T4/T3 combo not found to be better than T4

debored13

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https://www.ncbi.nlm.nih.gov/pubmed/15163340/
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Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism.

Randomized controlled trial
Siegmund W, et al. Clin Endocrinol (Oxf). 2004.
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Abstract

OBJECTIVES: There is evidence from recent controlled clinical studies that replacement therapy of hypothyroidism with T4 in combination with a small amount of T3 may improve the well-being of the patients. As the issue is still the subject of controversial discussion, our study was assigned to confirm the superiority of a physiological combination of thyroid hormones (absorbed molar ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning.
DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4 weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross-over study without washout between the treatment periods was performed in 23 hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of the respective T4 dose was substituted by T3.
MEASUREMENTS: Standard hormonal characteristics and standardized psychological tests to quantify mood and cognitive performance were measured after the run-in period and at the end of each treatment period. In 12 subjects, the concentration-time profiles of fT3 and fT4 were compared after the last administration of the respective study medication. TSH, fT3 and fT4 were measured with immunological assays.
CLINICAL RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except for TSH, which was more suppressed after T4/T3. The efficacy of replacement therapy with the T4/T3 combination was not different from the T4 monotherapy with regard to all psychological test scores describing mood and cognitive functioning of the patients. Mood was even significantly impaired by the T4/T3 combination in eight subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026). PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h)) of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8 +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a history of Graves' disease or autoimmune thyroiditis had significantly higher serum trough levels of fT3 whereas the fT4 concentrations were significantly lower in patients with a nonautoimmune background.
CONCLUSION: Replacement therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive performance compared to the standard T4 monotherapy. There is even a higher risk of signs of subclinical hyperthyroidism associated with impaired well-being of the patients, which is clearly caused by significant fluctuations in the steady-state fT3 serum concentrations.

 
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debored13

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https://www.ncbi.nlm.nih.gov/pubmed/27540557/
Severe TSH Elevation and Pituitary Enlargement After Changing Thyroid Replacement to Compounded T4/T3 Therapy.

Pappy AL 2nd, et al. J Investig Med High Impact Case Rep. 2016 Jul-Sep.
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Abstract

We present the first case of iatrogenic hypothyroidism as a result of compounded thyroid hormone (T4/T3) therapy. The thyroid replacement was changed from 175 µg levothyroxine (LT4) to 57/13.5 µg compounded T4/T3 daily in order to improve the T3 level, despite normal thyroid-stimulating hormone (TSH). This resulted in clinical manifestations of hypothyroidism and high TSH level (150 µIU/mL). Six months later, the patient was referred to our clinic for abnormal pituitary magnetic resonance imaging. On reinitiating a physiologic dose of LT4, clinical and biochemical abnormalities resolved and the pituitary gland size decreased. Our case emphasizes the importance of using TSH level to gauge dose adjustments in primary hypothyroidism. Also, it underscores the current American Thyroid Association recommendation against routine use of compounded thyroid hormone therapy.
 

debored13

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Anecdotally, I have had poor reactions to standard doses of t3, after an initial period of good reactions, so I understand Blanchard’s ideas to be plausible. But from an evolutionary health perspective it’s odd to me that the ideal ratio would be something like his 98:1 ratio rather than the 4:1 ratio found in natural sources. Were the ancestors of ours that used thyroid in fish head and chicken neck soup only using it for short term boosts? Is this why they wouldn’t have experienced the t4 depletion or tsh suppression Blanchard describes happening in standard doses /ratios of desiccated thyroid ?
 

Hip

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My understanding is that it's only a certain small subset of hypothyroid patients that feel better with some T3 added to their T4 medication.

So unless you are testing that specific subset, you will not observe any benefits of adding T3.
 

Helen

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I haven´t read the article, but I suspect it was written by one of the endocrinologist who defends T4 only as a treatment for any obscure reason. Research, and experience has clearly shown that many patients have problem with converting T4 to T3 and therefore need T3 added, or Natural Dessicated Thyroid that contains T4, T3, T2 and T1 as well as calcitonin; all substances that are produced by a healthy thyroid.

Dr. Jeffrey Dach has written excellent articles, with references, on his blog about thyroid diseases and treatment.

https://jeffreydachmd.com/2018/11/paradigm-shift-from-levothyroxine-to-combination-t3-t4-thyroid/

I do recommend reading them as he is a great author on these topics.
 

debored13

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I haven´t read the article, but I suspect it was written by one of the endocrinologist who defends T4 only as a treatment for any obscure reason. Research, and experience has clearly shown that many patients have problem with converting T4 to T3 and therefore need T3 added, or Natural Dessicated Thyroid that contains T4, T3, T2 and T1 as well as calcitonin; all substances that are produced by a healthy thyroid.

Dr. Jeffrey Dach has written excellent articles, with references, on his blog about thyroid diseases and treatment.

https://jeffreydachmd.com/2018/11/paradigm-shift-from-levothyroxine-to-combination-t3-t4-thyroid/

I do recommend reading them as he is a great author on these topics.
I’m aware of the arguments and anecdotes in favor of t3/t4 combinations of various amounts , and have read multiple different thyroid people that are against T4 monotherapy, but I still can’t find any good RCTs that show benefit for t3 /t4 combos. That’s really what I am looking for, or even reviews/meta studies if there are any
 

Learner1

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These studies. are for people with hypothyroidisn, not people with ME/CFS, chronic Epstein Barr, or who are otherwise chronically ill. Antibodies and reverse T3 weren't measured. TG gene status wasn't taken into account. Nor were selenium or iodine status. Or gluten consumption.

We are not widgets. We are unique individuals with individual genes, infections, nutrient status, etc. I have lost faith in any RCT dictating what I'm going to do because I am 100% sure that the people in these RCTs cannot be anything like me.

Now, what problem are we trying to solve here?;)
 

bertiedog

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I have only briefly read the excerpt but I feel that 4 weeks wouldn't be long enough to come to any conclusions as to how hypothyroid patients feel when T3 is added.

My understand is that TSH is only a measurement of how the BRAIN responds to thyroid medication and not how the actual glands respond.

Pam
 

Wishful

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Measuring only Tsh might be useful for detecting common thyroid problems, but shouldn't be used beyond that. There are medical problems aside from the thyroid that affect Tsh, and medical problems that exist even with a 'normal' value of Tsh.

In the pituitary enlargement case debored13 posted, I note that the T4 dose was quite high: 175 mcg. I wouldn't automatically consider that a concern for people who are taking far lower doses.

What I wonder is how many people would benefit from supplemental T2. It has a strong effect on me, while T4 and T3 don't. Maybe the medical community is still stuck with the pre-1960's belief that T2 is inactive.
 

debored13

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These studies. are for people with hypothyroidisn, not people with ME/CFS, chronic Epstein Barr, or who are otherwise chronically ill. Antibodies and reverse T3 weren't measured. TG gene status wasn't taken into account. Nor were selenium or iodine status. Or gluten consumption.

We are not widgets. We are unique individuals with individual genes, infections, nutrient status, etc. I have lost faith in any RCT dictating what I'm going to do because I am 100% sure that the people in these RCTs cannot be anything like me.

Now, what problem are we trying to solve here?;)
i take t3/t4 But was sorta playing devils advocate by posting this here. It’s just a couple studies but I can’t seem to find any studies showing benefit from t4/t3 combos. I am curious as to why that is. Blanchard thinks it’s because the t3 doses normally used are too large
 

Iritu1021

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@debored13
Blanchard also thought that not everyone needed T3.
I think you said you are taking 25 mcg of T4 - that might not be enough for you. You may need 50 mcg or more.

In my experience, other supplements, moods, neurotransmitters, sex hormones, circadian rhythms and cortisol or stress level will cause T3 conversion to fluctuate in susceptible people and make constant level T3 dose not a sustainable treatment option.

I also don't put too much stock in RCT trials but they do show that only 1/3 of patients felt better with the addition of T3, 1/3 felt worse and 1/3 couldn't tell the difference.
 

debored13

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I think you said you are taking 25 mcg of T4 - that might not be enough for you. You may need 50 mcg or more
I was at 25 mcg for awhile and tried going higher. It always seemed to make me a tiny bit hyperthyroid but not cure my cfs symptoms. Aka I would get uncomfortable feeling and overly hot feeling and have heart palpitations but I would not be more energized and I would still be bedridden. I simply don’t think thyroid issues are at the root of my illness anymore. Although I feel worse if I don’t take any I think I’ve hit my peak.

However I found a copy of the Goldstein book on libgen and am looking at some new treatment ideas as well as going to another specialist soon.

I would still be interested in triac if I ever figure out where to get it
 

Wishful

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@debored13 , your experiences are the same as mine. When I discovered that iodine triggered temporary remission, I thought that thyroid problems must be the cause of my symptoms. 25 mcg T4 didn't do anything for my symptoms. Doubling that made my heart race a bit, but no other effect. I also tried desiccated thyroid: no effect. That convinced me that my thyroid gland wasn't the problem. T2 does have an effect, but only with an abrupt rise, not with constant supplementation.
 

debored13

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@debored13 , your experiences are the same as mine. When I discovered that iodine triggered temporary remission, I thought that thyroid problems must be the cause of my symptoms. 25 mcg T4 didn't do anything for my symptoms. Doubling that made my heart race a bit, but no other effect. I also tried desiccated thyroid: no effect. That convinced me that my thyroid gland wasn't the problem. T2 does have an effect, but only with an abrupt rise, not with constant supplementation.
To be clear thyroid does “help” it’s just that it helps a small amount, like if I stop it I do worse but there’s certainly a ceiling effect and it’s not at the root of my symptoms. In an interview I found Paul cheney, one of the original Tahoe docs that treated this illness and did a lot of research , elaborated on the idea that oxidative stress is a major player if not the root cause of the illness, and that the energy metabolism problems were secondary and adaptive. Thus a lot of people don’t tolerate stimulants very well and Cheney cautioned against thyroid use to treat cfs although some have had success with it and I think it’s fine as long as you start small. It’s jnteresting to me that he said this before Naviauxs “dauer “ theory but it’s a similar kind of theory. That interview had lots of good info and one of the things he talked about is really high dose magnesium being helpful against oxidative stress and for the specific energy problems me/cfs patients have
 

Wishful

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I didn't notice even a small difference in symptoms while on thyroid supplementation. I do have slightly elevated Tsh, but I attribute that to elevated kynurenines (specifically picolinic acid).

I haven't found any benefits from antioxidants either. Many of them make my symptoms worse. Peroxynitrite scavengers are even worse. If there was a suitable peroxynitrite booster, I'd give it a try, just to see if it had an effect.
 

Iritu1021

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Thyroid hormone is definitely part of the riddle for many. and it's the first step because it can give people the power and ability to think and intuit themselves better, and to tolerate other meds. But it's still just the first step.
 

Learner1

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In an interview I found Paul cheney, one of the original Tahoe docs that treated this illness and did a lot of research , elaborated on the idea that oxidative stress is a major player if not the root cause of the illness, and that the energy metabolism problems were secondary and adaptive.
Oxidative and nitrosative stress can for peroxynitrites and damage mitochondrial membranes and impair complex I.
Thus a lot of people don’t tolerate stimulants very well and Cheney cautioned against thyroid use to treat cfs although some have had success with it and I think it’s fine as long as you start small.
Most psychiatric drugs deplete nutrients like folate which can, in time, cause new problems.
It’s jnteresting to me that he said this before Naviauxs “dauer “ theory but it’s a similar kind of theory. That interview had lots of good info and one of the things he talked about is really high dose magnesium being helpful against oxidative stress and for the specific energy problems me/cfs patients have
High dose magnesium will not go get rid of oxidative stress by itself. One needs other cofactors, or an antioxidant like glutathione to do so.