code - The 9 Keys to Peak Health" By James B. LaValle, Stacy Lundin Yal.
"Plasma or serum zinc levels are the most commonly used indices for evaluating zinc deficiency, but these levels do not necessarily reflect cellular zinc status due to tight homeostatic control mechanisms [8]. Clinical effects of zinc deficiency can be present in the absence of abnormal laboratory indices [8]." - National Institutes Of Health.
Another test for zinc is the zinc sulfate taste test. I go into more detail on another answer of mine on the link below. I didn't realise this at the time but my poor appetite (besides poor appetite due to hypothyroidism) is a zinc deficiency symptom (appetite isn't that great even when very hyperthyroid).
http://www.medhelp.org/posts/Vitamins--Supplements/zinc-deficeincy-question/show/1669131
I had dramatic results after three days of eating a few brazil a day (one nut contains something like 50 to 90mcg of selenium). Clearly i was deficient (*rolls eyes* - i'm always deficient in something lol). Try eating a few brazil nuts a day and see how you feel.
Lab tests are a guide at best...
"The problem lies in the fact that the exact amount of thyroid hormones entering the cells is impossible to determine with a laboratory test. And there is no exact way to measure what takes place inside the billions of cells, where thyroid hormone controls the rate of metabolism." - Excerpt from the book "Cracking The Metabolic Code - The 9 Keys to Peak Health" By James B. LaValle, Stacy Lundin Yal.
Since early November 2012, I have taken the following:
Synthroid, 137 mcg, 1 day per week
Synthroid, 125 mcg, 6 days per week
Vitamin B12, 1000 mcg, 3 days per week
As for symptoms, I have been experiencing the standard symtoms of hypothyroidism:
arthritic hands, pain in joints, sensitivity to cold, memory lapses
I asked about how T3 was produced because I was concerned about conversion issues.
Synthroid, 137 mcg, 1 day per week
Synthroid, 125 mcg, 6 days per week
Vitamin B12, 1000 mcg, 3 days per week
As for symptoms, I have been experiencing the standard symtoms of hypothyroidism:
arthritic hands, pain in joints, sensitivity to cold, memory lapses
I asked about how T3 was produced because I was concerned about conversion issues.
Red_Star wrote:
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I had dramatic results after three days of eating a few brazil a day (one nut contains something like 50 to 90mcg of selenium). Clearly i was deficient (*rolls eyes* - i'm always deficient in something lol). Try eating a few brazil nuts a day and see how you feel.
--------------
Unfortunately, I have a mild peanut allergy. Eating peanuts and/or nuts can cause me to have mild allergic reactions.
--------------
I had dramatic results after three days of eating a few brazil a day (one nut contains something like 50 to 90mcg of selenium). Clearly i was deficient (*rolls eyes* - i'm always deficient in something lol). Try eating a few brazil nuts a day and see how you feel.
--------------
Unfortunately, I have a mild peanut allergy. Eating peanuts and/or nuts can cause me to have mild allergic reactions.
There are many different suggestions about causes for poor conversion of T4 to T3. You have covered the most important ones, and I see nothing that stands out as a factor. Yet your Free T3 is below the middle of its range, which is too low to relieve symptoms for many hypo patients. The range is far too broad due to the way it was established. A functional range would be more like the upper half of the current range. That is why you hear so often that symptom relief required Free T3 in the upper third of its range and Free T4 around the middle of its range.
And remember that Free T3 is the most important because it largely regulates metabolism and many other body functions. Also, scientific studies have shown that Free T3 correlated best with hypo symptoms, while Free T4 and TSH did not correlate at all.
At this point it may be an academic discussion as to what is causing inadequate conversion. Why not just do what a good thyroid doctor does? A good thyroid doctor will treat a hypo patient clinically by testing and adjusting Free T3 and Free T4 as necessary to relieve symptoms, without being constrained by resultant TSH levels. You can get some good insight into clinical treatment from this letter written by a good thyroid doctor for patients that he sometimes consults with after initial tests and evaluation. The letter is then sent to the participating doctor of the patient to help guide treatment. In the letter, please note the statement, "the ultimate criterion for dose adjustment must always be the clinical response of the patient."
http://hormonerestoration.com/files/ThyroidPMD.pdf
Do you think your doctor will treat clinically as described? If not, then you may have to find a doctor that will do so.
In a prior post you also raised two questions. "I have two additional questions. I have read that most FT4-to-FT3 conversion occurs inside a cell, NOT in the blood. Thus, it appears that measuring the amount of FT3 in the blood is giving us an incomplete picture of just how much FT3 we have in our bodies. So, why do we rely on the FT3 blood test so much? And is there a way to determine how much FT3 there is inside a cell? "
Red_Star answered the first. For the second part, yes there can be a difference between serum and tissue thyroid levels. Doctors rely on serum levels because there are no direct measures of tissue thyroid levels. There are some tests that measure the direct effect of tissue thyroid levels on the metabolic processes in the cells, but they are largely ignored by doctors of today. These include basal temperature and metabolic rate measurements. When it becomes necessary there is a recommended way of assessing tissue thyroid levels by using the ratio of Free T3 to Reverse T3; however, this is of value mostly when serum test results don't seem to align with symptoms. If interested in more detail, this link is a good source.
http://nahypothyroidism.org/thyroid-hormone-transport/#treatment
And remember that Free T3 is the most important because it largely regulates metabolism and many other body functions. Also, scientific studies have shown that Free T3 correlated best with hypo symptoms, while Free T4 and TSH did not correlate at all.
At this point it may be an academic discussion as to what is causing inadequate conversion. Why not just do what a good thyroid doctor does? A good thyroid doctor will treat a hypo patient clinically by testing and adjusting Free T3 and Free T4 as necessary to relieve symptoms, without being constrained by resultant TSH levels. You can get some good insight into clinical treatment from this letter written by a good thyroid doctor for patients that he sometimes consults with after initial tests and evaluation. The letter is then sent to the participating doctor of the patient to help guide treatment. In the letter, please note the statement, "the ultimate criterion for dose adjustment must always be the clinical response of the patient."
http://hormonerestoration.com/files/ThyroidPMD.pdf
Do you think your doctor will treat clinically as described? If not, then you may have to find a doctor that will do so.
In a prior post you also raised two questions. "I have two additional questions. I have read that most FT4-to-FT3 conversion occurs inside a cell, NOT in the blood. Thus, it appears that measuring the amount of FT3 in the blood is giving us an incomplete picture of just how much FT3 we have in our bodies. So, why do we rely on the FT3 blood test so much? And is there a way to determine how much FT3 there is inside a cell? "
Red_Star answered the first. For the second part, yes there can be a difference between serum and tissue thyroid levels. Doctors rely on serum levels because there are no direct measures of tissue thyroid levels. There are some tests that measure the direct effect of tissue thyroid levels on the metabolic processes in the cells, but they are largely ignored by doctors of today. These include basal temperature and metabolic rate measurements. When it becomes necessary there is a recommended way of assessing tissue thyroid levels by using the ratio of Free T3 to Reverse T3; however, this is of value mostly when serum test results don't seem to align with symptoms. If interested in more detail, this link is a good source.
http://nahypothyroidism.org/thyroid-hormone-transport/#treatment
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