Thyroid gland hormones and thyroid function tests in ME/CFS: MEA website poll (April 2017)

[Wishful]

I'd like to see more information about T2 and its effect on CFS. My TSH is elevated and I have the antibodies, but I don't show the normal symptoms of hypothyroidism (my preferred room temperature is 12C) and I don't notice any effects from supplemental T4 or T3. I do get a reduction in symptoms from T2 (3-5 diiodothyronine) or iodine. I think that my elevated TSH is due to neuroinflammation, which is supposed to raise TSH.

I'd make more effort to get another TSH and free T4 test if my experience with doctors wasn't that they only considered standard thyroid disorders and refused to consider other possibilities even when shown research papers offering other possibilities.

 

[charles shepherd]

Yes - the answer should be based on thyroid function test results prior to starting any treatment for a thyroid disorder

I think it will be helpful (if we can do this within the word count for the question) to add ..and prior to any treatment being started...

Question has now been amended:

What was the result of your most recent blood test, or before treatment was given, to assess thyroid gland function?

 

[charles shepherd]

I'd like to see more information about T2 and its effect on CFS. My TSH is elevated and I have the antibodies, but I don't show the normal symptoms of hypothyroidism (my preferred room temperature is 12C) and I don't notice any effects from supplemental T4 or T3. I do get a reduction in symptoms from T2 (3-5 diiodothyronine) or iodine. I think that my elevated TSH is due to neuroinflammation, which is supposed to raise TSH.

I'd make more effort to get another TSH and free T4 test if my experience with doctors wasn't that they only considered standard thyroid disorders and refused to consider other possibilities even when shown research papers offering other possibilities.

There isn't much information in the UK medical and scientific literature about T2

So, in our current state of knowledge, I think this is an approach that needs to be followed with great caution - especially in relation to the fact that if its thyromimetic effects extend to many organs, there is a significant possibility that T2 administration may result in long-term undesirable effects.

This is the most recent review I can find right now:

CS

3,5-Diiodo-L-Thyronine (T2) in Dietary Supplements: What Are the Physiological Effects?
https://doi.org/10.1210/en.2014-1933
Published:
01 January 2015

The high prevalence of obesity in developed and emerging countries is a serious health concern. Its consequences include a significant decrease in the quality of life and life expectancy of affected individuals, not to mention the stress it places on health care delivery systems that must treat the multiple comorbidities associated with it. There is little doubt that we need to reduce our girth for the sake of our health. In addition, the desire to reduce body fat is increasingly driven by esthetic concerns, as evidenced by the growing emphasis on fitness and body building.

• 
  Given the well-known metabolic effects of thyroid hormones (THs) (1), it is not surprising that a TH metabolite, 3,5-diiodo-L-thyronine (T2), has found its way into the formulations of a number of dietary supplements that claim to decrease body fat. They are available “over the counter,” and a quick internet search reveals that they are offered for sale using marketing verbiage such as “fat burner,” “appetite suppressant and fast fat annihilator,” “metabolic accelerator,” etc. Accompanying information may include inaccurate statements, such as “… T2 is a supplement designed to stimulate the thyroid gland,” and it does not always disclose appropriate warnings about potential side effects, nor provide precise directions about the total daily dose that is safe to use. The T2 content per pill may vary significantly among different supplements (50–300 μg), and in some cases, it is not explicitly stated. Oftentimes, T2 is combined with other compounds with complementary or overlapping biological effects, making it difficult to discern which of the metabolic outcomes is the specific result of T2 action. In these circumstances, there is significant risk of untoward effects.
  
  The use of T2 by humans as a metabolism inducer stems from initial findings by Horst et al (2) and Lanni et al (3), who observed that T2 rapidly induced hepatic oxygen consumption and oxidative capacity. In the last 2 decades, work from Goglia's group and others (reviewed in Refs. 4, 5) expanded on these findings and confirmed T2's effects on mitochondrial function, fat mass, lipid metabolism, and its positive influence on insulin resistance (6), further supporting the case for T2 use to enhance metabolism. A T2 analog, TRC150094, is currently being evaluated for comparable metabolic effects (7). T2 has an affinity for the thyroid receptor that is roughly 2 orders of magnitude lower than that of the most active TH, T3. However, the results about T2's relative affinity may vary depending on the biochemical or physiological assay used (8) and be influenced by the purity of the T2preparation. Given its lower affinity for the TH receptors, most of the beneficial effects of T2 on metabolism reported to date have resulted from doses that were significantly higher than the dose of T3 that would be required for the same effect. However, except for its capability to suppress the hypothalamic-pituitary-thyroid (HPT) axis (9, 10), little has been reported regarding any undesirable thyromimetic effects of T2.
  
  Although the ability of T2 to increase metabolism is not in doubt, it is not evident from the published studies what conditions allow for its safe and effective use in humans. This is due in part to the lack of comprehensive human studies, but it is also the result of the fragmented information available in the literature. Published studies often focus on different biochemical or physiological endpoints while using different experimental designs, models, and T2 doses. There is also a considerable bias in the literature towards the beneficial effects of T2, leaving its potential deleterious consequences insufficiently explored. If we consider that its thyromimetic effects may extend to many organs, there is a significant possibility that T2 administration may result in long-term undesirable effects.
  
  In one of the most complete studies available, published in the current issue of Endocrinology (11), Wenke Jonas and investigators in the laboratories of Joseph Kohrle and Annette Schurmann used a mouse model of obesity to analyze the physiological effects of T2. In their thoughtfully designed, carefully performed, and thoroughly discussed experiment, the authors treated obese mice for 2 and 4 weeks with 2 different daily doses of T2 or with a supraphysiological dose of T3 and measured a number of metabolic and physiological endpoints during and after the treatment.
  
  The higher dose of T2 used was 80 times that of T3. Thus, it allows for its estimated lower affinity for the TH receptors, assuming that the affinity of T3for the receptors is indeed 100 times that of T2 (8). This high dose of T2essentially mimicked all the physiological effects obtained with the T3 dose. These effects included suppression of the HPT axis, decreases in fat mass, serum leptin and cholesterol, and increases in lean mass, food intake, and hepatic expression of TH-dependent genes relevant to lipid metabolism (see summary of results in Table 1). After 4 weeks, this high dose of T2 also caused cardiac hypertrophy and resulted in elevated metabolic rate and body temperature. These results demonstrate that at a dose that corrects for its decreased affinity for the TH receptor, T2 is capable of producing the same biological effects as T3.
  
  Table 1
  Summary of the Effects Observed by Jonas et al (11) in T2-Treated Obese Male Mice vs Untreated Controls
  
  Treatment Dose (μg/g BW) Serum T4 Serum T3 TSHb mRNA Body Weight Lean Mass Fat Mass Liver Gene Expression Food Intake Total Cholesterol Heart Weight Energy Expenditure
  T2 0.25 ↓↓ ↓ ↓ ↔ ↔ ↔ ↔ ↔ ↔ ND ND
  T2 2.5 ↓↓ ↓↓ ↓↓ ↔ ↑ ↓ ↑ ↑ ↓ ↑ ↑
  T3 0.03 ↓↓ ↔ ↓↓ ↔ ↑ ↓ ↑ ↑ ↓ ND ND
  BW, body weight; ND, not determined.
  
  At the lower dose, however, the authors found that T2 did not reduce body weight, cholesterol, or fat mass. Nor it did change hepatic gene expression profiles. However, this low dose of T2 exerted a profound effect on the HPT axis, resulting in a marked reduction in the serum levels of T4 and T3, and a significant decrease in the pituitary expression of the TSH β-subunit. These results suggest a preferential effect of T2 on the HPT axis, and this occurs at least at the pituitary level.
  
  There is still limited information about the mechanisms of action of T2. Although alternative molecular pathways cannot be excluded, based on present evidence, it is likely that T2 uses at least some of the same mechanisms, as does endogenous T3. Identifying the cell membrane transporters preferentially used by T2 and determining whether at some dose levels it can interfere with the function of the deiodinases or other proteins that bind TH will be most informative. Recent studies in a fish model (12) suggest that T2 can act as a ligand of the β-isoforms of the TH receptor. This could explain the effects of T2 on pituitary and liver, whose TH-dependent physiologies occur by signaling through that receptor isoform. However, the cardiac hypertrophy observed by the authors at higher doses suggests that T2can also use the α1 receptor, the most abundant in this tissue.
  
  Every tissue features its own complement of transporters, deiodinases, receptors, and associated proteins. They are responsible for modulating TH availability and action in an appropriate, tissue-specific manner. As a result, TH signaling in particular tissues or developmental stages may be largely different from what one would predict based on circulating levels of TH. This complexity in the tissue-specific regulation of TH action provides opportunities for thyromimetic compounds with particular molecular properties to act in a tissue specific fashion when administered appropriately (13, 14).
  
  In this regard, a case could be made for the therapeutic use of T2 in a manner that discriminates between desirable and undesirable effects, especially if we consider its apparent tendency to accumulate in the liver (11) or if there are differences in transport, degradation, and receptor affinity in target tissues not yet identified. But given the pleiotropic effects of TH and the results from Jonas et al (11), more comprehensive studies in humans and animal models are clearly needed to fully evaluate any potential risks. The chronic effects of T2 on important organs that are targeted by TH (eg, pituitary, heart, brain, bone, muscle) have not been sufficiently investigated, and it is possible that differences among species, methods of T2 administration and overall experimental design may lead to inconsistent results. In addition, further molecular research aimed at clearly defining the mechanisms of action of T2and its interactions with other determinants of TH availability and signaling will also be of benefit.
  
  In the meantime, the current literature and the results presented by Jonas et al (11) indicate that, in addition to increased metabolism and reduced fat mass, T2 administration also leads to suppression of the HPT axis, increased food intake, and cardiac hypertrophy. A particular point of concern is the observation that the lower dose of T2 used by the authors exerts negligible effects on adiposity and metabolic outcomes, yet results in a marked suppression of the HPT axis leading to reduced levels of circulating T4 and T3(and presumably TSH), with unknown long-term consequences. The implication of this finding is that, for a given dose, the detrimental effects of T2 on the HPT axis may preferentially occur before the intended metabolic ones. Thus, for the time being, these new data should compel users of T2-containing supplements to assess their thyroid status, err on the side of caution, and limit their daily dose, as appropriate.
  

 

[charles shepherd]

Re prescribing T3 products:

This is the sort of guidance that UK doctors are given on the prescribing of T3

The information below comes from my local health authority/clinical commissioning group and Glos Hospital endocrinologists

Guidance on the Prescribing of Liothyronine (T3) Containing Products for the Management of Primary Hypothyroidism

http://www.formulary.glos.nhs.uk/PageFiles/216/Liothyronine guidance.pdf

Dr Charles Shepherd
Hon Medical Adviser, MEA

 

[charles shepherd]

From one of our members taking part in a parallel discussion on the MEA website:

"On the question of thyroid disorder, it appears to be well documented that the reference ranges used in UK are somewhat lower than other countries.

Why are we not testing properly and why is T3 so expensive when cheap to make. I understand that only one pharmaceutical company manufactures it here. Why is that?

People have been taking treatment into their own hands which is a difficult road to plot. But who can blame them when the medical profession is so intransigent about proper testing of individuals; what may be one person’s reference range may not be another’s.

There has been ongoing debate in the Scottish Parliament."

Reply from Tony Britton:

I’ve just found an interesting YouTube of a discussion on the subject at the Scottish Parliament’s petitions committee on 5 February 2016.

Sandra Whyte, Marian Dyer and Lorraine Cleaver are presenting their petition: “Effective Thyroid and Adrenal Testing, Diagnosis and Treatment”.

 

[Wishful]

My wish for more information about T2's effects wasn't really a request for papers (though I appreciate the one you posted); it was more of a wish that researchers would investigate more. T2 seems to have significant effects in the body, so it shouldn't be ignored. I guess it's a matter of funding: funding goes to whatever is fashionable at the time, and little-known processes just aren't fashionable...and aren't likely to be until someone does do research and finds something interesting.

 

[dangermouse]

Had appointment at surgery (they asked me to go in to discuss an email that I'd sent about OI symptoms worsening. I simply wanted them to ask my cardiologist about my Ranolazine and if it could be causing side effects that impact OI).

Had to see Nurse as my GP fully booked up. I'll make sure I see my GP in future as he knows me well. The nurse will write to cardiologist re OI symptoms. She arranged for my thyroid test and Serum Ferritin (as I'd told her I have a history of both being low) and she's doing vitamin D. That was good.

What wasn't so good was her promoting the local CFS clinic to me. I had struggled in (my husband took me) and had little energy. I then had to explain that I've attended one already and explained all that I do myself to help myself and that my Dr doesn't think there's anything they can tell me that I haven't already tried. Also, he understands how much effort it takes to attend any referrals.

I won't be making the mistake of seeing the nurse again. I'm hoping that I'll not need to go in again any time soon. If I do I'll wait however long I need to in order to see my Dr.