Thyroid Function...Labs May Lie

ScottTriGuy

Stop the harm. Start the research and treatment.
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In Sept my intent was to titrate up every 10 days until my temperature got to the normal range - I started at .0125mcg - my morning temperature went from 96.1 to 96.6 in the first month (and the pain of being cold lifted a lot) - but after that it didn't increase in spite of increased synthroid - when I was at .075mcg I just kept it there (partially coz I started Isentress and wanted to monitor one change at a time).

In early Feb I realized that for 10 days I had been taking .225mcg (oops) - but my temperature did not increase - so I dropped down to .0375mcg, but after about 3 weeks I started to feel more susceptible to the cold, so just a few days ago I resumed .075mcg.

I have not had any labs since starting synthroid. I told my doctor I titrated up and do not experience the pain of cold anymore, so she was fine with my dose and wrote a new prescription for .075mcg. (Originally it was .025mcg)
 
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Dr. Holtorf has some interesting literature online about thyroid levels in patients with other chronic diseases (specifically mentions CFS and others, anything that raises inflammatory cytokines IL-1, Il-6, C-reactive protein (CRP), and TNF-alpha, or maybe just raised some of these). https://www.holtorfmed.com/download/thyroid-fatigue-and-weight-loss/Thyroid%20Hormone%20Transport%20into%20Cellular%20Tissue.pdf

He gathers research and proposes using FT3/rT3 > 0.2 (pg/mL / ng/mL) to optimize thyroid medicine levels, and using natural thyroid or plain T3. The issue he sees is that there are different transporters in the pituitary than in other areas of the body, so lower than optimal dose of thyroid medicine can signal the pituitary to supress the TSH even if the transporters in the rest of the body aren't able to hardly get any thyroid hormone into the cells. So, one could have a low TSH and be hypothyroid.

In another paper (no reference at the moment but you could probably find it via google faster than I can), he talks about problems arising from iron saturation < 25 or ferritin < 70 ... apparently iron helps the deiodinases or transporters or whatever they're called get the hormones into the cells.

When the hormones aren't getting into most cells enough, they get into the pituitary no problem and drop the TSH. There's also cases where if your FT3 and FT4 tend to be low that the pituitary sponges up even more thyroid hormone so you can be low in FT3, FT4, and TSH all at once.

An elevated IL-2 could be from hypothyroidism, low amounts of active B2, or both. Thyroid hormone helps activate B2, and I'm not sure if the resulting flavoproteins and wide metabolic effects also affect thyroid and cellular transport of thyroid hormones. There are some interesting posts on the "B2 I Love You" thread trying to overcome insufficiencies of B2 or the active forms FMN and FAD. Increasing B2/FMN/FAD can also raise ferritin (unless taking something to rid it as it's raised?) so maybe that's a way it can help thyroid transport?

B12 is also related. A lot of people on this site have done or are doing Rich or Freddd's protocol with B12.
If low on active B2, FAD, then you may respond somewhat like having the CblC deficiency that Freddd has where inactive cobalamins have trouble/can't convert to active cobalamins mB12 & adB12, so glutathione ends up making you worse. If have both low glutathione from CFS/ME and get worse trying to raise it due to thyroid problems, bummer til thyroid is helped. http://vitaminb12deficiency.net.au/VB12Hypothyroidism.htm

There may be alternate ways when not enough thyroid hormone is prescribed to conquer hypothyroid symptoms, or somewhat make up for what thyroid hormone usually does.

If the links I posted aren't legit research, please let me know. I quickly glanced at the reference lists and they sounded like normal journals, but I'm no expert. I don't read/post here regularly - like everyone else here, illness takes it's share of my time and abilities, nor do I know how to do fancy messaging or how to correct my own posts yet.
 
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Athene*

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Hi @snowman. I was just discussing the ME/Methylation/hypothyroidism/b2 question with @Johnmac and @Kathevans on another thread. We were also talking about what our ideal ferritin levels should be. I came across a discussion with Dr Ben Lynch and a thyroid doc and they link to a study that shows that thyroxine (t4) is necessary to convert b2 (riboflavin) to FAD for the methylation cycle.

You need FAD to help MTHFR enzyme to function.

Because of the role of thyroxine (t4) in producing FAD, they advise that t3-only therapy might actually be a disadvantage. I was taken by that statement because I'm on t3-only and not doing great on it (persistently low Free t3 levels along with low TSH) and often getting icy cold spells.

They also point out that thyroid status does affect the expression of the MTHFR gene by modifying riboflavin creation. Even if your tests come back negative for MTHFR gene, the function of the MTHFR will still be compromised if thyroid levels are not right.

The warn that too much thyroxine can do more harm and interfere with proper function of MTHFR enzyme, causing an overdrive of methylation cycle. So that would be in the case of hyperthyroidism, or taking too much thyroid meds (t4).

I can link to their youtube discussion here if you're still around, or if anyone else wants it.

I'm trying to decide now whether to switch to more t4 instead of t3-only or whether I need to supplement b2 (riboflavin) like the biochemist guy advises - the one @Johnmac goes to for the b12 transdermal oils (which people are also having great success with).

I would love any comments from any thyroid sufferers...I don't want to end up over-driving the methylation cycle with too much b2 or thyroxine either, so how much of these does one take or can one eventually ditch the thyroid meds, as @Johnmac has been able to do?? Very interested in your comments re b2 and ferritin also because I have a ferritin issue too...
 
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@Athene* , this is very interesting. Could you please point me to the thread where you and @Johnmac c and @Kathevans are discussing so we can get this all in one spot?

One of the papers i posed above shows both T3 & T4 involved in both steps (B2 to FMN and FMN to FAD). Some lost chart I saw said both T3&T4 were involved in the first step, but only T4 in the second. Btw, Riboflavin Kinase (first step gene) uses Zn and Mg as cofactors, and FAD Synthase (second gene) uses Mg as cofactor.

One strategy may be to supplement FMN, that way skipping the first step to preserve more T3 & T4 for the 2nd step to produce FAD. Unless you've had your thyroid surgically removed, it still does make some T4 (and other hormones), so it may be enough to cover your needs.

I posted a MISTAKE about the ratio ...
it's supposed to be FT3/rT3 GREATER THAN 0.2 that is good. LESS THAN means hypothyroid tissues. If your FT3 is low, then that would lower your ratio making you more hypothyroid and freezing. If you add in T4, part of that gets converted to rT3 again lowering your ratio, putting up a greater obstacle for thyroid hormones to enter cells, and making you even more hypothyroid and freezing.

I'm going to hunt around and see if I can figure out how to correct my above post.

If your FT3 is still low, perhaps you're not taking enough of it. The first paper proposes that TSH is not of value in CFS/ME, and just look at ratio of FT3 to rT3 (or possibly sex hormone binding globulin). If you're not taking nearly enough T3, then the ratio could be quite low.

The approximate doses that think I remember reading as 'working' for people (on the stop the thyroid madness site, I think) is around 2-3 grains of dessicated or around 90mcg T3 alone. Dr. Holtorf seems to think the FT3/rT3 ratio also helps determine whether you might do better on T3 alone or on dessicated.

I heard some years ago that ferritin of 70-90 was ideal for thyroid hormone transport into cells, but I'm wondering if there has been further development in that area.

Elevated IL-2 can be lowered using methylcobalamin and/or adenosylcoblamin. We need enough thyroid and enough FAD to activate cobalamins, and deficiency of either can elevate IL-2. So, taking lots of active cobalamins could overcome some of the symptom cascade by reducing the amount of thyroid and FAD that are needed overall? However, there'd still likely be the danger of taking things that inactivate cobalamins, so you'd still have to avoid glutathione and nitrous oxide or nitric or whatever it is that the dentist uses, and other things that i'm not aware of. If you use high dose transdermal B12, whatever happened to inactivate B12's would be more quickly overcome. Fixing thyroid and/or B2 problems may fix the B12 problem unless one has a CblC genetic disorder. May fix it enough that it's possible to benefit from taking glutathione then.

I don't understand how the methylation cycle would be overdriven with high dose T4 if not much gets into cells, or maybe it would in some cells and not in others depending upon which ones have which types of thyroid transporters, but it sounds like most are supposed to be kinda slow on transporting T4?

Is the methylation cycle in ALL cells?

Which cells have the most effect on the labs or signs people use to judge methylation status, and what type of thyroid transporters do these cells have?
 
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@Athene* @Johnmac and @Kathevans, Can someone please look at http://vitaminb12deficiency.net.au/VB12Hypothyroidism.htm and interpret the diagram that shows riboflavin to FMN to FAD? I have had next to zero formal education in chem/biochem.

The first step says "ATP T3/T4" and the second step says "AMP T4/T3". Do these mean that T3 & T4 are required for the first step, or that T3 changes into T4 while making AMP that is required for this step, or does it mean something else?

Similarly, does the second step mean that T4 & T3 are required, or that T4 changes into T3 while making AMP, or does it mean something else?
 

Athene*

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@snowman Thanks very much for your replies. I have linked to the earlier thread I mentioned, below.

You're right about me being possibly low in t3 - I've only managed to get up to to 25mcg t3 (plus 1/2 grain Erfa natural dessicated thyroid) without my adrenals crashing. Even with the small thyroid dose I'm on, I need 20mg hydrocortisone daily. I'm hoping that will improve now I'm on the high dose metylcobalamin and methylfolate and adenscobalamin (Freddd protocol). I've been on t3-only because of low cortisol and iron problems so most likely have high reverse t3, but never got it checked. I've tried t4 only (levothyroxine) - got worse, and NDT only - still miserably low t3 results, but again have never been able to raise past 2grains because of adrenals struggling. You're right about TSH too - it behaves very strangely with ME/CFS - mine is always almost undetectable even in the presence of low t3...

I'm thinking about your FMN suggestion. I just wonder why @Freddd is so adamant that we should keep b2 low (since he says that b1, b2, b3, if not kept low, will raise folate needs to insatiable level...)??
 
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Athene*

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@snowman This is the link to the thread with @Johnmac and @Kathevans It evolved from somebody else's question on potassium needs
http://forums.phoenixrising.me/inde...eath-b12-malabsorption-potassium.41731/page-2

About your questions - I'm not educated in chem/biochem either. Maybe the study that Drs Lynch & Christianson refer to would help? Or if @Johnmac could get Dr Greg, the biochemist, b12 oils guy to answer your question?

The Drs Lynch & Christianson youtube discussion is in the thread above. Here it is again:

 

Gondwanaland

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P.S. I'm told @Gondwanaland is well-versed in thyroid issues. She might want to take a look at this thread too, and the earlier one I linked too...
It will take me a while to read everything that has been posted here, but meanwhile I can post about my experience:

L-T4, B2, Mn and estrogen raising herbs make me feel extremely hypo.

When I took L-T4 my TSH normalized, even my antibodies dropped a little for a while, but it was the period when I felt most hypo in my life and had to take an antidepressant.

When I started taking compounded T4/T3 I was able to ditch the antidepressant.

Now, even though I still don't supplement Selenium consistently because I don't feel any benefit from it, if I get a blood test after I have been supplementing with Se for a while, my Reverse T3 lowers (I think the reason why I don't feel any improvement is because my estrogen is too low, and if I up my T3 intake I immediately suffer from sweat bouts - however I haven't found a way to up my estrogen so far without feeling hypo - probably I will have to be consistent with Se and am working on it).

My conclusion is that I get hypo when I take anything that raises T4 (poor T4->T3 conversion).
If I raise my T3, I get sides from low estrogen.
I haven't been able to raise my estrogen without hypo side effects so far.
I am working on getting consistent with Se supp right now.

PS this year I switched from sea salt to iodized salt - didn't help with estrogen of course, but I don't have cold hands and feet anymore.
 

Athene*

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Thanks for this @Gondwanaland I have had the same issues with estrogen. And I never knew why, but like you, I feel worse when I take any kind of magnesium - though recently magnesium glycinate seems to be tolerated a bit better. Why would that be? Interesting that B2 made you hypo...I'm glad you mentioned that.

I'm on combined t4/t3 (Erfa ndt) the last 3 days and the constant diarrhoea (my worst low folate symptom when crashing) has stopped for two days now...maybe I needed some thyroxine after all.... I supplement Se 200mcg daily. I never had thyroid antibodies though I have read it helps with t4-t3 conversion. The only antibodies I had were for gluten, and coeliac was confirmed on gut biopsy. I was prescribed thyroid meds 15 yrs ago with aTSH of 7.5, then over the years of small-dose treatment, TSH was undetectable even in the presence of very low t3. Some HPA axis dysfunction going on?

I do feel much better since the @Freddd protocol, about 5 weeks now, with some dips/crashes on and off, but generally much better. Have you ever done that? I'm hoping hypothyroid situation will sort itself out eventually...

My experience with estrogen is that when it rises it lowers both cortisol and free t3 levels. P5P (b6) seems to helping with levelling out hormones, along with the Freddd protocol of high methylb12, methylfolate, adenosylcobalamin (lots of potassium required). Vit C also helps adrenals, and PABA and Pantethine.

Could your sweat bouts be adrenalin surges? I can't raise t3 for this reason - it stresses my adrenals, lowering cortisol and increasing adrenalin. The only thing that enabled me to get to 2grains of ndt was taking 20mg hydrocortisone in divided doses throughout day (I intend to come off that asap, but 20mg is a physiological dose (similar to what the body produces), not a pharmacological dose (more dangerous) and it's a bioidentical hormone (unlike e.g. prednisone and other steroids). It stopped the awful boiling sweats/adrenalin surges within a few days. A very conservative teaching-hospital endocrinologist was prepared to prescribe this even though I don't have Addisons, but 'evidence of some kind of adrenal insufficiency' after blood and urine testing. He warned me not to go any higher and not to stay on it more than a couple of years...
 

Gondwanaland

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like you, I feel worse when I take any kind of magnesium - though recently magnesium glycinate seems to be tolerated a bit better. Why would that be? Interesting that B2 made you hypo...I'm glad you mentioned that.
I was talking about Manganese which is the estrogen mineral, and also needed for keeping T4 from oxidizing. Although it is possible that Magnesium also antagonizes thyroid, perhaps by lowering stomach acid, I don't really know the mechanism. I could never tolerate MgGLY due to hypoglycemia, so when I needed Mg I could only tolerate Mg Oxide. Nowadays if I take Mg I get low Calcium symptoms (related to low estrogen).
TSH was undetectable even in the presence of very low t3
TSH only responds to T4 anyway, It actually tells you nothing about active hormones.
I do feel much better since the @Freddd protocol, about 5 weeks now, with some dips/crashes on and off, but generally much better. Have you ever done that?
I am following a Paleo-ish diet instead, since the main result from taking methylation supplements is improved insulin sensitivity. So I am saving money with supplements and eating foods rich in methyl donors.
Could your sweat bouts be adrenalin surges?
It improves if I manage to raise estrogen a bit
 

Athene*

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I was talking about Manganese which is the estrogen mineral, and also needed for keeping T4 from oxidizing. Although it is possible that Magnesium also antagonizes thyroid, perhaps by lowering stomach acid, I don't really know the mechanism. I could never tolerate MgGLY due to hypoglycemia, so when I needed Mg I could only tolerate Mg Oxide. Nowadays if I take Mg I get low Calcium symptoms (related to low estrogen).

TSH only responds to T4 anyway, It actually tells you nothing about active hormones.

I am following a Paleo-ish diet instead, since the main result from taking methylation supplements is improved insulin sensitivity. So I am saving money with supplements and eating foods rich in methyl donors.

It improves if I manage to raise estrogen a bit
So glad you've found what works for you @Gondwanaland. Interesting about the manganese & magnesium.

Yep - true about the TSH/t4 action, but oddly, even when I was on T4 only (Levothyroxine), my TSH was low, with very low free T4.

I have no thyroid antibodies, so we differ there...

I had an unbelievably good day today, and improving all the time on the methylation supplements (marked improvement within days when I began these - I do eat lots of meat, but I seem to need the supps, for now, at least), plus going back to some thyroxine a few days ago - seem to need less mfolate now and my low folate IBS symptoms have vanished.

I walked (gently) for 25 mins, and bought a few groceries, had a shower afterwards. This is from someone who was looking into buying a shower seat a couple of months ago, because I couldn't stay standing long enough for a shower...I've probably over-done it today, but fingers crossed.....!
 
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Gondwanaland

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oddly, even when I was on T4 only (Levothyroxine), my TSH was low, with very low free T4.
This is not odd since TSH responds to T4 only
I do eat lots of meat,
What do you mean? A Palo diet isn't about eating high protein. It is about lots of folate rich foods, methyl donors (fats) and normal protein.
I walked (gently) for 25 mins, and bought a few groceries, had a shower afterwards. This is from someone who was looking into buying a shower seat a couple of months ago, because I couldn't stay standing long enough for a shower...I've probably over-done it today, but fingers crossed.....!
This is great news :thumbsup:
 

Athene*

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It IS odd. You see, the thing is that TSH should only be low when t4 is getting high. As in the case of HYPERthyroidism for example.

When somebody is HYPOthyroid (low t4), the TSH becomes high - the pituitary is signalling for the release of more T4 by increasing TSH

In the case of HYPOthyroidism being treated, TSH falls as thyroxine is replaced. That's why endocrinologists (over) rely on it.

My situation, again, is that when I have low t4, instead of the pituitary signalling the thyroid to release more, it actually signals to release less

Yes, I eat lots of folate-rich foods, methyl donors (fats) and normal protein. I still need high dose mb12, mfolate, and adocbl, for now. It's been life-changing for me. Fingers crossed!
 
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Gondwanaland

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even when I was on T4 only (Levothyroxine), my TSH was low, with very low free T4.
Well, you were taking L-T4, so obviously your TSH lowered. Mine lowered as well when I took it, despite it making even more hypo (high R-T3, low T3 and FT3)
Even now that I don't have hypo symptoms anymore, my FT4 is usually borderline low
 

Athene*

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No problem about the misreading. Good to hear you're not suffering hypo symptoms.

However, the TSH shouldn't have lowered in my case.
That's because the Free t4 blood test showed I was still very low on t4, and still very hypothyroid (because when I was taking Levothyroxine/t4 it was not a high enough dose)...so no reason for TSH to be lowering, and sometimes even undetectable. Really it should have been still raised, signalling a dose increase was necessary.
Even more odd was when I did increase the t4 dose and the Free t4 test subsequently showed a healthier level (with some improvement in symptoms), the TSH also increased, instead of falling.

So then they did pituitary micro scan and brain scans and all was normal, and then they resorted to the 'idiopathic' word...
 
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Gondwanaland

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IME TSH tends to lower markedly when one starts taking L-T4, even if FT4 remains low - I think it is the whole T4 that matters for the pituitary, no matter FT4. The same happened to me. And after a while TSH can raise again. My TSH is higher now that I take T4/T3 then when I took L-T4 only.
 

Athene*

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Yes, but your Free t4 is 'usually borderline low', so to me the increase in your TSH would make sense in that case. In my case none of it made sense, and TSH remains permanently suppressed. The relationship between TSH and Total T4, free T4, T3 was always skewed, no matter which form of thyroid hormone I took - levo t4, t3 & t4 combination, t3 only.

At this stage I no longer worry about what the TSH is doing. I focus on symptoms and check the free t3 level occasionally.

Several endocrinology professors half-heartedly speculated some HPA axis dysfunction, rather than specific thyroid dysfunction, partly because of TSH behaviour and also because of the absence of antibodies, but no solution was offered, and no form of thyroid hormone helped much.

I don't want to speak too soon, but if the last few weeks are anything to go by, it's the methylation support that's really helping, and helping the NDT to work now too, where it didn't before.

Thanks for your interest. And good to see that it looks like you're on the right road for your needs too.
 
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The site I posted above ( http://vitaminb12deficiency.net.au/VB12Hypothyroidism.htm) looks like it is Greg's site. It does refer to his B12 oils site, looks like it's an Australian website, the info is similar though more detailed, and the contact email initials start with "g". I found the answer to my question when I read his description next to the diagram more carefully.

@Athene* , the low thyroid hormones and low TSH still sounds to me a lot like the problem with thyroid hormone transport into the cells that Dr. Holtorf speaks of in his paper above. However, going up on thyroid hormone can make you worse unless your adrenal function or replacement is ideal. Also, using the preparations with T3 can make for worse symptoms unless iron is high enough, whatever "high enough" is.

For B2 worsening things in hypothyroidism, it could use up more of what little thyroid hormones are available to convert B2 to FMN, so using FMN instead of B2 could help give flavoproteins without using as much thyroid hormone. Also, with celiac disease, FMN may be a better option since B2 may not be absorbed as easily.

The celiac-hypothyroid-hypoadrenal also could be early polyglandular autoimmune syndrome type 2, and unless the lower estrogen is due to menopause, hypogonadism can be part of the PAS. Maybe your endocrinologist has looked into this already. Or once thyroid replacement can come up, hopefully some of the other endocrine problems will normalize. Your thyroid medicine doesn't have gluten in it, I hope, or something else you may be sensitive to due to celiac disease.

I can see how B12 and 5-MTHF methylation supplements can have far reaching effects (not sure how helped tolerate NDT but happy for you). If some form of B2 isn't in there enough, we may be missing helping all the other metabolic processes that depend on FMN and FAD, and thyroid hormone may take care of the B2 metabolism once you get enough.

Wild guess, but I wonder if too much B2 overdriving methylation causes way too fast multiplication of cells and an increase in need for 5-MTHF for all those new cells. I read something about this, can't remember where, don't know if recalling correctly. Was it one of Rich's posts or papers?

The website that seems like it's Greg's talks about methylation with folate and b12, but also talks about an alternate way of boosting methylation with B2 and I think also B12. There is a page from that site that talks specifically about CFS/ME.

Thank you for the video link of Drs. Lynch and Christianson. At 36 minutes, they talk about hypothyroid patients needing more flavins, especially FAD. However I'd think that it doesn't matter as much what thyroid hormones you have in serum, the important part is what has made it into the cells as far as the B2 to FMN to FAD goes. It looks like both T3 and T4 are involved in the first conversion and at least T4 in the second. The T4 transporters into the cells get stopped up more easily than the T3 transporters, and rT3 is one thing that blocks the T4 transport (another is low adrenal function). So I'd think we need some T4 (which even the hypothyroid patient naturally makes) but not enough to make too much rT3 from it.

My brain is too fizzled to proofread this post.