To T3 Or Not To T3

[PR4NOW]

Medscape has a rather good write-up on the ATAs recent annual meeting. There are some interesting comments in the article. PR

The conclusion — that evidence is still insufficient to choose 'to T3' — specifically, to routinely combine triiodothyronine (L-T3) with synthetic thyroxine and levothyroxine (L-T4) in the treatment of hypothyroidism — was not, in the minds of some, the nobler of choices, and the ATA subsequently found itself the target of more than a few slings and arrows.

"The use of combination therapy is clearly a very emotive issue," said presenter Jacqueline Jonklaas, MD (Georgetown University Medical Center, Washington, DC), head of the ATA task force on the new hypothyroidism guidelines, underscoring her point with a sampling of postings on the ATA's Facebook page following the recommendation: some calling the decision "shameful," others accusing the ATA of being in the pockets of the pharmaceutical industry, and at least one battle cry for a class-action lawsuit.

Dr Jonklaas noted that even some of the guidelines' own reviewers questioned the decision. She shared a couple of their comments, including: "I do not understand why the authors would not recommend a therapeutic trial of low-dose T3, even though the benefits may be unproven," and "I (personally) think that not mentioning a therapeutic trial with low doses of T3 is unnecessarily rigid, if these guidelines are for practicing physicians."

In a stance seen as somewhat bolder than the ATA, the European Thyroid Association (ETA) has specifically addressed combination therapy in guidance published in 2012 (Eur Thyroid J. 2012;1:55–71) , which opened the door for L-T4 and L-T3 combination therapy "as an experimental treatment modality" for hypothyroidism in compliant L-T4–treated hypothyroid patients who have persistent complaints despite serum thyroid-stimulating-hormone (TSH) values within the reference range.

But among the most important phrases in the new ATA guidelines that should be underscored — loud and clear — is that they "recommend only against the routine use of combination therapy," said ATA president elect Antonio C Bianco, MD, PhD (chief of the division of endocrinology, diabetes, and metabolism, University of Miami Miller School of Medicine, Florida), who cochaired the hypothyroidism task force along with Dr Jonklaas.

"At the same time, there are multiple instances in which combination therapy is supported," he told Medscape Medical News.

Those instances include when patients' serum TSH levels are normal but they are still symptomatic — which is when most clinicians are likely to consider the option.

"I suggest Armour to patients because it's economical and it's simple," said Gary Pepper, MD (Palm Beach Diabetes and Endocrinology Specialists, Jupiter, Florida), a strong proponent of the use of desiccated thyroid. "One problem with combination therapy [with synthetic T4 and T3] is that people find it to be very hard to take three pills a day, and you only have to take one Armour," he told Medscape Medical News. "Furthermore, the synthetic T3 is very expensive, so I'm really looking at it from a more practical point of view."

Dr Pepper, who regularly treats patients with Armour — but underscored that he has no relationship with the makers — responded that the T4:T3 ratio is not as fixed a ratio as the guidelines suggest.

"It's important to remember that the ratio is just an average, and anyone who has done research on this knows that the ratio doesn't apply to everyone," he said. "There are some, particularly patients who don't create T3 as well, who don't fit into those margins, so the argument is extremely weak.

"Furthermore, we are specialists, after all," he added. "You monitor the patient's blood levels and adjust the dose as is appropriate."

The same applies to the risk for thyrotoxicosis, Dr Pepper said.

"Regarding the theory that it could be dangerous — where are the case reports of people getting sick? You will not find a single scientific paper stating any real danger from desiccated thyroid, and as far as I'm concerned, the [medical societies] are scaring people away from this."

"I have patients who are 60 and 70 years old who are taking this medication, and I can tell you they are delighted with it."

This link should be the public access version.

medscape.com/viewarticle/83...

[humanbean]

Unfortunately I couldn't get your link to work. I get asked for a password.

[PR4NOW in reply to humanbean]

humanbean, you used to be able to sign up for free but it has been a few years since I did that so I'm not sure if the rules have changed or not. PR

[humanbean in reply to PR4NOW]

I must admit I've never got around to registering. I'll have a go later.

[PR4NOW in reply to humanbean]

humanbean, I changed the link. PR

[helvella]

Thanks, PR.

Can't help wondering at this comment:

"I have patients who are 60 and 70 years old who are taking this medication, and I can tell you they are delighted with it."

What happens after 70?

Rod

[shaws in reply to helvella]

The 70's+ are so happy and healthy they don't need anything except NDT and have little need for Endos.

[Louwelsa in reply to helvella]

I am 80 and have taken it since 16 years of age and Armour has never given me problems.

Dotty

[PR4NOW in reply to Louwelsa]

Louwelsa, you were lucky to get diagnosed at 16, that must be an interesting story. PR

[Louwelsa in reply to PR4NOW]

The story is that I had no energy, I would sit and look out the window , had no desire to do anything different. Would diet and couldn't lose an ounce, I had great parents and they observed I didn't have any energy, and took me to the Doctor. He gave me a thyroid test, not the one they give now, I think they called it a metabolism test. It showed I had a metabolism of a vegetable. They started me on Armour and upped after time. That is how I was diagnosed

[MLML6 in reply to Louwelsa]

This is interesting. Do you remember what this metabolism test was? I guess it wasn't a blood test.

[PR4NOW in reply to MLML6]

MLML6, it was probably a variation of the BMR (Basil Metabolic Rate) test which was introduced in the 1930s and was the first attempt at a laboratory standard. PR

[MLML6 in reply to PR4NOW]

Thanks. This seems to confirm that the Basal Temperature Test as recommended by Dr. Peatfield and the Broda Barnes Foundation has its place as a useful self-help tool .

[PR4NOW in reply to MLML6]

It is a useful tool. I think the reason it never caught on is because it is non-specific, low pituitary, low adrenal, and starvation can all affect temp. For me it has been much more relevant than any serum test. PR

[MLML6 in reply to PR4NOW]

I entirely agree.

[Louwelsa in reply to PR4NOW]

I do not actually remember the the test it was given in 1950, I was born in 1934. You are probably correct in your assessment

[PR4NOW in reply to Louwelsa]

About the only two tests at that time were the BMR and the PBI serum test which was introduced around 1941-42. PR

[HIFL in reply to Louwelsa]

Hi Louwelsa. Can I ask what your current dose of Armour is, and has it ever changed at all since you were 16?

[Louwelsa in reply to HIFL]

I left the information on Shaw's question, but will repeat. I cannot remember the first dose I was prescribed, but I am currently and for many years taken 120 Mg. of Armour daily. Doctors have tried to put me on synthroid, but t4 does not do anything for me, leaves me a vegetable NDT is the only way for me..

[HIFL in reply to Louwelsa]

And may I ask, do you have any TSH at this dose?

[Louwelsa in reply to HIFL]

My last test on Oct 27, 14 shows TSH at 0.01, it has been the same for the last 3 yrs.

[shaws in reply to Louwelsa]

As the saying goes 'the proof of the pudding'. From 16 years old you have taken Armour and are still going strong. Stronger and healthier than the ones prescribed synthetic levothyroxine half or 1/4 your age. What an advertisement you are for NDT - I wish the British Thyroid Association would take notice.

Thanks for posting and best wishes.

[Louwelsa in reply to shaws]

Yes I am still going strong, and I am and have taken 120 mg of Armour daily for many years. I cannot remember the does I started with, but it was lower at 16. Every one around me is astounded when I tell them my age is 80. I do not look or feel my age. Merry Christmas!!!! If I can be of help in any way, let me know, Would like to help to promote NDT. T4 products do not work for me, and I am sure other people are suffering with these synthetic products.

[shaws in reply to Louwelsa]

I think you will have to be our 'Poster Girl - long life and active, thanks to NDT'. I assume you never had blood tests when you were first diagnosed but due to your clinical symptoms alone.

It will encourage lots of members who are restricted to levothyroxine alone and have constant ill-health and no support from doctors as they will only prescribe generic levothyroxine.

One of the worst phrases I ever heard was from a speaker at the American Thyroid Association's Conference 2013 where he announced that if patients were dissatisfied with levothyroxine but the TSH was in range if they were still complaining they should be diagnosed with a "Somatization Disorder".

(even though their pain was real?).

I assume that this Conference was funded by the manufacturers of levothyroxine and I know doctors also get monetary rewards for prescribing.

It was very heartwarming to read your post.

Best wishes

[RedApple in reply to shaws]

Poster Girl for NDT, what a great idea Shaws!

[PR4NOW in reply to helvella]

Rod, if you want to study the 70+ population Miami would be prime real estate. Other parts of Florida could also qualify, St. Petersburg, FL used to be called 'God's waiting room'. PR

[shaws in reply to PR4NOW]

And is God still waiting?....

[PR4NOW in reply to shaws]

shaws, not as much. As the high proportion of the older population died off in St. Pete a demographic change took place with the younger generation moving in and skewing the ratios back to a more normal distribution. However, Florida still has a high number of elderly in the state and tends to be fairly conservative. I lived there for 26 years which was about 25 years too many, I prefer the plains, the mountains and the west coast. PR

[shaws in reply to PR4NOW]

Yes, your ideal abode sounds lovely.

[shaws]

I am now a big fan of Dr Gary Pepper who talks sense instead of the 'non-sense' of the ATA and BTA.

Let's hope that good can come out of the Medscape and patients are made well, instead of kept unwell by the 'powerful' (small letters).

Thanks PR for some hopeful and uplifting news.

[Clutter]

It's an interesting softening of attitudes, PR, but still reinforcing prejudices about T3 and NDT. The ETA guidelines are also very anti NDT.

[PR4NOW in reply to Clutter]

Clutter, change is a very slow process, unfortunately, but this does reflect the growing discontent of millions of us with the inferior standard of treatment that we are subjected too. Our voices are being heard, they just don't know how to react. I actually think 'somatoform disorder' and the 'ethics guidelines' are the most dangerous aspects of the new guidelines. It just may take a class action lawsuit before real change occurs. PR

[humanbean]

I finally registered with Medscape and read the article. It seems obvious to me that many doctors simply don't get it, when I read stuff like this (I added the bold effect) :

"We don't have a good sense of how many people are over- or undertreated in these combination-therapy regimens," Dr Jonklaas said. "We also do know there were some reports of side effects and concern about cardiac arrhythmia, with one report of atrial fibrillation."

"All of these are reasons arguing against 'just giving people L-T3.' "

Dr Bianco concurs: "Given that this is a lifelong therapy, ideally we would like to know that this is safe [and] that it [will not harm] patients in 10, 20, or 30 years before we make the recommendation that all patients can routinely use combination therapy. In contrast, safety data do exist for L-T4 tablets."

So, they worry about how healthy we will be in 10 or 20 or 30 years time, but don't seem to care in the slightest how well we feel NOW! And, as PR4NOW mentions, the worrying thing is somatoform disorder. Not only is our quality of life ignored and considered to be irrelevant, but now we are accused of being mentally ill too.

[stiltzski in reply to humanbean]

Well said! I went to the osteopath yesterday to try and ease some of my pain and he pretty well said my symptoms were caused by stress although he did add that he was not saying it was all in my mind! He even said that the pain was not 'real' pain!! My answer was that he would be stressed if he was in as much pain as I was! Goodness knows what I am going to feel like in a decade...I am 61...but at this rate I don't think I will even get there. It is just so depressing that the medical profession won't wake up to The Thyroid Madness. My nephew is a young doctor and I once thought I might be able to convince him but no way...

[Hidden]

If I read this correctly among the reasons given against combined therapy; T3 is difficult to take 3x per day and more expensive... !!!

I find this pathetic evidence against combined therapy. Sums up the 'experts' completely. Patronising & budget driven. When it comes to my well-being would I accept this as medical evidence that T4 alone is better for me? Absolutely not. Thank God I'm not dependent on experts.

[CatSlave]

All,

Great to see some progress. One cannot help feeling big pharma's long arm exerting pressure here:

A primary reason given for not more strongly supporting the likes of armour, are complaints that so few clinical trials exist which study its efficacy. Armour was developed before patent laws case into play, which means it was "grandfathered" into the system. It also means big pharma does not stand to gain huge sums of money: what they cannot patent, they cannot guarantee years of dosh flowing in as they overcharge.

Why not call on british medical authorities to launch such a study? Surely it would be in their interest: without a patent the NHS might stand to save money. (Do i hear you shout, "NICE"?)

I went on to read thru the european guidelines published 2012. Striking conclusions, in summary: studies in rats show that t4 treatment alone utterly fails to restore correct t4/t3 at the cellular level in all the body's different tissues. ONLY combination therapy of t4/t3 did. The study goes on to be hyper cautious about conclusions to be drawn in terms of humans, saying only that there might be something which explains why a significant percentage of us continue to be unwell on t4 only. Here's the significant quote from those recommendations, about the rat study (so sorry for the poor rats!!!!):

Administration of L-T4 alone to thyroidectomised rats does not, at any dose tested, result in normal T4 and T3 concentrations simultaneously in all tissues (which can be taken as one criterion for defining euthyroidism) [32]. The L-T4 dose needed to normalize thyroid hormone concentrations was different for each tissue, and supraphysiological T4 concentrations had to be reached in most tissues to normalize their T3 concentrations. Only the combined treatment with L-T4 and L-T3 resulted in normal T4 and T3 concentrations in plasma and all tissues as well as normal serum TSH and near-normal D1 and D2 activities [33]. The addition of small doses of L-T3 decreased the amount of L-T4 needed to normalize T3 in the majority of tissues by about 50% compared to the amount necessary when L-T4 alone is used. Combination therapy ensuring euthyroidism in all tissues at the same time was only obtained at a dose of 0.90 μg T4 and 0.15 μg T3 per 100 g body weight per day; the molar ratio of the T4 and T3 dose is 5:1, similar to that present in the normal thyroidal secretion of the rat.

When extrapolating these observations in rats to humans, one should realize that the relative importance of thyroidal T3 secretion versus extrathyroidal T3 generation from T4 is greater in rats than in humans. The molar ratio of T4 to T3 in thyroidal secretion is ~5.7:1 in rats and ~14:1 in humans [1]. Nevertheless, the rat findings suggest the possibility that the treatment modality with L-T4 alone might be inadequate.

Printing and highkighting for upcoming endo visit