Thyroid Megathread

[Learner1]

This shows a relationship between thyroid and pyruvate dehydrogenase, which is the thing found to be impaired in Fluge and mella's study

This is what Fluge and Mella's study says...they have NO mention at all of thyroid:

PDH functions as a gateway in oxidative metabolism by coordinating the breakdown of 2- and 3-carbon energy substrates derived from carbohydrates, fats, and amino acids (18). A reduction in PDH enzymatic activity may lead to accumulation of pyruvate and thereby cause overproduction of lactate, even in the presence of adequate oxygen levels (16). In addition to allosteric regulation, PDH activity is controlled by PDH kinases (PDKs) that inhibit PDH enzyme activity by phosphorylation (19, 20) and PDH phosphatases that catalyze reciprocal dephosphorylation (18).

Sirtuin 4 (SIRT4) was recently identified as a mitochondrial lipoamidase inhibiting PDH activity (21). PDK1–PDK4 are regulated at the transcriptional level via signaling cues involving factors such as AMP-dependent protein kinase (AMPK) (22), PPARs
(23), and HIF1 (24).

A possible role of impaired PDH function and abnormal AMPK activation in ME/CFS has been proposed (25).In summary, previous findings support that PDH dysregulation and changes in serum amino acids may be involved in the pathomechanism of ME/CFS.

We hypothesized that ME/CFS is associated
with defective oxidative metabolism involving PDH, leading to increased utilization of ketogenic amino acids to fuel the TCA cycle.

 

[frozenborderline]

This is what Fluge and Mella's study says...they have NO mention at all of thyroid:

I'm not saying what fluge and mella's conclusion was, but I'm just pointing out that thyroid hormones affect both pyruvate dehydrogenase and pyruvate dehydrogenase kinase. There are many possible pieces to this puzzle

I don't see why they would need to mention thyroid for thyroid to possibly be relevant--the scope of their study was limited. Again, I'm certainly not drawing any firm conclusions, but there are possible connections here.

 

[Learner1]

Yes there are.

And, as someone who is on a lot of T3, T4, iodine and selenium, and still has a PDH block, and is sucking up amino acids like there's no tomorrow, my experience is that no matter what you do with your thyroid it won't cure this disease.

There are MANY other things going on in the immune, digestive and nervous systems, the adrenals and the rest of the endocrine system.

Finding a dosing of T2, T3, T4, NDT, iodine and selenium that optimizes one's function is a very worthwhile foundation for heading down a pathway to a cure.

But, as has been said by many, you're not going to get the thyroid working properly if the adrenals aren't working. Then you have to look at why the adrenals are off, which is typically from some sort of stressor - toxin, infection, EMF, emotional stress, etc. and deal with that.

Getting one's immune system working properly, beating back infections, resolving autoimmunity, caring for the vagus nerve, restoring the microbiome, resolving nutrient deficiencies and imbalances, getting rid of mercury, arsenic, BPA, glyphosate, mycotoxins, etc., are all pieces of the puzzle, which will vary somewhat from patient to patient.

 

[pattismith]

But, as has been said by many, you're not going to get the thyroid working properly if the adrenals aren't working.

you are right: it took me some more months to experiment it, but I can say now that the non genomic action of T3 only works for me if cortisol level is sufficient, and vice versa.

The conjugated non genomic effect of T3 and cortisol may be on intracellular Ca, but I have to investigate it further

 

[Misfit Toy]

is post exertional malaise a symptom of hypothyroidism? I have read that it is. If that's the case, there is a huge overlap with CFS.

Actually, it is. Many people who are hypothyroid talk about how when they do something that is strenuous, they do not bounce back. This is not everyone but many and especially among the thyroidless community.

It depends on the severity of the hypothyroidism. Some are only on 50 mcg of T4. Some are on 150 mcg. It all depends. It also depends because hypothyroidism has so many variables and issues including reverse T3 problems which can make people feel lifeless or anxious.

 

[Misfit Toy]

But, as has been said by many, you're not going to get the thyroid working properly if the adrenals aren't working. Then you have to look at why the adrenals are off, which is typically from some sort of stressor - toxin, infection, EMF, emotional stress, etc. and deal with that.

Fact. I am supposedly doing well thyroid wise and yet I feel like death. Why? Adrenals, MCAS and a million other things. All of which I can't even keep up with anymore.

This thing is way bigger than I can keep up with, nor have I been able to for 30 years. It, to me, is never-ending. One thing seems to be fixed only to have another go awry.

Again, whack-a-mole syndrome. WTF syndrome.

 

[Learner1]

I agree. But we have to keep trying. Hang in there....

 

[drob31]

Fact. I am supposedly doing well thyroid wise and yet I feel like death. Why? Adrenals, MCAS and a million other things. All of which I can't even keep up with anymore.

This thing is way bigger than I can keep up with, nor have I been able to for 30 years. It, to me, is never-ending. One thing seems to be fixed only to have another go awry.

Again, whack-a-mole syndrome. WTF syndrome.

Have you ever tried black seed oil?

 

[Misfit Toy]

Have you ever tried black seed oil?

No. I have never heard of it.

 

[percyval577]

My interpretation of the discussion (in my way):


- Our disease me/cfs affects more women, with about 75% I think it was.

- "After seven weeks, the thyroids obtained from treated female mice were enlarged, while those from male mice did not become goitrous." effects of manganese on thyroid hormone homeostasis


Tell me it wouldn´t be interesting.


I feel very sorry for you @Misfit Toy. The whole thing is such complex (anyway) and would interact with different personalities, ie genes and history. Btw, I too underwent a supposal by a doctor, this when I was especially bad with thinking. I was "interested in" despite I knew it better. Probably my soul only wanted to have some answere. It´s rather a shame (but not for you) to say, stay away from doctors. - Keep up your bright sight. -

 

[ahmo]

My thyroid stopped working in adolescence. I was on initially thyroid glandular, then thyroxine for decades. Some years into ME/CFS it was clear my rT3 was high. I tried a variety of combinations of natural thyroid, T3, T4. None of them worked.Eventually I discovered John Lowe and followed his recommendations for T3 only. It's been a boon, also not monitoring by blood test results, but by symptoms. I now see I was always under-medicated when on thyroxine. But thyroid has not had any effect on the underlying ME.

 

[drob31]

No. I have never heard of it.

Ok, it's something I came across recently. I'm also having thyroid/adrenal issues that I can't seem to wrangle.

Blackseed (thymoquinone) oil has powerful effects against autoimmune triggered hypothyrodism, and against many pathogens like ebv/hhv6. Might be worth looking in to.

 

[JBoneske]

How do you know if you are having adrenal issues? Cortisol tests? I had a slightly elevated morning cortisol test at the beginning of trying to find out why I as sick.
Did the ACTH test. Came back normal. 24 hour urine came back at top of range. 11pm saliva tests came back normal too.
So is adrenal function determined by cortisol levels?

 

[drob31]

How do you know if you are having adrenal issues? Cortisol tests? I had a slightly elevated morning cortisol test at the beginning of trying to find out why I as sick.
Did the ACTH test. Came back normal. 24 hour urine came back at top of range. 11pm saliva tests came back normal too.
So is adrenal function determined by cortisol levels?

They are both connected.

Lately I'm convinced that thyroid issues can cause hpa-axis dysfunction. I think it works the other way as well.

 

[ljimbo423]

I don't know if this has been posted here yet but I found it really interesting.....

CONCLUSION:
The present study suggests that a clinically helpful TSH cut-off value for hypothyroidism should be based on associated symptoms, not just in population studies.

Based on the assessment of depression, our study concludes that a TSH cutofff value of 2.5 MIU/L is optimal.

LINK

Jim

 

[drob31]

I don't know if this has been posted here yet but I found it really interesting.....

LINK

Jim

Yeah, from what I've been reading lately, the TSH doesn't matter at all in regards to "should you treat someone."

You actually want TSH to be produced because it activates dieodinases in peripherial tissues.

If you take high dose t3, it likely won't even make it to the peripherial tissues and lower your TSH.

Most people need mostly t4 and a little t3. You also need to produce TSH while you are taking it, so basically you need to start very low and go slow with thyroid hormone.

 

[pattismith]

“Pyruvate dehydrogenase complex activity was unchanged in the hyperthyroid state but was significantly reduced (by a third) in hypothyroid rats.”

https://www.ncbi.nlm.nih.gov/pubmed/489548


This shows a relationship between thyroid and pyruvate dehydrogenase, which is the thing found to be impaired in Fluge and mella's study

The link could be a decrease in intracellular calcium or mitochondrial calcium

-T3 increases intracellular cytoplasmic calcium
-Decrease in intramitochondrial calcium inhibits pyruvate dehydrogenase

"Thus, the stimulation of metabolic flux through the reaction catalyzed by the pyruvate dehydrogenase complex appears to result from an increase in intramitochondrial [Ca(2+)] ions in astrocytes. Such a mechanism for stimulation of the same enzyme has been convincingly demonstrated in other cell types"

 

[learning]

An article from 2007, about changes in serum levels and maybe directly on thyroidal actions (deiodinase) by manganese.

According to the question of #8 one might boldly guess manganese (of course not part of #8) might be
A) the same root-cause under different circumstances with two different diseases (cf ~2.1.in #10), or
B) the same cause with only different effects in order to one systemic goal and then disease (cf -2.2.in #10). However:​

effects of manganese on thyroid hormone homostasis

3a:
"We posit that manganese may affect thyroid hormone homeostasis and neurodevelopmental processes as a result of both direct dysregulation at the level of the thyroid gland and thyroid hormones, or indirectly via alterations in dopaminergic control of the thyroid gland and its hormones. Dopamine is a known modulator of both TSH and TSH subunit secretion. ...

Abstract
"Dopamine is also a known inhibitory modulator of thyroid stimulating hormone (TSH) secretion.The involvement of dopamine and dopaminergic receptors in neurodevelopment, as well as TSH modulation, led us to hypothesize that excessive manganese exposure may lead to adverse neurodevelopmental outcomes due to the disruption of thyroid homeostasis via the loss of dopaminergic control of TSH regulation of thyroid hormones. This disruption may alter thyroid hormone levels, resulting in some of the deficits associated with gestational exposure to manganese."

3a
"An additional effect of manganese on thyroid hormones homeostasis may be mediated through their metabolizing enzymes. Current data suggests that manganese can affect thyroid hormones directly by regulating the deiodinase enzymes. ...

To examine the effect of manganese on the regulation of thyroid hormone, rats were treated with a manganese-rich diet (10 mg/kg/day as manganese sulfate [MnSO4]) for a period of five weeks (Buthieau and Autissier, 1983). High accumulation of manganese in the pituitary gland resulted in a significant decrease in serum T4, T3, and in TSH concentrations. No change in thyroidal T4 and T3 concentrations were observed. Given that binding of TSH to thyroid plasma membranes is strongly inhibited by neutral salts at relatively low concentrations, manganese probably contributes to a decrease in the binding of TSH to the thyroidal plasma membrane. The decrease in binding would then result in higher circulating TSH levels which, through negative feedback, would inhibit release of TSH from the pituitary gland. It is expected that the decrease in T4 levels would be followed by an enhanced pituitary TSH secretion. In agreement with other studies this study suggests that the role of manganese in thyroid hormone regulation and metabolism is not directly mediated by thyroid hormone synthesis."

(+) salt (eg Mn) -> (-)TSH at thyroid plasma membrane ->
(+) TSH in serum -> inhibition of TSH release from pituitary gland ->
(-) TSH in serum

But no change of T4/3 in the thyroid gland​

Conclusion
"Many questions still remain concerning the relationship between manganese and thyroid hormones. Although not conclusive, experimental findings point to the ability of manganese to interfere with deiodinase activity thus affecting circulating thyroid hormone concentrations. The role of manganese uptake by the thyroid gland is still unclear and the potential mechanisms by which it may directly affect thyroid hormone homeostasis or function remain to be elucidated; however, dose-dependent goitrogenic effects of manganese have been illustrated. It is also noteworthy, that effects of manganese on optimal brain dopamine concentrations, which in turn, affect thyroid hormone homeostasis, may alter the regulatory function of thyroid hormone, both in developing and mature animals. Similarly, manganese may affect a plethora of other neurotransmitters, in turn, causing dysregulation of thyroid hormone homeostasis."

referring to #3/10, analogous to insulin. Effects of Mn on the thyroidal system:

type 1 (altering of the gland) -- possibly deiodinase: D1 (responsible for 20% of complete T3)
type x (altering of the blood levels) -- yes (1983), practical importance? as Mn may be only part of some salt.
type 2 (altering of the target cells) -- possibly deiodinase: D1 (liver,kidney), D2 (brain,other), D3 (inactivation)
type 3 (altering indirectly) -- via dopamine which inhibits TSH secretion

There is an action of Mn via upregulating gene expression of inducible nitric oxide synthase.
The amounts of nitric oxide are shown to reuptakeinhibit dopamine (with some chaos?...)

This dopamine is as well a possible common between the diseases cf (3/4)#10.
The non-thyroid action would be directly some altering of the feeling and further interdependencies with other nerves.​

I'm trying to make sense of all this... basically manganese has an effect on thyroid function but it is not well understood. thyroid needs manganese to function but too much manganese causes thyroid problems?

 

[Wishful]

It sounds like the researchers didn't come up with a clear conclusion, but wrote it up anyway for whatever benefits they might get. I noted that they're talking about gestational intake and neurodevelopment (momma's Mn intake affecting babies) and were trying (and failing to do directly) to prove that Mn affects thyroid hormones which in turn affects baby brain development. It seems to me that there are too many other possible factors and pathways involved.
I had mildly elevated serum Mn during one part of my ME, and later followed a low-Mn diet, and didn't notice any difference in symptoms, so I don't believe there's a significant link between Mn and ME, at least not for me.

 

[learning]

It sounds like the researchers didn't come up with a clear conclusion, but wrote it up anyway for whatever benefits they might get. I noted that they're talking about gestational intake and neurodevelopment (momma's Mn intake affecting babies) and were trying (and failing to do directly) to prove that Mn affects thyroid hormones which in turn affects baby brain development. It seems to me that there are too many other possible factors and pathways involved.
I had mildly elevated serum Mn during one part of my ME, and later followed a low-Mn diet, and didn't notice any difference in symptoms, so I don't believe there's a significant link between Mn and ME, at least not for me.

This sounds right to me, but then what is dopamine's role in it?