No response to high dose thyroxine - why?

[Phlogiston]

Hello. I'm new on here, and hoping that someone has any idea about my lack of response to T4, based on their own experience, or physiological knowledge. I have many symptoms of an underactive thryroid but generally my blood tests come back in the normal range, and I have had a confirmation of Hashimotos. I have been on 150 mcg T4 for about 8 years. It helps, but I still suffer badly from exhaustion, depression, and "brain-fog" which have no apparent cause. I have recently obtained a private prescription for extra T4 which I have titrated upwards to see how much I need to take to feel better. I've now been taking 800 mcg per day (Almus) for a week and have had no response to it, good or bad - and I see no point in trying higher. I am baffled - I expected to feel better with increasing dosage, and then to feel worse as I start experiencing hyper symptoms like palpitations and trembling hands - but absolutely nothing. I've tried T3 previously and it didn't have any enhanced potency compared to T4, so possibly not a conversion problem. Any ideas about why that's happening in my crazy body and how I could go about addressing it?

For context, I also take daily a multi-vitamin/mineral, 1600 U vit D, and 1 g Vit C (slow release). Have cut gluten and dairy (as well as eggs and yeast) from diet, and reintroduced meat to see if that affects energy levels; however, the only dietary adjustment that significantly helps seems to be severe calorie restriction. I've booked for blood tests at GP surgery but can't have them until mid-July (I usually avoid them cos they just prompt a message on the system to reduce the T4 dose).

BACKGROUND: Have suffered from sleepiness all my life. Since 12 (now 48), different GPs in a variety of countries have said it sounds like hypothyroism but lab tests always said my thyroid's OK: do it's just the way I am, and I have to learn to live with it. Since birth of child at 40, exhaustion has been worse and helpful GP interpreted highish TSH and lowish T4 as hypothyroid (even though they weren't always outside range), and when I asked for antibody tests we confirmed I have Hasimotos. He prescribed levothyroxine at 150 mcg to try and get TSH to low end of normal scale, and he's been very good about ignoring the warnings on the NHS system that he's over-dosing me. Symptoms improved but didn't disappear. Being a scientist and of curious disposition, I decided to do some self-experimentation a few years ago: got some internet tyroxine and discovered that I needed about 800 mcg per day to get any hyper symptoms and discovered how nasty that was. But other friends get hyper symptoms with changes in dose of 25 mcg, so that puzzled me. Read all the "alternative" thyroid books but wasn't in a financial position to get private testing or meds then, so tried to get help through NHS. Got referred to Endo who did a variety of tests & said that adrenals were fine, I was peri-menopausal, and was Vitamin D deficient. He decided vitamin D deficiency was the root of my problems and prescribed 1000U Vit D: he wanted to bring down my T4 dose, but was persuaded to keep it up although would not increase it. That was about 4 years ago and vitamin D levels quickly became normal but exhaustion/brain fog continued. A friend who works at top US med school has a colleague endo who prescibes high dose VitD (5000 U/day) for her Hashimotos and on her advice I tried that with the help of my friendly GP - it might have helped a bit (or might have been placebo effect) but anyway the GP's bosses cut the dose and I haven't tried to keep it high. Told the Endo about the need for 800 mcg T4 to get hyper symptoms and he dismissed it as completely impossible. Then sent to "Fatigue" clinic, but they decided I didn't have CFS/ME/whatever (despite EPV positive result, which they decided must have been a lab mistake despite my yellow pallor: follow-up showed recent EPV infection which must also have been a mistake), and even if I did all they could do was recommend graded exercise which is my normal approach anyway. Next I was sent to the sleep clinic. No apnoea found, so I was diagnosed with "Idiopathic Hypersomnia", i.e. we agree you need excessive amounts of sleep, but we haven't got a clue why (because the Endo said there was not hormonal issues, they had already eliminated that as a possible cause). Nice to have a diagnosis to give the boss and say I'm not just lazy, but otherwise completely hopeless. So I can have as much Modafinil as I want to help me stay awake (it works, but all it does is shift the sleep debt to a later date). Likewise, I can have as many anti-depressants as I care to ask for (just switched from citalopram to venlafaxine which should be a little more stimulating). But God help the doctor who gives me more thyroxine. I just don't get it. Having gone through all the conventional routes available to me I'm now back to looking at those "alternative" books again, and hope that others who've been though this can lead me in the right direction to improve my health.

[shaws]

There is something called Thyroid Hormone Resistance and this is a link to an archived website, so some of the links within may not work. Besides of all thyroid hormones levothyroxine, being the most prescribed, is usually not the best. Natural Dessicated Thyroid Hormone,for instance, contains all of the hormones our own thyroid gland no longer produces, so if levo doesn't convert to enough T3 you are unwell.:-

web.archive.org/web/2010103...

There are also other topics at the top of the page which may interest you.

I must point out that this is an archived site so links within may not work. Dr Lowe died two years ago.

[Phlogiston]

Thanks for that reply shaws. It's really helpful to read about different types of resistance - very well elaborated information from Dr Lowe. If that's my problem, then the only approach seems to be loads of thyroid hormone as a supplement. Perhaps it is time for me to try the natural dessicated hormone, as you suggest. I shall use the site to get some recommendations on what to use.

[helvella in reply to Phlogiston]

"Loads of thyroid hormone" is not the only possibility. There are substances such as TRIAC and TETRAC which have at least been tried for some patients.

I suggest this chapter is of potential use:

thyroidmanager.org/chapter/...

Appropriate gene testing, and good interpretation/guidance from someone who understands, could be a very useful avenue. It might at least explain what is going on.

Rod

[Phlogiston in reply to helvella]

I've had a quick look at the literature on TRIAC and TETRAC which I hadn't heard of before: but they seem to be more for hyperthyroid patients though, as non-active analogues of T4 and T3. Or am I misunderstanding?

Do you know is there anywhere in the UK likely to be interested in doing genetic testing on this?

[helvella in reply to Phlogiston]

The full complexity of the condition appears sometimes to find both hyperthyroidism and hypothyroidism at the same time. I get the impression that is when TRIAC, TETRAC and even dextrothyroxine can have a role.

Afraid I don't know where such testing/investigation is being done though Cambridge appears to be very much a centre for some forms of gene testing.

Rod

[Hidden]

What happens to your Free T4 and free T3 levels on that dose? Does your FT4 rise? If it rises, but the FT3 level doesn't, then you've almost certainly got a conversion problem. Alternatively, it could still be lack of vitamin D. 1600iu isn't a particularly high dose - most people need double that amount to maintain their levels (if they're prone to being deficient) and to increase those levels need 5000iu a day. And you need vitamin D so that T3 can be used at a cellular level. You could throw all the T4 in the world into your system but if your cells can't use it...

A couple of other thoughts:

Have your parathyroids ever been tested?

Has your pituitary function ever been tested (ever had a head injury or whiplash)?

What's your vitamin B12 status? Ferritin levels?

[Phlogiston in reply to Hidden]

Since it's taking months to get a test appointment at GPs (despite them calling me in), I'll have to wait til mid-July to see what the high dose does to my levels. I'll probably then try a course of T3 at higher doses than previously and see how it works. Vit D supplement was 5000U (at my request - Endo prescibed only 1000), but GPs bosses dropped it to 1600U to meet some guidelines. December test said level was OK, but I could easily increase the dose and see if it makes the T4 any more effective. I'll ask for B12 and ferritin levels to be checked at next tests, although I've never been diagnosed with pernicious anaemia despite having been treated for many years in the past for low iron anaemia when vegan.

No doc has ever suggested parathyroid or pituitary might need testing, but haven't had any head injuries. Certainly something to think about in future though if all else fails to help.

[gabkad]

Phlogiston, I've been taking (prescribed) dextroamphetamine for 9 years. It helps. Just 5 mg two or three times per day. It's my 'coffee'. Gives me focus because chronic pain takes it away and I can't take narcs at work. It's probably easier to get ritalin or time release ritalin. I opted for the dex after researching the stimulants. It's smooth and doesn't stimulate the heart or make me jumpy. Ritalin is a bit coarse. Caffeine gives me 'brain fog'. Seems it's some sort of paradoxical response.

Apnea doesn't mean that hypopnea isn't happening and this is in some ways worse. It prevents deep sleep, therefore non-restorative. There can be anatomical reasons for this not just thyroid related. The sleep specialists rarely treat hypopnea.

My sleep study indicated severely fragmented sleep but this was pain related. No apnea. I've been taking zopiclone for 14 years. It stops the pain because it works as a muscle relaxant. The only thing that works for me. I must admit though, Cytomel taken at bedtime has improved my sleep. I feel refreshed in the morning like 20 years ago.

Is there a possibility that you don't absorb the thyroid meds for some reason?

[Phlogiston in reply to gabkad]

Wow - I did ask my GP about amphetamines, half in jest. I think he thought he wouldn't be allowed to prescribe them without a lot of hassle. Modafinil should supposedly have the same effects without the addiction and jumpiness, and it does help a bit but the extreme tiredness at the end of a run is crippling - the doc says many of her patients use it during the week and sleep all weekend which is how I used to function at a high level pre-child. But that's impossible with an active 8 year-old. Not sure that I want Ritalin - actually, Adderall sounds like what I want, but apparently not licenced for UK. Unlike you, caffeine doesn't give me brain fog - it's a little stimulating. Perhaps my sleep requirement isn't thyroid related but I definitely want to try everything until I can rule in out. Many thanks for your input.

[traceytired]

I have no thyroid, and was unable to tolerate 175mcg Thyroxine. Brain fog, painful joints, funny thoughts going on in my head, visual disturbances, migraines etc. Dose was reduced to 100 mcg, and 25mcg T3 added...resulting in a much more stable me!!

Brain fog and visual disturbances have gone. Joints and muscles are much less painful. I felt poisoned on T4 only.

[Phlogiston in reply to traceytired]

Thanks for your response. I have often wondered what happens if thyroid removed, but clearly it doesn't make things easier. The thing with me is not that T4 makes me feel worse, it just doesn't make me feel significantly better as I increase the dose. The various strains of advice all seem to point towards T3, which didn't seem to provide any advantage previously, but I'll push to have another go with that at a higher dose as my next step. Then try NDT if that doesn't improve things.

[waveylines]

Hi Phlogiston -have you read Paul Robinson's book 'Living with T3'? I believe Thyroid Uk have it in their loan library -you might fins it a really useful resource =he too didn't find thyroxine helpful and in the end went across to taking T3 on it's own with the helpful support of a GP. He takes his T3 in staggered doses through the day. He also looked carefully at his vitamins and minerals. he also has a website: recoveringwitht3.com/

[Phlogiston in reply to waveylines]

very interesting - thank you. I see he recommends it for people with low cortisol. So, another thing to think about...

[Phlogiston]

Many thanks for this and for the document which is incredibly useful. Whether or not it is a genetic problem, I'll take a heuristic approach to explore whether this could be the problem.

[Phlogiston]

Tahnks for your response - resistance seems to be a theme, so I'll start by assuming that's what's wrong and try to treat that first.

When I tried T3 previously, there was no difference to T4 (thus I thought my issue isn't a simple lack of conversion) but I might ask GP to try it again on a higher dose and see how that goes, from seeing other material about it on this site. Additionally will try NDT at some point. I'll also ask to have folate and ferritin (and as many other things as they'll do) checked at next tests and see how they look.