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

Iritu1021

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TSHI in my understanding is pituitary sensitivity to TSH and TTSI is thyroid cellular resistance (transport). @pattismith , is that how you interpret it?
@pamojja , what happened between this year and the last two years? did you change your thyroid meds? your numbers have changed quite a bit. Your GD is pretty low which means your T4 is not getting converted to T3. What are your symptoms?
 

pamojja

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What are your symptoms?
End of 2008 had a 80% blockage of my abdominal aorta diagnosed, due to a painfree-walking distance (intermittent claudication) of 3-400 meters only (and a 60% walking disability). 2012 the whole year a chronic bronchitis (diagnosed as COPD I, asymptomatic since resolving the bronchitis). By beginning of 2016 PAD symptoms ceased (with persistent high-dose Orthmolecular and Ayurvedic herbal medicine) and the walking-disability got revoked.

But could get a 50% disability instead for the remaining ME/CFS symptoms present since the beginning of this whole odyssey. Which for me are severe fatigue, back-pain and concentration difficulties after more than 5 hours work (mental), or after less than 10 hrs of sleep. And all these symptoms persisting till I can get a whole day of with complete rest (which often meant the whole working-week, until I reduced to 50% employment).

Your GD is pretty low which means your T4 is not getting converted to T3.
I suspect going gradually low-carb - beside low T3 illness syndrome - being responsible for low fT3, since right at the beginning (2009, when only having eliminated sugar) fT3 was still somewhat optimal. Sadly don't had any thyroid test before that date. However, avoiding pre-diabetes (again already wrongly diagnosed as T2D) had a higher priority for me.

did you change your thyroid meds?
Could have got T4 prescribed only, no T3. Which I didn't want because obviously T4 isn't lacking at all. Also because once got a fine of €260,- for a supplement order being accused of 'illigal medicine import', which on repeat would be fined up to €2600,- (custom just checks if any supplement contains any ingredient also found in prescription meds and then declares it as such, irrespective of it actually having been marketed as supplement only with no health-claims. In this case just TMG). Therefore didn't got anything through online pharmacies.

Did however use a non-standardized desiccated thyroid from Swanson, rather for having at least some placebo for my thyroid (80mg during the 3.- 5. year, and again from 7. to now), and could get my hands on some T3 on vacations (~20 mcg the 5th and 8th year) with no obvious effects on my thyroid numbers. On the contrary, my PAD remission actually occurred the year after having none of both.

However, due to the enlarged thyroid started Iodine/Iodide, by the 3th year having gradually titrated up to 12 mg/d. Then late last year up to 50 mg/d for a short period (for avoiding precautionary antibiotics for my root-canal extraction), before my ignorant non-supportive endocrinologist panicked because of allegedly dangerous high T4 and vitamin D :bang-head:. And immediately wanted me off of all Iodine, D3 and other hormone support (Dhea, Pregnenolone, Melatonin). For not loosing someone who at least tests all my hormones regularly, and because I like experimenting, I agreed and stopped or reduced most before the last test March the 5th this year.

, what happened between this year and the last two years?
Other than that, finally removed my only root-canal treated tooth (made in 2006 against my explicit non-consent), got my first 5 Mg-sulfate IVs (my worst nutrient deficiency having been non-responsive despite taking already 2.4 g/d of elemental oral Mg), and had my first excessive vitamin D3 serum test at 135 ng/ml (at the same average dose of about 8000 IU/d all these years), all this last fall. Not to forget my yearly 6-weeks vacation always Jan-Feb on a South-Indian beach. And quit one of my 2 part-time jobs a year ago.

Thanks for the explanations.
 
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pattismith

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sTSHI and TSHI correlate with pituitary-thyrotroph function
(secretion of TSH by pituitary to adapt to high or low T4 level)

TSH Index = TSHI
= log TSH + 0.1345 x fT4

sTSHI =(TSHI−2.7)/0.676.

if TSHI is low it means possible hypopituitarism

https://www.ncbi.nlm.nih.gov/pubmed/19226261

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544290/

"The Thyrotroph Thyroid Hormone Sensitivity Index (TTSI, also referred to as Thyrotroph T4 Resistance Index or TT4RI) was developed to enable fast screening for resistance to thyroid hormone."

TTSI, like TSHI, allows an investigation of the pituitary thyrotroph function, although it is used to evaluate thyroid hormons resistance (in patients with genetic TH resistance) whereas TSHI was used to evaluate pituitary activity. (in patients with hypopituitarism).


TTSI=100[TSH][FT4]/lu


https://en.wikipedia.org/wiki/Thyroid_function_tests

@pamojja

considering your latest panel (if I assume you don't take any TH supplement),
your GT is high, which is consistent with iodine supplementation
your GD is very low which means you have hypodeiodination by D1 and/or D2 (this is rather constant through the years of your testing)
your TTSI is very low which means your pituitary is highly sensitive to TH

Low GD and Low TTSI are found in Low T3 syndrome, so you may be concerned.
A dosage of rT3 and a fT3/rT3 ratio would be additional parameters to support this possibility
 

pamojja

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Thanks @pattismith

Low GD and Low TTSI are found in Low T3 syndrome, so you may be concerned.
I am for more reasons than low T3 illness syndrome alone.. But my docs abide in the bliss of ignorance. Since that's something they have not in their manuals to treat.

A dosage of rT3 and a fT3/rT3 ratio would be additional parameters to support this possibility
rT3 isn't available here. And I already to have all indications for assuming it being high already.
 

pattismith

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Thanks @pattismith



I am for more reasons than low T3 illness syndrome alone.. But my docs abide in the bliss of ignorance. Since that's something they have not in their manuals to treat.



rT3 isn't available here. And I already to have all indications for assuming it being high already.
Would he do a Growth hormon + Insulin Growth factor testing?

I have the Low T3 syndrome, and I am currently waiting for my GH + IGF test.

I don't have any critical illness, nor obstructive chronic respiratory illness, nor Crohn disease, not a cancer that I am aware of, so I am currently investigating other illnesses that can disrupt my deiodinase function. I believe Growth Hormon deficiency is something to rule out.

If nothing shows up, I will start supplementing to raise my GH level (melatonine, etc).

Also I try to avoid any supplement that can disrupt my D1 and D2 function (I stopped Lipoic acid and Carnitine).
 

pamojja

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Would he do a Growth hormon + Insulin Growth factor testing?
..

Also I try to avoid any supplement that can disrupt my D1 and D2 function (I stopped Lipoic acid and Carnitine).
Thanks for the tips, got some data but nothing suspicious here:

hgh.png


Incidentally had my lowest ALA intake in 2016 (200 mg/d compared to 300 in average throughout the years. And 1.1 g/d carnitine compared to 1.3 g/d in average).
 

pamojja

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I don't have any critical illness, nor obstructive chronic respiratory illness, nor Crohn disease, not a cancer that I am aware of, so I am currently investigating other illnesses that can disrupt my deiodinase function.
Actually don't have any reason to search any further for even more reasons causing NTIS:

.. a very complex previous medical history:

Pneumonia at birth, fever seizures with 2, meningitis with 7, X-ray found tubercle with 20, Palmoplantar pustular psoriasis, only 12 teeth remaining at age 29 (due to tetracycline treatment as new-born), 7 malaria attacks (4 of which the at times deathly falciparum), amoebic hepatitis (enlarged liver), spondilodiscitis and rhinitis.

2 years before my PAD diagnosis a very stressful job (which I quit just before the diagnosis), schistosomiasis, cystitis, a myopericarditis, and finally my first root-canal (without giving permission!). With the chronic bronchitis I also got a diagnosis of COPD (symptom-free after the bronchitis) and T2D (controlled with diet, which I would rather classify as prediabetes).
PS: last year a brain MRI found an old infarction of the left Cerebellum, I now can only guess when that occurred..
 
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Iritu1021

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@pamojja
Sorry, I'm trying to make sense of your history but I can't get the dates straight from what you wrote.
In 2009 you seem to have a picture consistent with iodine deficiency. Back in 2009 our deiodinases (GD) are working fine at that time and your GT is low and pituitary is somewhat resistant which probably implies that it believes the thyroid levels - at least periodically - are too high for your body.

Then in 2010 you go low carb. Is that also the year when you went on iodine first?

Some of those years you are taking thyroid extract which would throw your labs off. I think you need to enter what you were taking every year into your chart in order to see the full picture.

You also might want to think about any new prescription medications that you went on in 2009/2010. Statins, for example, have been known to precipitate CFS in some people through CoQ10 depletion.

Vitamin D excess can decrease D1 expression and affect thyroid sensitivity so that could have played a role too
https://www.ncbi.nlm.nih.gov/pubmed/20097959

You should also look into ayurvedic herbs you were taking, a lot of them have effect on hypothalamic and thyroid function so it may provide some clues as well.

The biggest change this year is that your secretory capacity suddenly really went up - and it seems to correlate with TSHI, as if your thyroid became much more sensitive to TSH. It might have to do with removal of iodine or Vit D or something else. However, your original problem of impaired T4 to T3 conversion still remains.

If you're not getting enough calories it can downregulate your de-iodinases. If you want to stay low carb then try to do high fat/ high protein diet. Bile acids can be taken as a supplement and seem to have effect on Dio2 expression. Guggul extract (herb) can increase peripheral T3 conversion.

End of 2015/ beg 2016 you were not producing as much T4. Were you feeling better then? What were you doing differently?

Cortisol (may be related to your work stress) and estrogen (which may be affected by DHEA, pregnenolone) can also have an effect on peripheral deiodination.

You said T3 didn't change your labs but did you feel better on it? Did you take 20 mcg all at once or in divided doses?
 

pamojja

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@pamojja
Sorry, I'm trying to make sense of your history but I can't get the dates straight from what you wrote.
In 2009 you seem to have a picture consistent with iodine deficiency.

..Then in 2010 you go low carb. Is that also the year when you went on iodine first?

Some of those years you are taking thyroid extract which would throw your labs off. I think you need to enter what you were taking every year into your chart in order to see the full picture.
I took the 80mg, almost 1/3 of a capsule of Swanson Thyroid Glandular (Thyroxine Free) during the years indicated.
(80mg during the 3.- 5. year, and again from 7. to now)
But it never ever made any difference to my before and after thyroid lab results, or how I felt in any way. I can be stubborn ;)

I have every lab test entered in a google-spreadsheet, in a second all nutraceuticals I've taken throughout all this time. It's just too large, complex and would rather not post a link publicly. But if you're really indent on sifting through so much of overwhelming data - the big picture is really vast - I could PM you the link if you really wanted.

To be precise with the iodine-intake: in the period of 8.2009-3.2010 about 0.7 mg, 4.-11.2010 about 5 mg, 12.2010-7.2011 about 12mg per day - each recorded period 8 month in length, actually always gradually increasing for catching possible adverse event (which I never had), along with numerous other vitamins, minerals and phyto-nutrients.

You also might want to think about any new prescription medications that you went on in 2009/2010. Statins, for example, have been known to precipitate CFS in some people through CoQ10 depletion.
Never took prescribed meds. However, had numerous nutrient-deficiencies, also CoQ10. Which I realized only when starting to supplement 9 years ago, because always above 150 mg CoQ10 (half the dose with Ubiquinol) made terrible stress related (physical or mental) angina-like chest pains go away.

Vitamin D excess can decrease D1 expression and affect thyroid sensitivity so that could have played a role too
https://www.ncbi.nlm.nih.gov/pubmed/20097959
In female Sprague-Dawley rats with 1-methyl-1-nitrosourea (MNU)-induced carcinogenesis of mammary glands. I've been mostly vitamin D deficient, and the curve of my serum 25(OH)D does't seem to correlate with my curve of expression or sensitivity.

You should also look into ayurvedic herbs you were taking, a lot of them have effect on hypothalamic and thyroid function so it may provide some clues as well.
Beside many other benefits on all body systems, that's why I take them.

If you want to stay low carb then try to do high fat/ high protein diet. Bile acids can be taken as a supplement and seem to have effect on Dio2 expression. Guggul extract (herb) can increase peripheral T3 conversion.
Got about 68% of my calories from healthy fats, my weight never changed a jota (BMI of 20). Have been on Guggul extract since the beginning gradually increasing to 1.1 g/d till 2013 and staying at that dose since then..

End of 2015/ beg 2016 you were not producing as much T4. Were you feeling better then? What were you doing differently?
That was the time of my PAD-symptoms remission (peripheral arterial disease, usually considered non-reversible) and that alone of course made me feel hell of a lot better then. Less the realization that all along there were ME/CFS symptoms and now remaining. Did not do really much different, therefore accrued it to the synergistic effects of years in life-style modifications and supplementation. So yes, much joy about having remission with a non-reversible disease, but still all ME/CFS symptoms remaining as before.

Just realized that I actually already published my nutrient intake google-spreadsheet on an other forum post, where you could find a link to it. Also an analysis of all my substantial nutrient-intake increases before that significant remission in an additional post there.

Cortisol (may be related to your work stress) and estrogen (which may be affected by DHEA, pregnenolone) can also have an effect on peripheral deiodination.
The problem in my case everything synergistically does have effects (PAD, COPD, T2D, CKD, stroke, enlarged liver and spleen, numerous nutrient deficiencies). And that in dodo has of course repercussions on hormones too. I warned about the complexity, but here the hormonal piece to the puzzle:

hormones.png


So cortisol at that time has indeed been lowest in serum, highest in 24hrs urine. DHEAs highest ever. Estradiol normal. Nothing related to anything I did particularly different that time.

You said T3 didn't change your labs but did you feel better on it? Did you take 20 mcg all at once or in divided doses?
First time took 25mcg tabs sublingual in divided doses, second time the same with drops. Didn't felt a jota different.

Thanks for all your suggestions.
 
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Gondwanaland

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Due to a lab error, last time I draw blood they didn't measure total T4 (1 week ago). Can my other results (TSH, FT4, TT3, FT3) yield a result with the SPINA? RT3 wasn't ordered this time, but last time back in January it wasn't high.
 

Iritu1021

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@pamojja If you read my blog you will see that I have special interest in dysautonomia and thyroid connection because I have POTS. It is obviously not the same as PAD but they both involve microvascular blood vessels and in my case it is closely related to my thyroid imbalances. Everything in the body is intricately connected.

My blood vessels are highly reactive due to collagen effect so I can observe the changes very easily but I think the same changes can manifest in other peoples in different ways depending on their other genetic blood vessel properties. I read in the Comprehensive Textbook of Iodine that T3 causes arterioles to dilate, so deficiency of intracellular T3 would interfere with proper arteriolar dilation. I doubt that it's a random coincidence that your T4 has changed around the same time as your PAD symptoms improved. Alternative thyroid books are full of so called "incurable" medical conditions that suddenly resolved after the person going on the thyroid regimen that was right for them.
Your GD was better during that time so one explanation is that more T3 was being used up by the cells and therefore more T4 was being converted to T3. So while serum T3 didn't change much, the intracellular T3 could have been higher. Something at that time appears to have improved your thyroid resistance. Maybe the higher cortisol can be explained by the ayurvedic herbs or orthomolecular supplements affecting your HPT/ HPA axis.
 

Iritu1021

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Due to a lab error, last time I draw blood they didn't measure total T4 (1 week ago). Can my other results (TSH, FT4, TT3, FT3) yield a result with the SPINA? RT3 wasn't ordered this time, but last time back in January it wasn't high.
You don't need rT3 to run SPINA, only TSH, fT3 and fT4.
 

pattismith

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.Did however use a non-standardized desiccated thyroid from Swanson, rather for having at least some placebo for my thyroid (80mg during the 3.- 5. year, and again from 7. to now),
This means you take both T3 + T4, so when you run Spina, you have to tick "T4 substitution " and "T3 substitution" as well. In that case GD and GT are not given, because they are not considered meaningful.

You don't need rT3 to run SPINA, only TSH, fT3 and fT4.
@Gondwanaland
and you can still run it if you have TSH TT3 TT4, or TSH fT3 TT4 or TSH TT3 fT4, you have just to change it in each parameter's window
 

pamojja

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Maybe the higher cortisol can be explained by the ayurvedic herbs or orthomolecular supplements affecting your HPT/ HPA axis.
You mean higher in excretion and lower in serum? Could be. Which begs the question why this temporary change in hormone levels gave remission of PAD-symptoms only? And why that hormonal change didn't persist despite continuing with supplementation?

Therefore rather think it a short downstream effect of somethings else. Also don't think my PAD with a 80% blockage at the abdominal aorta - a tube with 1 cm diameter - can that easily compared to microvascular blood vessels. In fact, at that time of remission of symptoms the blockage was still the same. So only extensive revascularization (=angiogenesis) can explain my improvement.
 

pamojja

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Did however use a non-standardized desiccated thyroid from Swanson, rather for having at least some placebo for my thyroid (80mg during the 3.- 5. year, and again from 7. to now),
This means you take both T3 + T4, so when you run Spina, you have to tick "T4 substitution " and "T3 substitution" as well. In that case GD and GT are not given, because they are not considered meaningful.
The dose of T3 and T4 in 1/3 capsule of Swansons (it specifically says 'thyroxine free') must be that low that they can't affect thyroid numbers. And even if I leave out GD and GT from the years 3-7 and 7-9, it doesn't change the averages from now that substantial. So can save myself from that extra effort.
 

Wishful

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@Iritu1021, I suppose I could convince my doctor to order complete thyroid tests twice, but I'm lacking a good reason to. Tests that would result in treatment, or recommendations to do something would be worthwhile, but just knowing that one of the hormones alters a bit during the cycle isn't really useful. If I had a researcher who was interested, then it would be worthwhile. Even if It revealed something interesting, what comes to mind is that scene from 'Raiders of the Lost Ark', where the incredibly valuable weapon is marked 'top secret' and disappears into storage, to be ignored.

Thanks for pointing out the T2-fat-burner. Knowing that there is a T2 product available is good, just in case iodine doesn't quite do the trick. What I will do next time is try to start determining the minimum dosage I need. I don't want to mess up my body further. I should probably get some potassium iodide to see whether it's the KI or the pure iodine or the triiodide from the combination that does the trick.
 

pattismith

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The dose of T3 and T4 in 1/3 capsule of Swansons (it specifically says 'thyroxine free') must be that low that they can't affect thyroid numbers. And even if I leave out GD and GT from the years 3-7 and 7-9, it doesn't change the averages from now that substantial. So can save myself from that extra effort.
I think you missed what swanson thyroid glandular is:


What is Swanson Thyroid Glandular used for?
The Thyroid produces three types of hormones.

  • Diiodothyronine (T2)
  • Triiodothyronine (T3)
  • Thyroxine (T4)
One capsule contains 200 mg of dessicated thyroid.

Although I didn't investigate the amount of TH cow's dessicated thyroid contains, thyroid produces much more T4 than T3, so the product you are taking contains mostly Thyroxine.

(in humans, the hormones secreted from the thyroid gland are about 80–90% T4 and about 10–20% T3)

I think Swanson by writing "thyroxine free", just wants to say they didn't add extra T4 to the product, but it can be easily misunderstood.

edit: I found this table that gives you equivalence between dessicated thyroid and thyroxine intake:

https://academic.oup.com/view-large/52492317


the whole study is here:

https://academic.oup.com/jcem/article/98/5/1982/2536971
 
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Iritu1021

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You mean higher in excretion and lower in serum? Could be. Which begs the question why this temporary change in hormone levels gave remission of PAD-symptoms only? And why that hormonal change didn't persist despite continuing with supplementation?

Therefore rather think it a short downstream effect of somethings else. Also don't think my PAD with a 80% blockage at the abdominal aorta - a tube with 1 cm diameter - can that easily compared to microvascular blood vessels. In fact, at that time of remission of symptoms the blockage was still the same. So only extensive revascularization (=angiogenesis) can explain my improvement.
What do you mean by "excretion"? The serum level and intracellular level are not the same. What matters is how much T3 gets taken up by the cells. For many of us here ME/ CFS is largely due to intracellular hypothyroidism, which I believe is caused by various combinations of cellular thyroid metabolism errors, primary thyroid gland issues and either pituitary or hypothalamic dysfunction.

The blockage and blood vessel contractility are two separate issues. Abdominal aorta is a central, not a peripheral blood vessel. When you use the term PAD, it formally implies a disease of small arteries in your extremities.

I now approach chronic disease from functional medicine standpoint, which states that everything has "predisposition" and trigger. The best value effort should focus on identifying the modifiable triggers.

Thyroid hormone affects cholesterol metabolism, angiogenesis and small blood vessel diameter which while it may not directly cause, it could still aggravate pre-existing PAD by taking the blood vessel's ability to efficiently regulate its diameter. It would not affect large blood vessels like aorta, only very small blood vessels (capillaries). On top of that, both estrogen and thyroid do have an effect on angiogenesis. As you put it yourself - everything works in synergy.

p.s. I gotta say that I admire how well organized you are with your data! I wish I was that good with mine.
 
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Iritu1021

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I think you missed what swanson thyroid glandular is:


What is Swanson Thyroid Glandular used for?
The Thyroid produces three types of hormones.

  • Diiodothyronine (T2)
  • Triiodothyronine (T3)
  • Thyroxine (T4)
One capsule contains 200 mg of dessicated thyroid.

Although I didn't investigate the amount of TH cow's dessicated thyroid contains, thyroid produces much more T4 than T3, so the product you are taking contains mostly Thyroxine.

(in humans, the hormones secreted from the thyroid gland are about 80–90% T4 and about 10–20% T3)

I think Swanson by writing "thyroxine free", just wants to say they didn't add extra T4 to the product, but it can be easily misunderstood.

edit: I found this table that gives you equivalence between dessicated thyroid and thyroxine intake:

https://academic.oup.com/view-large/52492317


the whole study is here:

https://academic.oup.com/jcem/article/98/5/1982/2536971
good point @pattismith . The product may then be responsible for T4/T3 imbalance. I also agree with you that one should be careful with taking carnitine and ALA if there is a suspected hypo.