Below is an extract from this website. What I found interesting was that a study done with 2 grooups one on T4 and the other T4/T3. Then they did a swap and preformed a cross study and proved that there was a difference to paitents whole well being. Teh orignal T4 who then swapped to T4/T3 felt well. The T4/T3 who then took T4 felt worse and developed the classic symptons. Also goes into how relying on the clincial TSH results is not the wonder work Drs seem to think.
More also that the life of these tablets we take and the prime time when our TSH should be taken as its lowest point is mid afternoon.
Did you know we are supposed to have regular testing for serum cholesterol and
A trial conducted by Bunevicius and colleagues in the Untied Kingdom about the thyroid issues of T4 vs T4/T3 combination and effects on general whole body health.
T4/T3 Combination Compared with T4 Monotherapy
The recent resurgence into hypothyroidism treatment research derives from the experience of clinicians who found that some patients remain symptomatic while on prescribed T4 replacement therapy. For example, 1 survey conducted in the United Kingdom revealed that patients treated with T4 had significantly more psychological morbidity compared with euthyroid controls.[37] This was supported by findings in animal models, where hypothyroid rats realized normal thyroid hormone levels on a combination of T3 and T4 (in the ratio normally secreted by the rat thyroid gland) but not with T4 monotherapy.[38] This led to a landmark study by Bunevicius and colleagues who assessed whether T4/T3 combination therapy had any advantages over T4 monotherapy for hypothyroidism (Table 1).[19] To compare therapies, they used a crossover study design with 33 patients on different regimens of monotherapy and combination therapy over 2 different 5-week periods.[19] Combination therapy was achieved by replacing 50 µg of the patient's usual T4 dose (ranging from 100–300 µg/day) with 12.5 µg of T3.[19] Patients who received combination therapy had lower total and free T4 levels and higher T3 levels than patients who received T4 monotherapy. It was reported that cognitive performance and mood were significantly improved or normalized after treatment.[19] These findings prompted a series of papers aimed at assessing the potential advantages of combination therapy over monotherapy for hypothyroidism.[19,39–43]
Following the landmark paper, Bunevicius and colleagues performed a second crossover trial in women who had undergone a subtotal thyroidectomy as a treatment for Graves' disease (Table 1).[44] In this study, T4 therapy consisted of either the patient's regular dose of T4 or combination therapy, which was achieved by replacing 50 µg of the usual T4 dose with 10 µg of T3. After a period of 5 weeks, the patients were crossed over blindly to the opposite treatment. In patients who received combination therapy, the severity of symptoms of hypothyroidism and hyperthyroidism had a tendency to decrease, as indicated by patient scores on a standard symptom scale. Mental status also tended to improve with combination therapy compared with monotherapy, based on apparent improvement in mood (indicated by Visual Analogue Scale [VAS] scores). However, there was no difference in cognitive performance improvement (indicated by improved scores on the Digit Symbol and Digit Span tests of the Wechsler Adult Intelligence Scale). Although this study was small (n=13), the authors concluded its findings were consistent with those of their earlier study in terms of demonstrating a relationship between T4/T3 combination therapy and improved mental function
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They received a Rebuttal from Dr John Lowe re the above as well as their stance on Armour Thyroid and Dr L said how can they not be prosecuted by the authorities for making false statements but the BTA ignored this Rebuttal with the result that the suffering continues.
shaws, it actually is kind of an interesting article. They review several of the comparative trials that have been done regarding T4 only versus T4/T3 and then go on to point out that we really don't understand a lot about what happens in the brain and that there just might be some benefit to T3. Granted they call NDT 'crude' but it is nice ocassionally to see researchers admit that there is a lot they simply do not understand yet. It is a bit of a long read but it is a good example of how difficult it is for science to understand what many of us have had to learn by trial and error. PR
I get frustrated when so many studies have been done re T3/T4, which get ignored and patients are left suffering . I myself had a great benefit by the addition of T3
This is another done by Dr Toft ex President of the British Thyroid Association I believe published in 2003.
So many doctors are mean with their prescribing and keep patients within the reference range, who have no quality of life and with so many awful symptoms.
Plus the first treatment of a woman in the UK in 1891
Interesting stance by the British Medical Board. On one hand it knows and seemingly acknoweldges that the combined T3/T4 has benefitted people. Wheras the T4 only has not. They also admit the It remains sceptical as to why.
My view point they are being cautious, probably a bit too much. I would not be shocked to find out that those on t4 only with symptoms probably add up to more than those on t4/t3.
But then again why let those with , say with 50% symptons continue to suffer and damage their health?
As I know Addisons Disease and the Addisonion Crisis, via my dog. having set about to find what was wrong with my Vet. Since diagnosed and brought back from iminent death. I did a lot of research. Peace of mind as I was terrified when this hit her out of the blue. Hand on heart I would never want that disease. In humans with Addisons, the ignorance they encounter is truelly shocking. Probably far worse than us Thyroids. I do not trivalise us thyroids either. We are very much in the same ball park along side the Addisons, Cushings, Diabetes, Meningistis sufferers. All with unique markers but many shared symptons and issues.
So on that basis I do understand the intricate natures of the whole endo system. In and Addisonion crisis, , the basics affect, it is a bit more long winded. During the crisis the calcium is forced out of the bones, turning them soft so you are unable to support your own body.. Potassium is then sent sky high and sodium plummits. The adrenal glands are the fine tuners there. It is fine tuned to deal with any changes, probably within minutes of need requirement. For Addisons, the suffer must take florineff, the adrenal hormone and steriod for life.
Now the interesting part. Stress being one of the biggest factors that influence the endo system. Stress people assuem the pressure of work, got to do this, get this done, rush rush etc. Wrong. Stress is both the bad, rush must pressure, but also the happy stress.
I will own up to thinking stress = bad not there were other forms.
Easily explained using my poor old dog. I rescued her from an abusive drukn druggie owner. So poor dog came with baggage huge trunks of. One in particualr is, she is terrified of tiled floors due to her being abandoned in a kennel whilst its owner claimed to be away on holiday. Now the Vet has tiled floors, so its a reactor for her.
Soon as we go int the vets she starts vibrating as I call it. She shakes very noticably. Now that is a bad stress.
Take her for a walk which she loves, and she again shakes - this is a good stress.
Without her flourinef and steriod, either scenario would send her directly into and Addisonion crisis, within minutes she would collaspe,unable to support herself. Shaking would become violent, hair would fall out, breathing would become laboured and her internals would begin to shut down and toxify as she began to die.
To reverse this, she would be pumped full of insulin then given a steriod. Within minutes of the steriod being transfused she would be stadning and acting like nothing.
So stress affects us and the Endo system compensates by producing what we need there and then, be it adrenalin to fight or flight, coritsol, thyroxine etc.
Weight- the other silent factor. Like with my dog her flourineff is based on weight to meds ratio. If she gains, up the amount needed, weight down less is needed.
Thyroid is also weight dependant. Yet they ignore this factor when working out dosages. My Dad had Graves, and his thyroid is dead. The Drs gave him 25mgs of thyroxine. Yet he sufferers on the lower dosage with the same issues underactive have. Yet his Drs refuses to rasie it and quote, "25mg is all the body needs of thyroxine. It needs no more than that." When he said but I am used to high levels and felt fine. The same came back now your thyroid is not working so all you need is 25 mgs thats it. The most anybody needs with an underactive thyroid is 100mgs. Its the guildelines we follow and this is what the dosage is stated to use. My dad is still waiting for a copy of these guidelines he requested to see from his GP.
Which brings us back to the debate on symptons. Many have said, but I feel great on this dose. Then they say but I feel so sick, tired brain dead on this lowered dosage. Endos and Drs ignore and stick to the its in the range. A range that is not applicable to everybody, it is a guideline.
Problem being, one person may find they are happy on 200mgs and another 25mgs. We are all not the same. My weight and sytmprons maybe more than the next person.So our dosages should be different. But why should the Endos and BMB dictate one size fits all. When they know and have seen that this is not always the case. Same applies to the T4 vs T3/T4 case. If some of us feel normal on a combined why shouldnt it be given.After all the more well we feel the less resources and costs we use.
The view held is wrong and as why are they holding such a view and are not being prosecuted by sufferers? The answer to that is a can of worms.
It leads us to the question...Who is ultimately responsible for our well being, is? British Medical Board, British Thyroid society, Endo's, Drs or us?
One would assume that our general whole well being was our responsibility. After all we live day to day as we are.
If that is true so why are the BMB,BTA, Endos, Dr and GPs making such descions on what we are treated with and by which amount, even when that treatment makes us worse or fixes very little. Which leads onto more ailements arising.
The problem is not the principle of medicine. That is to cure or to give a quality of life. It is the method it is delivered that is the brickwall we run into.
Drs, go to school to learn their profession, They then talior that to the field they want to, the sexiest being Heart. They are taught, how, what and to from books, lectures, cadavers. They are not taught to listen and evaluate the whole and talior to the whole. Its the minimum and guidelines only.
It is the whole that needs treating not just one sympton. There lays the cans of worms.
Appelhof BC, et. al. "Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial." J Clin Endocrinol Metab. 2005 May;90(5):2666-74.
It's common knowledge among patients, and some medical professionals, that a substantial number of patients with hypothyroidism will continue to have various complaints and symptoms, despite treatment with levothyroxine that maintains so-called "normal" TSH levels. One study in 2002 found that, (Saravanan et. al. Psychological well-being in patients on ‘adequate’ doses of l-thyroxine: Clin Endocrinol (Oxf) 57:577–585), compared with controls, more than 13% was not satisfied with their health condition, reflecting dissatisfaction with their treatment. The primary complaints were fatigue, weight gain, body aches/pains, and clumsiness.
According to the Bente C. Appelhof, MD, from the University of Amsterdam in the Netherlands, and colleagues: "Controversy remains about the value of combined treatment with LT4 and LT3, compared with LT4 alone, in primary hypothyroidism. It is a well-known clinical notion that a fair proportion of patients with hypothyroidism remains with health complaints, despite substitution therapy with levothyroxine and normalization of serum TSH [thyroid-stimulating hormone] values."
Other animal studies have shown that replacement therapy with levothyroxine (LT4) alone does not ensure euthyroidism -- normal thyroid levels -- in all tissues. Instead, euthyroidism could only be achieved by a combinated treatment of LT4 and liothyronine (LT3). Various studies have focused on this issue, looking at whether LT4 therapy might not be enough to restore euthyroidism in human tissues as well. While patients consistently report a preference for the combined studies, researchers have not been able to isolate specific improvement factor that are clinically measurable.
Now, researchers have identified at least one factor that appears to be related to combination therapy -- weight loss.
Research published in the May 2005 issue of the Journal of Clinical Endocrinology and Metabolism reported on a recent study that found that patients preferred thyroid treatment that included a combination of levothyroxine (T4) and T3, rather than the usual levothyroxine (T4 only) treatment, and that combination treatment was associated with weight loss. This clinical trial is the largest to date, and the first since the Bunevicius study published in the New England Journal of Medicine in 1999 that confirms a beneficial effect of combination T4/T3 therapy for hypothyroidism.
The double-blind, randomized, controlled clinical trial looked at 141 patients with primary autoimmune hypothyroidism, who were broken into groups who were treated with T4/T3 in a ratio of 5:1, 10:1, as well as a group that continued with their previous T4-only treatment. After 15 weeks, the study showed a clear preference on the part of the patients for the combination treatments, and in particular, the 5:1 treatment featuring a higher level of T3, versus the T4-only treatment.
Some particular findings of interest:
A decrease in body weight -- but not a decrease in serum TSH -- was correlated with increased satisfaction with study medication.
In both combination groups, there was a decrease in weight, most pronounced in the 5:1 ratio group, who had a mean decrease of 1.7 kg, or 3.75 pounds. Theh 10:1 group had a mean weight loss of 1 pound. The T4-only group had no change in weight.
Of the patients who preferred combined therapy, 44% had serum TSH less than 0.11.
Measurable changes in mood, fatigue, well-being, and neurocognitive functions could not be identified to explain the patient preference for the combination treatment.
One key flaw in the study was that some patients receiving combination treatment were receiving suppressive doses, which is considered overtreatment. They had TSH levels below the normal range, and would therefore be considered hyperthyroid.
"Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy," the authors write. "Decrease in body weight was associated with satisfaction with study medication."
While the study authors could not find any measurable reason to recommend the combination therapy, they did conclude: "Nevertheless, the outcome of this study does not preclude the possibility that a certain subgroup of patients may benefit from combined LT4/LT3 therapy."
Yes I did. It makes for interesting reading and I have got it earmarked for further reading. Pletchers is a variant, and I'm looking into whether both Addisons and Pletchers can run alongside each other. As like the thyroid being Underactive and Hashis, Hashis and Graves, etc.
Reason being. I am aware of the allergies that can develop and the body struggles to react and isolate the allergens to remove them. Problem here is, my dog has a pedigree heredity of weakness caused by the over inbreeding program the pedigree breeders run. Not all. At the age of 5 years is it common for my breed of dog to develop allergies. these normally are grass, pollen - typical hayfever or mite allergy, flea bit allergies. So when these genetic markers activate in the dogs, those with Addisons cannot cope. My own dog doing just that. She reacted and began swelling, the sweelings were red and hot. until it was so bad she could not see and was double her size. Very frightening and the Vet gave her a super steriod booster and upped her steriods so she could cope. 24 hrs later she was back to normal. So Pletchers on the allergic reaction side on that rings true, but also its the genetic weakness comes into play. Its hard to say if Pletchers is relevant or not.
However in my dogs case she went into direct Addisonion crisis. That was the catalyst and her adrenal glands failed. Treatment for the Addisonion Crisis is specfic. The ATCH test showed the Addisons markers clearly.
The same can be brought into the thyroid, it is linked with Meningitis, Addisons, Cushings, Diabetes, Menopause. Majority of symptons are all same, its just a few that vary but the tests for diagnosis are specfic to each as is the markers identifing which is to blame.
It is clear the Endo system appears to me, not to be that well investigated or perhaps understood is a better choice of words.
ravenhex, my fault, I didn't make my question clear. Dr. Plechner is a Doctor of Veterinary Medicine who has done a lot of research on adrenal problems in animals, especially dogs. He became a vet in 1968 and is one of the few to really study adrenal problems in animals. There are a lot of parallels between humans and animals and the problems both suffer health wise. This is his website.
Just checked my bookmarks and that one isnt in it, but will go have a read tomorrow (hopefully) and get back to you on it.
What youve written about Dr Pletchner finding parallels between the animal and human kingdom, I agree with. Treatment often differs as does some medicines side effects. Chemo for one, dogs dont get the same reaction to it like humans.
Actually, if you read this through to the end, the conclusion is not that great:
Summary
Over the last 4 decades, treatment for hypothyroidism has evolved from the use of crude whole thyroid preparations (which provided both T4 and T3) to T4 monotherapy. This evolution is the result of technological advances, fear of iatrogenic hyperthyroidism due to excessive amounts of active T3, and pharmacological considerations (eg, half life), which enable convenient daily dosing for T4. During this evolution there remained evidence that patients treated adequately with T4 still experienced a number of symptoms, including deficits in cognition and mood, their ability to focus, and their general mental well-being.
An early landmark study by Bunevicius and colleagues demonstrated that T4/T3 combination therapy for hypothyroidism improved mood and cognition compared with T4 monotherapy in patients with chronic autoimmune thyroiditis and post-thyroid cancer total thyroidectomy.[19,44] However, the use of combination therapy remains controversial as several investigators were unable to reproduce these findings in 6 subsequent studies,[40–47] while 2 recent studies support a benefit for T4/T3 combination therapy in specific subsets of patients (Table 1).[46,47] In the recent large studies of thyroid function, investigators identified a substantial placebo effect,[47] which has made it difficult to delineate how combination therapy is associated with clinical benefits. It is also possible that combination therapy only works in a subset of patients because of yet unidentified mechanisms related to the complex and poorly understood T3 and T4 signaling in neurons. Such mechanisms may include differential signaling in response to T3 and T4 in neurons, including T4 signaling through aVßIII integrins induced by MAPK[70] and T3 signaling through PI3K.[68] Regardless of the mechanisms, T3 is increasingly being used as adjunct therapy in an increasing number of psychiatric diseases because of its positive effects on serotonin and the catecholamines.[78–84] Finally, it is possible that combination therapy has no benefits, as was suggested in recent meta-analyses.[86] However, because of our incomplete knowledge of thyroid signaling biology and the complexities of assessing the efficacy of thyroid hormone replacement (Figure 2), it remains to be definitively proven whether combination therapy should replace standard treatment for hypothyroidism.[\b]
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I think you will agree especially the last paragraph is not particularly encouraging for those who have a complex problem.
I've tried to make the last section bold, let's see how it turns out.
I think the problem in these trials is they aren't relaible or can be truely blind tested. Yes they have shown that the T4 can work on some people. Others need the T3/T4 combi. Yes the T4 seem to have more ailments than the T3/T4.
The worse partis the placebo effect. Did the t4 group feel better as the believed t3/t4 was the better treatment? The medical society hate the placebo effect, it cant be explained fully, it cant be produced reliably.
Although the trials in therory support the t3/t4 as patients felt better, without a solid trial that can break down the misconception of the current belief t4 one size fits all, There are always going to be people who suffer when they shouldnt.
And this is the wonderful 21st century, or what century we are in. probably 13th century the way some Drs act, and some of us suffer until somebody steps up and says I say old chaps these thyroidees cost a pretty packet on theis T4, lets switch them to t3/t4 as its cheaper and they may not complain so much the ungrateful wotsits. LOL
Surely if the trials are truly randomised, double blind, cross over controlled trials the placebo effect would be elliminated.
It is the meta analysis trials (where previous trial results are "gone over" ) that worry me, as they can, and I am sure do, choose the trials to suit the outcome they want to prove.
Cynical, who me? Nah
As someone once said there are lies, damned lies and statistics.
Very interesting stuff but shouldn't we avoid having blood tests in the afternoon then? We want TSH to be at its highest not lowest. I think Rod has posted on that point previously.
Siskin, unfortunetly no. The placebo has yet to be fully explained or even produced reliably.
All it is, is it occurs but not why or what.
The true mark held by the scientific community is, you experiement, you run trials, double blind one to get the predicted results. As some of these t3/t4 vs t4 trials show, yes in therory the t3/t4 produces better results in patients. It doesnt give the same predicted scores each time.
Example
Group a, b, c = 3- people, 15 men/15 women or similar ages and sizes with autoimmune under active thyroid all with mid range normal tsh, all on Levothyroxine 100 mgs per day..
First testing
Group a is given t4.
Group b is given t4 plus a sugar pill (placebo)
Group c is given T3/T4
Group A = report 20 same problems - 1- totally better and 4 some improvements.
Group B= report 27 totally better, 2 no change, 1 worse.
Group C = report 30 all better.
Second testing
Group a = T3/T4
Group b = T4
Group c = T4 plus sugar pill
Group a = report 22 totally better, 3 got worse 5 no change.
Group B = report 5 felt better,19 worse, 6 no change
Group c= report 23 got better, 2 no change, 5 worse.
Third testing
Group a =T4 plus sugar pill
Group b = t3/t4
Group c = T4
Group a = report 29 got better, 1 no change
Group b= report 24 got better, 6 no change
Group c= report 30 got worse.
There lies the problem, placebo effect not consistantly recorded. Variable recordings. hence why there are some who stick to the t4 one size cures all. The other side who say t3/t4 helps certain sub groups.
Only thing that the t4 vs t3/t4 that has been noted is weight loss on the t3/t4 combination. That may have lead onto the person feeling better in themselves and the symptons lessened likewise.
A trial of t3/t4 for those underactives who have a weight issue would be a more solid trial to embark on. If those taking the t3/t4 all lost weight and symptons lessened. Then that is one step forward. But the placebo effect could still come into play.
Group a - t3/t4
Group b - t4/sugar pill plus diet
Group c = t4/sugar pill plus gentle exercise.
The problem though is, finding a consistant percentage of those who lost weight by t3/t4 only and did not lose the same weight in the t4 plus gentle exercise and the dieters.
the sceince is flawed anytime the percentages dont tally up.
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