[Epistemic status: speculative. Definitely don’t try to make a decision based on this without speaking to an endocrinologist first.]
So, let me see if I understand what you wrote, adding in a few things I read on Wikipedia and the interpretations that seem obvious to me.
T3 controls metabolic rate, by upregulating metabolic processes throughout the body. TSH controls the concentration of T3 by setting the rate at which T4 is converted to T3. TSH is tested for, T3 and T4 are usually not. The Wikipedia page for TSH lists diagnoses for the cross-product of T3 and TSH, with primary hyper- and hypothyroidism corresponding to the cases where they are mismatched: high TSH and low T3, or low TSH and high T3. Cases where T3 and TSH are both low indicate iodine deficiency, because iodine is also a necessary part of the conversion from T4 to T3. TSH is linked to the circadian rhythm.
Adding a bit of interpretation of my own, TSH represents the difference between the body’s overall metabolic rate is, and what some mechanism thinks it should be. Under this model, symptoms of metabolic-rate-too-low would appear if:
That unspecified mechanism were disrupted such that TSH was targeting a level of activity that was too low
There is an unaccounted energy sink which the thyroid system can’t detect/compensate for
The circadian rhythm was disrupted in such a way that TSH was inconsistent from day to day
(All diabetics with imperfect blood sugar control would fall in the “unaccounted energy sink” category. I have T1DM. fibromyalgics probably would too; the characteristic symptom of fibromyalgia is chronic pain of undiagnosed origin, and chronic pain is very likely to have a corresponding ongoing energy expenditure.)
At this point the selection of possible causes has fanned out enough that it seems implausible for everyone with CFS symptoms to have the same root cause. But it’s also the case that, under this model, T3 supplementation is likely to help with a broader range of causes than TSH is.
However, there are two good reasons to hesitate before trying a T3 supplement such as pig thyroid. First: this is bypassing several feedback/regulatory steps in the body, so there’s a much higher risk of accidentally overshooting and getting a dangerous overdose. And, second: increasing overall availability of energy in the body can make infections and cancers worse.
I think you’ve essentially got the standard picture, except that TSH is thought to be the thing controlling T4/T3 production. There are those that say that it also controls T4->T3 conversion.
This paper:
Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment
Rudolf Hoermann, John E. M. Midgley, Rolf Larisch and Johannes W. Dietrich
Suggests that it’s all a bit more complicated than that though.
And I’d imagine that high TSH might make your thyroid swell, or what are goiters? Apparently goiters and cretinism used to be anticorrelated in areas where both were popular.
I’m certainly not suggesting that anyone with CFS should start snorting pig thyroid! I think that’s just sticking a screwdriver in a complicated control mechanism. You might well provoke a response.....
I am saying that CFS/FMS/hypothyroidism look far too similar for it to be a coincidence, two different diseases with the exact same symptoms apart from TSH, and that CFS may well be related to some aspect of disturbed metabolic rate-control. And that I don’t think that the normal TSH of CFS sufferers is enough to prove that CFS is something else entirely.
And obviously, I wonder if pig-thyroid might not be a bad screwdriver to stick in. And I’m puzzled that no-one’s tried it in a PCRT. There are occasional papers where someone’s given T4 alone to tired people (well, I’ve read one). That doesn’t seem to work, or at least if it did work on a couple of them it wasn’t enough of them to make a statistically significant difference to the group as a whole.
And there are other papers where people have given T4/T3 mixes to hypothyroid cases. There was a famous one where it measurably worked, and lots of attempts to replicate it with slightly different cocktails that didn’t. And of course, scientific statistics being what it is that’s gone down as 1 vote for, 7 votes against, so the initial interest has died down. I think it’s pretty solid that some patients prefer various T4/T3 mixes, it’s just that no-one cares.
I think actually just trying random things is doomed to fail, and what’s necessary is to work out what’s going on and what’s likely to work.
My money would be on T4 plus a tiny bit of T3 being the ideal solution for a large subclass of CFS sufferers whose metabolism is running slow. But I have no clue.
Buskila, Sarzi-Puttini and Ablin in their paper The genetics of fibromyalgia syndrome (Pharmacogenomics, 8(1) 67-74) say it is probably polygenic, so perhaps there is significant overlap in the genes making people more likely to get either of the disorders. (I only read the abstract.)
Damn, I can only see the abstract. I’d like to see that paper if anyone has a copy.
They seem to be fingering endocrine genes, but adrenal rather than thyroid. A lot of alternative medicine people talk about ‘adrenal fatigue’ in this context, but I hadn’t been paying much attention to that since ‘real’ doctors don’t think it’s a thing.
But I don’t know what I’m talking about! Can anyone who does read that paper and tell us what it means?
Meh, I don’t think you are wrong, I just think you will have to incorporate genome sequencing in recommendations for future research (even if you won’t conduct it yourself). Maybe some of the genes they found should go into the confounder bin?.. And of course, they mention ‘additional comorbid conditions’ (cretinism?), so it will be a very convoluted question. Not to mention that you should also look up any studies on 1) whether pig-thyroid-eating people had better or worse outcomes when compared to what is expected from an equivalent dose of pure hormones, and 2) what substances are found in the preparation (preferably something with mass-spectrometry as the method ofidentification) & how it was made (I don’t know a thing about pigs, but they do have parathyroid glands—could those be included, too?), 3) how well do the respective forms of hormone store (under such freeze-drying conditions) - I bet that they decompose at different rates, which means… I can’t even say what it wouldean right now, except that standardization of doses should be difficult.
1) Can’t find any data on this. 1970s experiments concluded pig-thyroid much worse than pure T4, but they were using very large doses of T4, and when they swapped some of it for T3, it might have over-ridden the conversion mechanism and produced hyper symptoms. Also I suspect that only a small number (ballpark 16% notice, 2% notice strongly) of people would be happier on T4/T3 mix. Also there’s too much T3 in pig-thyroid, it is thought. T3 monotherapy generally believed to be a disaster. And I would suspect that to be right if I didn’t have John Lowe’s posthumous word that it works well for some people including him.
2) I’d love to see that if you know where it might be found.
3) Christ alone knows. One of the original concerns with pig-thyroid was inconsistency. I think they do it better now. Synthetic T4 also has a slightly patchy consistency record, according to some sources.
And, second: increasing overall availability of energy in the body can make infections and cancers worse.
I wonder about this. A lot of things, including cancers, are caused by viruses / may be caused by undiscovered infective agents. If slow metabolism also slows your immune system, then a lot of horrid things might take advantage of that fact.
Cochran said that on genetic load grounds alone, we should expect an awful lot of diseases we currently think are non-infective to be cryptically infective (e.g. ulcers) or recent broken infection defenses (e.g. sickle-cell).
I wonder about this. A lot of things, including cancers, are caused by viruses / may be caused by undiscovered infective agents. If slow metabolism also slows your immune system, then a lot of horrid things might take advantage of that fact.
Not sure if you’re saying this, but to be clear, I don’t think that your suggestion and user:jimrandomh’s are mutually exclusive.
[Epistemic status: speculative. Definitely don’t try to make a decision based on this without speaking to an endocrinologist first.]
So, let me see if I understand what you wrote, adding in a few things I read on Wikipedia and the interpretations that seem obvious to me.
T3 controls metabolic rate, by upregulating metabolic processes throughout the body. TSH controls the concentration of T3 by setting the rate at which T4 is converted to T3. TSH is tested for, T3 and T4 are usually not. The Wikipedia page for TSH lists diagnoses for the cross-product of T3 and TSH, with primary hyper- and hypothyroidism corresponding to the cases where they are mismatched: high TSH and low T3, or low TSH and high T3. Cases where T3 and TSH are both low indicate iodine deficiency, because iodine is also a necessary part of the conversion from T4 to T3. TSH is linked to the circadian rhythm.
Adding a bit of interpretation of my own, TSH represents the difference between the body’s overall metabolic rate is, and what some mechanism thinks it should be. Under this model, symptoms of metabolic-rate-too-low would appear if:
That unspecified mechanism were disrupted such that TSH was targeting a level of activity that was too low
There is an unaccounted energy sink which the thyroid system can’t detect/compensate for
The circadian rhythm was disrupted in such a way that TSH was inconsistent from day to day
(All diabetics with imperfect blood sugar control would fall in the “unaccounted energy sink” category. I have T1DM. fibromyalgics probably would too; the characteristic symptom of fibromyalgia is chronic pain of undiagnosed origin, and chronic pain is very likely to have a corresponding ongoing energy expenditure.)
At this point the selection of possible causes has fanned out enough that it seems implausible for everyone with CFS symptoms to have the same root cause. But it’s also the case that, under this model, T3 supplementation is likely to help with a broader range of causes than TSH is.
However, there are two good reasons to hesitate before trying a T3 supplement such as pig thyroid. First: this is bypassing several feedback/regulatory steps in the body, so there’s a much higher risk of accidentally overshooting and getting a dangerous overdose. And, second: increasing overall availability of energy in the body can make infections and cancers worse.
Jim,
I think you’ve essentially got the standard picture, except that TSH is thought to be the thing controlling T4/T3 production. There are those that say that it also controls T4->T3 conversion.
This paper: Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment Rudolf Hoermann, John E. M. Midgley, Rolf Larisch and Johannes W. Dietrich
Suggests that it’s all a bit more complicated than that though.
And I’d imagine that high TSH might make your thyroid swell, or what are goiters? Apparently goiters and cretinism used to be anticorrelated in areas where both were popular.
I’m certainly not suggesting that anyone with CFS should start snorting pig thyroid! I think that’s just sticking a screwdriver in a complicated control mechanism. You might well provoke a response.....
I am saying that CFS/FMS/hypothyroidism look far too similar for it to be a coincidence, two different diseases with the exact same symptoms apart from TSH, and that CFS may well be related to some aspect of disturbed metabolic rate-control. And that I don’t think that the normal TSH of CFS sufferers is enough to prove that CFS is something else entirely.
And obviously, I wonder if pig-thyroid might not be a bad screwdriver to stick in. And I’m puzzled that no-one’s tried it in a PCRT. There are occasional papers where someone’s given T4 alone to tired people (well, I’ve read one). That doesn’t seem to work, or at least if it did work on a couple of them it wasn’t enough of them to make a statistically significant difference to the group as a whole.
And there are other papers where people have given T4/T3 mixes to hypothyroid cases. There was a famous one where it measurably worked, and lots of attempts to replicate it with slightly different cocktails that didn’t. And of course, scientific statistics being what it is that’s gone down as 1 vote for, 7 votes against, so the initial interest has died down. I think it’s pretty solid that some patients prefer various T4/T3 mixes, it’s just that no-one cares.
I think actually just trying random things is doomed to fail, and what’s necessary is to work out what’s going on and what’s likely to work.
My money would be on T4 plus a tiny bit of T3 being the ideal solution for a large subclass of CFS sufferers whose metabolism is running slow. But I have no clue.
Buskila, Sarzi-Puttini and Ablin in their paper The genetics of fibromyalgia syndrome (Pharmacogenomics, 8(1) 67-74) say it is probably polygenic, so perhaps there is significant overlap in the genes making people more likely to get either of the disorders. (I only read the abstract.)
Damn, I can only see the abstract. I’d like to see that paper if anyone has a copy.
They seem to be fingering endocrine genes, but adrenal rather than thyroid. A lot of alternative medicine people talk about ‘adrenal fatigue’ in this context, but I hadn’t been paying much attention to that since ‘real’ doctors don’t think it’s a thing.
But I don’t know what I’m talking about! Can anyone who does read that paper and tell us what it means?
Both the paper and an update to it can be found quite easily on Library Genesis.
Ooh, that is an interesting site. Thankyou. Paper downloaded and will read.
Thanks, I’ll have a look! Other minds finding reasons why I’m wrong is exactly why I stuck this on Less Wrong. (Also it’s just quite a fun puzzle)
Meh, I don’t think you are wrong, I just think you will have to incorporate genome sequencing in recommendations for future research (even if you won’t conduct it yourself). Maybe some of the genes they found should go into the confounder bin?.. And of course, they mention ‘additional comorbid conditions’ (cretinism?), so it will be a very convoluted question. Not to mention that you should also look up any studies on 1) whether pig-thyroid-eating people had better or worse outcomes when compared to what is expected from an equivalent dose of pure hormones, and 2) what substances are found in the preparation (preferably something with mass-spectrometry as the method ofidentification) & how it was made (I don’t know a thing about pigs, but they do have parathyroid glands—could those be included, too?), 3) how well do the respective forms of hormone store (under such freeze-drying conditions) - I bet that they decompose at different rates, which means… I can’t even say what it wouldean right now, except that standardization of doses should be difficult.
Er, hope that helps.
1) Can’t find any data on this. 1970s experiments concluded pig-thyroid much worse than pure T4, but they were using very large doses of T4, and when they swapped some of it for T3, it might have over-ridden the conversion mechanism and produced hyper symptoms. Also I suspect that only a small number (ballpark 16% notice, 2% notice strongly) of people would be happier on T4/T3 mix. Also there’s too much T3 in pig-thyroid, it is thought. T3 monotherapy generally believed to be a disaster. And I would suspect that to be right if I didn’t have John Lowe’s posthumous word that it works well for some people including him.
2) I’d love to see that if you know where it might be found.
3) Christ alone knows. One of the original concerns with pig-thyroid was inconsistency. I think they do it better now. Synthetic T4 also has a slightly patchy consistency record, according to some sources.
I wonder about this. A lot of things, including cancers, are caused by viruses / may be caused by undiscovered infective agents. If slow metabolism also slows your immune system, then a lot of horrid things might take advantage of that fact.
Cochran said that on genetic load grounds alone, we should expect an awful lot of diseases we currently think are non-infective to be cryptically infective (e.g. ulcers) or recent broken infection defenses (e.g. sickle-cell).
Not sure if you’re saying this, but to be clear, I don’t think that your suggestion and user:jimrandomh’s are mutually exclusive.