SPINA THYR a research tool to evaluate thyroid function, deiodinases activity, TH resistance

CFS_for_19_years

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I had never heard of T3 uptake before :confused:
FWIW, it's considered an obsolete test.
http://www.elaine-moore.com/Blog/tabid/60/Post/6948/The-T3-Uptake-Test
Lately, there's some confusion about the T3 uptake test, a test considered obsolete. This test doesn't measure thyroid hormone. In this test, T3 is used as a reagent to determine how well your binding (carrier, transport) proteins bind with thyroid hormone. Years ago, this result was used along with the T4 test result to get an idea of about how much free T4 was present. This calculated result is referred to as an FTI or an FT7. Today, free T4 is tested using the direct FT4 test. [...]
 

Wishful

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Thank you for running the numbers. I'm still skeptical about the interpretations though, particularly for patients with ME. I think that my ME is causing elevated kynurenines, which (picolinic acid) should result in elevated trh and thus elevated tsh. It seems to me that might look like T4 resistance. I would not be at all surprised if the software developers didn't take that possibility into account.

In 2001, shortly after developing ME, my first thyroid function test was normal. I didn't get a copy of those results, so I don't know whether it might have been barely within normal, but marginally abnormal in retrospect. The abnormalities from ME might have been lower and inconstant at the time, and the test just caught me at minimum kynurenine and tsh elevation. My tsh does drop if I take supplemental T4, so I don't really seem to be resistant to it.

I still think that the lack of noticeable effects from taking supplemental T4 or T3 (unless I take enough to feel jittery) indicates that I don't have a significant thyroid problem. Theories can be useful, but real-life observations are even more useful. My response to T2 is more likely due to abnormalities in cellular response to T2.

Supplemental T4 should add iodine to the body, since it's so effectively recycled, but it doesn't have the effect on me that iodine or T2 does. My guess is that supplemental T4 suppresses thyroid function--including T2 production--more than it boosts it by adding recycled iodine.
 

Gondwanaland

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Thank you for running the numbers. I'm still skeptical about the interpretations though, particularly for patients with ME. I think that my ME is causing elevated kynurenines, which (picolinic acid) should result in elevated trh and thus elevated tsh. It seems to me that might look like T4 resistance. I would not be at all surprised if the software developers didn't take that possibility into account.

In 2001, shortly after developing ME, my first thyroid function test was normal. I didn't get a copy of those results, so I don't know whether it might have been barely within normal, but marginally abnormal in retrospect. The abnormalities from ME might have been lower and inconstant at the time, and the test just caught me at minimum kynurenine and tsh elevation. My tsh does drop if I take supplemental T4, so I don't really seem to be resistant to it.

I still think that the lack of noticeable effects from taking supplemental T4 or T3 (unless I take enough to feel jittery) indicates that I don't have a significant thyroid problem. Theories can be useful, but real-life observations are even more useful. My response to T2 is more likely due to abnormalities in cellular response to T2.

Supplemental T4 should add iodine to the body, since it's so effectively recycled, but it doesn't have the effect on me that iodine or T2 does. My guess is that supplemental T4 suppresses thyroid function--including T2 production--more than it boosts it by adding recycled iodine.
Yes yes yes!
How can I discuss this with my dr???
 

Gondwanaland

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I think that my ME is causing elevated kynurenines, which (picolinic acid) should result in elevated trh and thus elevated tsh.
I wonder if LDN would help with that? Have you tried it?
I read that low vit A causes TSH to raise. https://www.ncbi.nlm.nih.gov/books/NBK285556/ Table 5

Supplemental T4 should add iodine to the body, since it's so effectively recycled, but it doesn't have the effect on me that iodine or T2 does.
What is your response to iodine? I am considering to take a little kelp iodine (~150 mcg) 1-2x weekly (and some vit A).
 

Wishful

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LDN was really effective at blocking perceived muscle aches for a year or so. It seems less effective at that now. It didn't do anything for other symptoms.

Years ago, something in a multivitamin/mineral tablet made a huge difference in my symptom severity. By testing vitamins individually, and then minerals, I identified the factor as iodine. However, taking iodine supplements continually did nothing; it was just the initial boost that reduced the symptoms temporarily. Much later, I was wondering about why iodine worked but T4 and T3 didn't, and asked myself the question: does the body use iodine for anything else. The answer was T2, which was known to have strong metabolic effects. I ordered some, tried it, and it was like the first boost of iodine I had: symptoms more or less gone, and I felt energetic again. However, again, it lost its effects after taking it for a few days...and then my symptoms rebounded (increased beyond baseline) by about the same amount as they had dropped, for about the same length of time. My guess is that taking more than one dose caused the thyroid gland to reduce its T2 production to compensate, and then it took a while to return T2 production to normal, leaving me with reduced T2 levels for a while.

After more experiments and data collection, I found that every 21 days, my symptoms increase in severity and stay increased until I take some supplemental T2 or iodine (a drop of tincture on bread). Then my symptoms return to baseline level for another 21 days. Occasionally I can go for longer before noticing the increase in symptoms, but haven't figured out what factors allow that. I don't anticipate the change (ie. checking my calendar for when the 21 days is up), but rather wait until I notice the increase in symptoms, and when I check my ME diary, it's usually 21 days since my last boost.

No one else has reported the same T2 cycle I have, so I can't really make any recommendations to others regarding T2 or iodine, other than to be aware that it may not be as simple as 'take daily supplements to feel better'. The important thing is to pay attention to your response to supplements.

As for talking to a doctor about it, don't expect much. I went to an endocrinologist, and his response was: 'Low tsh = hypothyroidism. Here's a prescription for T4.' When I pointed out that T4 didn't help me, but iodine did, and offered an alternative explanation (elevated kynurenines), he got angry and ended the appointment. He said I shouldn't 'Mess around with iodine.' If I'd listened to him, I wouldn't have the relief from the symptoms that iodine provides to me, and probably would have committed suicide to end those symptoms. There may be open-minded endocrinologists out there, but this one was very closed-minded. If I did need to see an endocrinologist or any other specialist again, I'd first enquire whether they're willing to accept non-standard problems related to ME. If they don't believe that ME is a real condition, they're not going to be much help.
 

Wishful

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Yes yes yes!
How can I discuss this with my dr???
I looked at your question again, and the image that came into my mind was you sitting on your endocrinologist and slapping him with a thick medical book until he admitted that maybe there's more to thyroid disorders than what's in the book. I'm not sure that there would have been any other way to get through to my endocrinologist. At least I'd have left his office feeling somewhat better. :)
 

Gondwanaland

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@Wishful Thank you so much for the reply.

I am not treated by endo. My practitioners are integrative drs, one specialized in vitamins, one in hormone balance and one in Metabolic Syndrome - which I do not have, but I see him because he reads current and past research. Now I finally also have an immuno looking into possible infections.

probably would have committed suicide to end those symptoms
Me too if I had to take LT4.
(elevated kynurenines)
Could you please summarize what this would imply?
 

pattismith

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I went to an endocrinologist, and his response was: 'Low tsh = hypothyroidism.
I think you are mistaken

"An abnormally high TSH means hypothyroidism: the thyroid gland is being asked to make more T4 because there isn’t enough T4 in the blood."

https://www.thyroid.org/hypothyroidism/

I read that low vit A causes TSH to raise. https://www.ncbi.nlm.nih.gov/books/NBK285556/ Table 5
"Abstract
Retinoid status with reference to beta-carotene and retinol has been studied in women suffering from hyper- and hypothyroid conditions. The interrelationship between the retinoids and triiodothyronine and thyroxine hormones has been established from the cases mentioned after estimation of the respective compounds from the blood serum. It has been found that there is an increase in beta-carotene and retinol in the hypothyroid and a decrease of the same in the hyperthyroid conditions respectively."

This means that in hypothyroidism (high TSH), vitA blood levels are higher
and that in hyperthyroidism (low TSH), vitA blood levels are lower


"Serum T3 concentrations also increased in both obese and non-obese vitamin A-treated groups (p < 0.001).
Serum T4 decreased in all 3 groups after treatment."

This is interesting, it means that vitA supplementation increases T3 , maybe by upregulation of 5'-deiodinases (D1and/or D2)
 

Wishful

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Yup, I meant high tsh = hypo. Brainfog, y'know. ;)

To Gondwanaland, kynurenines are the result of tryptophan conversion. Our cells convert TRP into several types of kynurenines, which are needed for various purposes. When our immune systems are active, the cytokines increase the conversion into kynurenines. Some of them, such as quinolinic acid, are probably responsible for some of the symptoms of inflammation: malaise, lethargy, pain, and suicidal moods. Picolinic acid elevates macrophage inflammatory proteins, which in turn elevate trh, and thus tsh. My cytokine profile did show elevated MIPs, and while that's not proof that picolinic acid was elevated (there might be other causes), it should explain elevated tsh.

In the early days of this disorder, long before I read about ME/CFS, I assumed it was some rare form of chronic inflammation, which would cause elevated IFN-g, which would elevated indole oxidase, which would catalyze more TRP into kynurenines. That was simple and logical. I had various observations, such as my response to TRP and exercise (which increases IFN-g 24 hrs later) that supported this hypothesis. Later I observed that sugars and starches would increase symptoms about 20 minutes later...unless I took BCAA's with the meal. Sugars and starches increase insulin, which increases TRP transport into the brain, where they'd convert into kynurenines. It still seems a logical explanation to me, and I haven't found any strong counter-evidence.

I tried a low-TRP diet for a long time, but it's hard to avoid TRP completely, and the body must keep larger reserves of it, since I didn't manage to feel better. High-TRP foods did make me feel worse, and TRP tablets made me strongly suicidal. If high-TRP foods make you feel worse, or insulin-boosting foods make you feel worse 20 minutes later, then I'd consider that more evidence that kynurenines are a significant factor in ME/CFS symptoms.

I'd like to try one of the drugs that alter kynurenine conversion, but they're not available for human use. They sound fairly safe, but no one has gotten them through the approvals process yet.
 

Iritu1021

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I also noticed an immediate boost in energy in iodine but always followed by rapid worsening in symptoms, which I assume are due to effect on TSH. I also have low GT on SPINA (2.1) however my GD is 28. How many micrograms of iodine exactly do you take? Is it a drop of Lugol's tincture? Seems like the effect is very much dose dependent and might depend on the form of iodine used. Maybe the solution is to just increase dietary iodine levels in order to avoid Wolff-Chaikoff or Jon-Basedow effect.
 

Iritu1021

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I think you are mistaken

"An abnormally high TSH means hypothyroidism: the thyroid gland is being asked to make more T4 because there isn’t enough T4 in the blood."

https://www.thyroid.org/hypothyroidism/



"Abstract
Retinoid status with reference to beta-carotene and retinol has been studied in women suffering from hyper- and hypothyroid conditions. The interrelationship between the retinoids and triiodothyronine and thyroxine hormones has been established from the cases mentioned after estimation of the respective compounds from the blood serum. It has been found that there is an increase in beta-carotene and retinol in the hypothyroid and a decrease of the same in the hyperthyroid conditions respectively."

This means that in hypothyroidism (high TSH), vitA blood levels are higher
and that in hyperthyroidism (low TSH), vitA blood levels are lower


"Serum T3 concentrations also increased in both obese and non-obese vitamin A-treated groups (p < 0.001).
Serum T4 decreased in all 3 groups after treatment."

This is interesting, it means that vitA supplementation increases T3 , maybe by upregulation of 5'-deiodinases (D1and/or D2)
Yes, I believe I read that retinoic acid upreguates D1.
 

Iritu1021

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Yup, I meant high tsh = hypo. Brainfog, y'know. ;)

To Gondwanaland, kynurenines are the result of tryptophan conversion. Our cells convert TRP into several types of kynurenines, which are needed for various purposes. When our immune systems are active, the cytokines increase the conversion into kynurenines. Some of them, such as quinolinic acid, are probably responsible for some of the symptoms of inflammation: malaise, lethargy, pain, and suicidal moods. Picolinic acid elevates macrophage inflammatory proteins, which in turn elevate trh, and thus tsh. My cytokine profile did show elevated MIPs, and while that's not proof that picolinic acid was elevated (there might be other causes), it should explain elevated tsh.

In the early days of this disorder, long before I read about ME/CFS, I assumed it was some rare form of chronic inflammation, which would cause elevated IFN-g, which would elevated indole oxidase, which would catalyze more TRP into kynurenines. That was simple and logical. I had various observations, such as my response to TRP and exercise (which increases IFN-g 24 hrs later) that supported this hypothesis. Later I observed that sugars and starches would increase symptoms about 20 minutes later...unless I took BCAA's with the meal. Sugars and starches increase insulin, which increases TRP transport into the brain, where they'd convert into kynurenines. It still seems a logical explanation to me, and I haven't found any strong counter-evidence.

I tried a low-TRP diet for a long time, but it's hard to avoid TRP completely, and the body must keep larger reserves of it, since I didn't manage to feel better. High-TRP foods did make me feel worse, and TRP tablets made me strongly suicidal. If high-TRP foods make you feel worse, or insulin-boosting foods make you feel worse 20 minutes later, then I'd consider that more evidence that kynurenines are a significant factor in ME/CFS symptoms.

I'd like to try one of the drugs that alter kynurenine conversion, but they're not available for human use. They sound fairly safe, but no one has gotten them through the approvals process yet.
Thyroid hormone has profound effect on serotonin so you might be observing downstream effect of your serotonin imbalance... I don't have kynurenic problems but noticed that 5-H1AA levels went down on thyroid supplementation and went up when I was low.
 

Iritu1021

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I can't wait to install this software when I return home in a few days! This research is what I was looking for all the time when thinking of thyroid...
Thanks @pattismith and @debored13 for sharing this useful information about SPINA Thyr. And thanks @Gondwanaland for calling my attention to this thread!!
Why I am so enthusiastic: I always had my thyroid labs largely within normal range, but with a lot of reading I saw some abnormalities in the constellation... I understand that exactly this is the main purpose of this software.

To anyone with orthostatic issues, here a few lines why thyroid is so important:
  • Decreased cardiac output is a major factor in orthostatic intolerance (Example: Table 2 on page 19 in this research shows the low values in POTS)
  • Thyroid is a reason for low cardiac output (reference): "Thyroid hormones have a variety of effects on the cardiovascular system that can greatly impact cardiac function (Figure 1). Hypothyroidism is associated with decreased cardiac output due to impaired relaxation of vascular smooth muscle and decreased availability of endothelial nitric oxide. This produces a cascade effect of increased arterial stiffness that leads to increased systemic vascular resistance" ............ "Cardiac echocardiography has demonstrated impaired relaxation in patients with overt and subclinical hypothyroidism. .... diastolic dysfunction from impaired relaxation."
The above addresses me 100%: I have POTS, lowish cardiac output, decreased availability of nitric oxide, increased systemic vascular resistance and diastolic dysfunction. Do you have orthostatic probs? I am happy to help how to calculate the above parameters, what measurements one needs from what type of cardiologist ... and nitric oxide you can (indirectly) test at home.

I am looking forward to relate all this to thyroid probs!
I'm in the process of trying to explain POTS and thyroid levels, taking into account TA (iodothyroacetic acid) which increases histamine. This table is probably not be necessarily accurate but I need some other people with POTS to help me figure out if I'm close or not. Maybe you can let me know if you fit into one of my descriptions and what your SPINA shows to help me sort it out better.
http://www.chronicfatiguediagnosis.com/2018/03/20/thyroid-inferno-the-eight-circles-of-hell/
 
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CFS_for_19_years

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I'm in the process of trying to explain POTS and thyroid levels, taking into account TA (iodothyroacetic acid) which increases histamine. This table is probably not be necessarily accurate but I need some other people with POTS to help me figure out if I'm close or not. Maybe you can let me know if you fit into one of my descriptions and what your SPINA shows to help me sort it out better.
http://www.chronicfatiguediagnosis.com/wp-admin/post.php?post=1277&action=edit
Your link led to a password-only web page. There was no place to register.

In the meantime I took a look at your website http://www.chronicfatiguediagnosis.com and was very impressed with what you have to say about thyroid treatment, especially the trendy stuff.
 

Iritu1021

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Your link led to a password-only web page. There was no place to register.

In the meantime I took a look at your website http://www.chronicfatiguediagnosis.com and was very impressed with what you have to say about thyroid treatment, especially the trendy stuff.
Sorry, I must have grabbed the wrong link. I meant my today's post dubbed "Thyroid Inferno: Eight Circles of Hell".
http://www.chronicfatiguediagnosis.com/2018/03/20/thyroid-inferno-the-eight-circles-of-hell/
Does the table I describe make sense? I see POTS as failure of T1AM and T3 to balance each other, resulting in various microcirculation presentation and neurotransmitter imbalances, which are not present in classical hyperthyroidism and hypothyroidism. Thanks, glad to hear you liked my blog. It's been both a labor of love and a product of necessity to try and make sense of all this...
 

Iritu1021

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https://academic.oup.com/endo/article/150/3/1108/2455550

This isozyme-selective processing suggests a specific biosynthetic pathway for endogenous T1AM production (Fig. 2) with either T4AM or rT3AM serving as entry points into the pathway, and these entry points would originate from decarboxylation of either T4 or rT3.
Therefore, taking T2 rather than T4 or T3 would bypass T1AM production.

@Wishful, which brand of T2 do you use and at what dose?

p.s. this may be why it didn't work for you over long term:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045230/
 
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Wishful

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@Iritu1021, I used San T2, and later San T2Xtreme (which added 3-3-T2, which didn't change the effects). One capsule (100 mcg T2) was enough to 'reset' whatever went wrong every 21 days. I didn't experiment to determine the minimal dose necessary. Both products have been discontinued, and I can't find another source of T2, so when my last few capsules are gone, I'll switch to iodine. I don't even know if supplemental T2 is healthier for me than supplemental iodine, so I'm not overly concerned that they discontinued the product.

The article about T2 depressing thyroid function might explain my experience. However, it could also be cellular response to T2. I don't see any way to confirm how it works. I'm just glad that it does work for me.

I don't think that my serotonin levels are significantly affected. There are two pathways in the brain for TRP: the 5-HTP-serotonin pathway and the kynurenine pathway. Tryptophan makes my symptoms dramatically worse. 5-HTP doesn't affect my symptoms (except for helping me get back to sleep if I get insomnia). Likewise, serotonin reuptake modifiers didn't affect my symptoms. I haven't seen any reason to suspect serotonin pathway abnormalities. My observations do strongly suggest kynurenine pathway abnormalities.
 

Iritu1021

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@Iritu1021, I used San T2, and later San T2Xtreme (which added 3-3-T2, which didn't change the effects). One capsule (100 mcg T2) was enough to 'reset' whatever went wrong every 21 days. I didn't experiment to determine the minimal dose necessary. Both products have been discontinued, and I can't find another source of T2, so when my last few capsules are gone, I'll switch to iodine. I don't even know if supplemental T2 is healthier for me than supplemental iodine, so I'm not overly concerned that they discontinued the product.

The article about T2 depressing thyroid function might explain my experience. However, it could also be cellular response to T2. I don't see any way to confirm how it works. I'm just glad that it does work for me.

I don't think that my serotonin levels are significantly affected. There are two pathways in the brain for TRP: the 5-HTP-serotonin pathway and the kynurenine pathway. Tryptophan makes my symptoms dramatically worse. 5-HTP doesn't affect my symptoms (except for helping me get back to sleep if I get insomnia). Likewise, serotonin reuptake modifiers didn't affect my symptoms. I haven't seen any reason to suspect serotonin pathway abnormalities. My observations do strongly suggest kynurenine pathway abnormalities.
The way you could confirm is to test your thyroid labs at the beginning and the end of your 21 day cycle and compare.
 

Iritu1021

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The way you could confirm is to test your thyroid labs at the beginning and the end of your 21 day cycle and compare.
I found this one online but I don't know where you are... http://mindandmuscle.net/articles/product/t2-fat-burner/
Since it's liquid it might be easier to microdose but you're probably right that you're better off just sticking with iodine. However, keep in mind that even one drop of Lugol solution (if that's what you're using) is a humangous amount of iodine for someone who has long standing iodine deficiency.
 

pamojja

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So..
GT is thyroids maximum secretory capacity
GD is sum activity of pheripheral 5'-deiodinases
TTSI is pituitary function related

But what means sGT, TSHI and sTSHI?

Added SPINA parameters to my regular thyroid tests of the last 9 years:

spina.png
 
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