Brain fog and exhaustion and despair over family problems are rendering me incapable of resolving anything.

[Mugs19]

I have the hazy memory of reading on various articles that there is no test which can tell you if your cells actually take up and utilise what T3 is produced and circulating in your blood. You can have a wonderful blood result showing plenty of T3 but you won’t feel any better if your cells aren’t using it properly, especially likely if you have the faulty DIO2 gene like me. Can someone who knows the facts about this let me know. I have an appointment with my endo on Tuesday and would like to get this straight in my head.

[SeasideSusie Remembering]

I reckon DippyDame might be able to help here

[Mugs19 in reply to SeasideSusie]

Thankyou for your speedy reply. I will try to digest this sometime later when there is some peace and quiet here. Just a bit worried that it’s all beyond my very limited comprehension the way I am functioning these days.

[DippyDame in reply to SeasideSusie]

I'll try!

[jimh111]

The cells invariably take up the hormone but it is possible it doesn't bind to receptors. The only way we can get an idea of how well the hormone is working is by looking at signs and symptoms. Things like cholesterol level, SHBG, pulse rate give a bit of information but are not conclusive.

[Mugs19 in reply to jimh111]

Thankyou so much for your reply. I had a feeling it wasn't straightforward and that probably the only way I am going to know is if a decent reading in my bloods makes me feel better - or not. Will have a look at sites already suggested.

[Smorzando in reply to jimh111]

Could you elaborate on how SHBG is affected? I've previously been found to have very high (over range) levels but have never been able to determine what that might mean. This was years before my Hashi's diagnosis.

[jimh111 in reply to Smorzando]

SHBG correlates with liver function and the liver has TRB1 receptors and so is a marker for thyroid hormone action on these receptors. Unfortunately, the 95% reference intervals are very wide and so in individuals SHBG is a poor marker for thyroid hormone action. It does reflect thyroid hormone action but not well because we each differ so much in our normal SHBG levels.

[Smorzando in reply to jimh111]

So, would SHBG tend to be high, or low, in cases of low thyroid function? (I appreciate what you're saying about the reference intervals)

[jimh111 in reply to Smorzando]

It would tend to be low in hypothyroidism but treat it as a small piece of the overall puzzle. There could be forms of hypothyrodism that don't affect SHBG.

[radd in reply to Smorzando]

Smorzando,

SHBG raises with elevated thyroid hormone so theoretically should decrease with low but is often normal due to a change in the isoforms caused by inadequate thyroid hormone.

SHBG can also raise if you are testosterone dominant or even taking HRT, a contraceptive pill or are over replaced with thyroid hormones that aren't working well so still inducing hypo symptoms & a sluggish liver that wouldn't be metabolising thyroid hormones well.

So although good liver health should theoretically indicate good working thyroid hormone receptors & metabolic processes they can become pretty skewed by the exact conditions we are trying to evaluate.

Evaluating LDL cholesterol & lipids alongside other gives a better picture as jimh111 has said.

[Smorzando in reply to radd]

Thank you - complex stuff and I can't pretend that I understood all of that! My over-range SHBG was found about 8 or 9 years ago now, many years before being diagnosed with Hashi's or being on thyroid hormone replacement; no contraceptive pill, no HRT, low testosterone levels. My GP was flummoxed by it as well; despite it being the highest level she'd ever seen, she couldn't offer my any explanation! Looking back I wonder if was perhaps going through an early Hashi's 'hyper' phase.

[DippyDame]

Correct, there are no tests to measure cellular T3!

FT3 can appear normal, even high, but you still feel rubbish but medics will tell you that you are "normal" because lab results say so. Rubbish...."normal is an anathema to thyroid patients!

Why? The T3 in the serum does not become active until it has entered the nuclei of the cells, via T3 receptors.

For a minority of people this does not happen effectively which means they are "running" on low active cellular T3...result we feel unwell. The tissues become hypothyroid.

A form of Thyroid Hormone Resistance (RTH) exists in that case, which means there is a "barrier" preventing the T3 reaching the point where it becomes active and does it's work to keep the body healthy.

RTH can be caused by genetic variants in alpha and beta receptors, this has been scientifically proven but it now appears that there are other acquired causes, possibly the result of other genetic variants which have not yet been identified by research.

To improve health the resistance has to be overcome!

The degree to which RTH occurs depends on how much free T3 reaches the cells, in my case I think the level slowly reduced over( possibly decades) as my health slowly declined and until my body could no longer cope. The lower the cellular T3 the worse you feel... in extremis, death is the result.

The solution is a supraphysiolgical dose of T3, the dose. The endo I saw would not entertain the possibility and would have left me on levo......deteriorating further.

This large dose acts as a " battering ram" pushing against the cellular resistance which should allow some of the dose to overcome that resistance and reach into the cells. The remainder will eventually be excreted. How much is required depends on the "push" required...

Blood tests are not useful in this situation so we have to dose by symptoms in a quest to feel well again!

There is more info plus usefull links in my responses in the following posts

healthunlocked.com/thyroidu...

healthunlocked.com/thyroidu...

Regarding the Dio2 polymorphism (which I have inherited from both parents) I doubt it has an impact on RTH, instead it impairs conversion particularly if homozygous. That however would have an impact by reducing serum FT3. I suspect, though I have no proof, that lower FT3, the result of poor conversion, might eventually reduce T3 receptor action due to inactivity.... and consequently lower cellular T3.

I'm afraid RTH is very complicated and I've only found out enough to enable me to improve my health. I'm aged 75 now so considerable damage was done before I learned what was making me very ill, and how to treat myself. My journey took nearly 4 years without the input of medics, I am very much improved, though RTH has undoubtedly taken its toll.

I'm not sure how your endo might react if you try to explain this to him/her. If they are a diabetic specialist you may just get a blank expression, if a thyroid endo they probably only consider the TR alpha and beta variants and dismiss anything else ( been there when I briefly saw an endo).

I'm not a medic, just another patient who has had to look for answers!

Good luck in building the case you wish to present to this endo. Please keep us posted

[Mugs19 in reply to DippyDame]

Thankyou for your informative and helpful reply. How do you calculate the size of supraphysiological dose needed? It is so well- spirited of you and others who have achieved wellness to keep coming on here to try to help the rest of us. I would be so easy to sit back and say "I'm o.k now so I don't need to worry about other people."

[DippyDame in reply to Mugs19]

You are welcome...but it's no more that other people have done for me

Basically it depends how much it takes to make you feel better.Start low and increase low and very slow

[Mugs19 in reply to DippyDame]

Thankyou again. Advice noted and much appreciated

[jimh111 in reply to DippyDame]

Beware of saying the hormone doesn't enter the cells, a smart endocrinologist (rare!) will pick you up on this. The hormone invariably enters the cells but may not bind to receptors.

[DippyDame in reply to jimh111]

OK.. thanks

I understand it has to bind to the receptors, semantics let me down!!

I'm still polishing my L plates!!

[jimh111 in reply to DippyDame]

No problem, I'm a bit pedantic on this point.

[radd]

Mugs19,

You are right, there is no test for dysfunction at a cellular level. Only the felt well-being result when thyroid hormone replacement meds finally work as they should.

I can't see any of your TFT's to comment if cell resistance looks likely and you have switched meds and combos several times in the last year. Steering away from the cell resistance due to possible T3 nuclear receptor defects mentioned above, have you considered your elevated antibodies in both Graves & Hashi? These could be causing immense inflammation that can inhibit meds from working well by altering the enzymes activity (diodinases) that influence every part of thyroid physiology. This would include the cleaving thyroid hormone from the protein-carriers, the transporters that help them into the cell, entering the nucleus and binding to nuclear receptor proteins.

Your nutrients levels are good and you are supplementing well (curcumin helps my inflammation no end, I still love it [tumeric curcuminoids]). I am not convinced regarding your iron. No matter what the other markers are, deficient ferritin is not normal and would usually be a first line indicator of iron deficiency. Have you had a full iron panel as only those results in conjunction with the FBC will give a clearer picture?

Many members are low in iron because of gut absorption issues caused by low thyroid hormone as it is only adequate working thyroid hormone that stimulates the production of RBC & haemoglobin synthesis, etc, making iron work properly. Low iron induces low thyroid hormone as is a major player in the making of (TPO) & therefore it is a vicious cycle as iron deficiency may be both the cause and an effect of hypothyroidism (although I realise yours is combined with RAI). Iron levels can be hard to raise as the body has safety mechanisms in place to prevent toxic overload that go into overdrive when suddenly a load of iron is introduced. Think slow & steady a bit like introducing T3. You've had a rough ride & are doing really well in trying to raise ferritin & reduce antibody levels through the usual means of gluten free, etc which might also help your gut issues.

Adequate cortisol is also required for good hormone synthesis but your adrenal results showed suboptimal cortisol patterns and your life sounds pretty busy. Stress will be heightened from feeling ill let alone other life stressors, so if this were me I would include some Vit C and adrenal support to try encouraging better cortisol levels. I take Ashwagandha Extract that balances cortisol levels. Some say Hashi suffers shouldn't take it but like the curcumin it has worked wonders for me and has some anti inflammatory properties. Androgens are quite individual as depend so much on your make up and there are plenty to choose from.

Doctors/endos are rarely interested in the nutrition that aids good thyroid hormone synthesis as their sole focus is usually on that TSH level & ranges. Good luck on Tuesday.

[Mugs19 in reply to radd]

Thankyou so much for this information and for taking the trouble to help me. I am in awe of all you people on here who have such understanding of the way things work. I struggle and when I think I have got it, I can’t retain it. My memory is not what it was. One thing confusing me is your comments about my high antibodies as it is usually put forward on here that antibodies don’t cause problems, they are the results of attacks on the thyroid by the immune system and in themselves, nothing to worry about.

[radd in reply to Mugs19]

Mugs19,

Thyroid antibodies are the result of the attack but it doesn’t mean they are not extremely damaging. Hashi is when large numbers of lymphocytes (WBC’s) accumulate in the thyroid, driving that auto-immune process where TPOAb attacks TPO enzyme & TGAb attacks thyroglobulin protein causing gradual destruction of thyroid gland follicles. Therefore, it is a thyroid issue but only secondary to the autoimmune issue that must be considered for well being to occur.

The level of thyroid antibodies doesn’t always correlate with the level of severity the immune system has been compromised, evidenced by some people living healthy lives with elevated thyroid antibodies, whilst others become extremely unwell with low. Also some have one antibody type, whilst others have all, and because none are considered as damaging to overall health by the medical profession, they are deemed unimportant but any autoimmunity increases some form of inflammation by its very nature, and any swelling should be encouraged to reduce.

Inflammation describes the release of chemicals and messengers that create irritation and swelling inside your body. A small amount is good as how the body heals itself using WBC to attack & kill pathogens, etc & with-holding iron by transferring into storage (ferritin), but long term elevated inflammatory chemicals stimulates the immune system to further release more that eventually interferes with the normal cell function by damaging blood cell walls. This is what causes symptoms such as puffiness, muscle or joint pain, abdominal issues that create the beginnings of intolerances.

Think of asthma, arthritis, food allergies that inflame & damage the intestinal lining, and how acute phase proteins are used as part of a diagnosis tool for certain conditions, ie CRP, ferritin, haptoglobin, etc, and changes such as in ESR which when raised is a marker for coronary heart disease. There is even a direct inverse correlation between raised CRP (caused by inflammatory cytokines) and reduced tissue T3 levels that no GP would acknowledge or even know.

As amongst a whole host of complex physiologic processes all mediated by the immune system high inflammation can suppress the HPT axis (hypothalamus-pituitary-thyroid), decrease both the number & sensitivity of thyroid hormone receptors, and impair conversion of T4-T3. Therefore, thyroid antibodies can directly or indirectly impair our thyroid hormone replacement meds from working well.

On top of all that elevated inflammation (high antibodies) predisposes us to other autoimmune conditions. What started off as Hashi hypothyroidism that even when optimally medicated with replacement hormones is still accompanied by aches and pains, post nasal drip, recurring UTI’s or fungal infections, wounds that don’t heal, dry itchy skin, more intolerance of foods, dairy, alcohol, heat, scratchy clothes, anything and everything, and then more autoimmune conditions such as PA, Type 1 Diabetes, RA, Sjogrens, etc and once we get into that reactive cycle it is difficult to get out unless inflammation is reduced.

Given that many forum members have long term illness, perhaps multiple conditions and troubles with thyroid hormone replacement meds working, it is prudent to assume some inflammation to be a part of or the whole cause of their problems, ie reduce the inflammation and multiple ailments clear up as meds start to work properly and we regain well being. That's why many members have found going gluten/dairy free has improved their symptoms as the immune systems reactivity calms and all intolerances lessen. Of course if gluten/diary isn’t the trigger then it won’t make any difference and there can certainly be a degree of genetic & environmental factors involved.

Books like The Root Cause by Isabella Wenzt explain it well. Also Datis Kharrazin on how functional medicines can help restore an immune system ravaged by Hashi.

[Mugs19 in reply to radd]

Thankyou for your very detailed reply. As I have often said, I am in awe of the knowledge and dedication shown by the members on here. I feel humbled as well as grateful. I’m not sure I can live up to these standards, but will try. Much more reading and acquisition of knowledge is necessary. Will do my best. Many thanks.

[radd in reply to Mugs19]

Mugs19,

Don't get too caught up with the antibody thing as they are only numbers. We feel if inflammation is present & we know when it goes coz we feel better. You are supporting your body well with the right supplements. Also symptoms can lag behind good biochemistry.

If I were you I would be looking firstly at that iron by asking your GP for a full iron panel to eliminate anaemia. Thyroid hormones meds are hugely dependant on adequate iron levels.

[Mugs19 in reply to radd]

Thankyou again. Am trying to sort it by eating more liver. Stir fry liver and pineapple tonight and liver and bacon last Wednesday plus mid morning snack of chicken liver pate daily. Blood test I’ve just had for endo tested B12 & folate, ferritin and serum folate, so when he tells me my results hopefully on Tuesday, I will consider full iron panel test again. I value your help, best wishes.