Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study.

[helvella]

Those who have been here for a while might remember that there has been a trial comparing desiccated thyroid extract against levothyroxine.

Trial:

clinicaltrials.gov/ct2/show...

Earlier Blog:

thyroiduk.healthunlocked.co...

(I thought there had been an earlier blog but either my memory is broken or the HU search is not being very helpful.)

The trial appears to have been completed and, now published! Unfortunately, for now only the abstract appears to be available.

J Clin Endocrinol Metab. 2013 Mar 28. [Epub ahead of print]

Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study.

Hoang TD, Olsen CH, Mai VQ, Clyde PW, Shakir MK.

Source

Department of Endocrinology (T.D.H., V.Q.M., P.W.C., M.K.M.S.), Walter Reed National Military Medical Center, Bethesda, Maryland 20889; and Department of Preventive Medicine and Biometrics (C.H.O.), Uniformed Services University of Health Sciences, Bethesda, Maryland 20814.

Abstract

Context: Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (l-T4), occasionally did not feel as well despite adequate dosing based on serum TSH levels.

Objective: Our objective was to investigate the effectiveness of DTE compared with l-T4 in hypothyroid patients.

Design and Setting: We conducted a randomized, double-blind, crossover study at a tertiary care center.

Patients: Patients (n = 70, age 18-65 years) diagnosed with primary hypothyroidism on a stable dose of l-T4 for 6 months were included in the study.

Intervention: Patients were randomized to either DTE or l-T4 for 16 weeks and then crossed over for the same duration.

Outcome Measures: Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated.

Results: There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred l-T4, and 23 (32.9%) had no preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both). Five variables were predictors of preference for DTE.

Conclusion: DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over l-T4. DTE therapy may be relevant for some hypothyroid patients.

PMID:

23539727

[PubMed - as supplied by publisher]

ncbi.nlm.nih.gov/pubmed/235...

As posted on the journal's web site:

jcem.endojournals.org/conte...

I feel that making any comment right now is inappropriate - I want you to read and comment without influence from my blog. Also, lack of further detail makes proper assessment very difficult - actually, impossible!

Rod

Picture is of Walter Reed - a physician - after whom the medical centre at which this trial was run was named.

[12:59 31/03/2013 Edited to include this link:

The supplementary data for this paper is accessible here:

jcem.endojournals.org/conte...

That includes things like the TSH ranges before, on desiccated and on levothyroxine.]

11/10/2013 UPDATED - Full Paper Available

The paper can now be obtained by following the instructions here:

endojournals.org/site/misc/...

The paper can be identified by quoting:

Thanh D. Hoang,

Cara H. Olsen,

Vinh Q. Mai,

Patrick W. Clyde,

and Mohamed K. M. Shakir

Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study JCEM jc.2012-4107

[Hidden]

Sorry Rod, was just chasing after the tumbleweed that blew across my latest blog, it rolled through here and looked like it was headed towards your magnesium blog....!

shhhh - you could hear a pin drop in here today!!

xxx

[helvella Administrator in reply to Hidden]

Certainly could!

Shame as the paper reported here could prove to be very important!

[galathea]

Well Spotted!

so, there is no difference between NT and levothyroxine and the NT did not improve quality of life.... but nearly half the group expresses a preference for it!

Hmmmm do you think perhaps that they are measuring the wrong thing? I prefer NT because of the even steady feel it gives compared with T4 or t3/T3. I wonder what they call the even steady feel and if and how they measured it

G x

[Hidden in reply to galathea]

Hey G!

Not seen you around for a while - hope all is well! xxx

[helvella Administrator in reply to galathea]

I guess it is down to how they measured quality of life.

Maybe we should be thankful that it has not come out with any obvious negatives!

[galathea]

Hi, everything fine!

G

[vajra]

It's hard not to conclude from research like this (that is statistically based research structured around the presumption that one size fits all) that medicine and the various related industries have little or no interest in treating patients on an individual basis.

That is in the case of thyroid in being guided by symptoms to establish a replacement routine optimised to individual needs.

Yet it's patently obvious to anybody that looks in on forums like this that there is a lot of variation in the replacement regime that works best for a given patient. i.e. NDT (which if nothing else implies a specific mix of the different thyroid hormones) won't necessarily be optimum for everybody.

That's before as you say the likelihood that dosing to a pre-determined standard TSH blood value is (of itself) enough to deliver a poor result is considered.

As ever big money and its search for blockbuster one size fits all therapies gets to set the agenda. By indirect means if nothing else - research it seems is no longer respectable these days unless it's based on statistical methodologies, and targets whole populations.

It's hard not to conclude that medicine has little interest in treating patients by other more labour intensive and less profitable means.

Never mind that symptom based treatment need not necessarily be so labour or cost intensive. It would however require properly co-operative doctor patient relationships becoming the norm - and that would require our taking a lot more responsibility for ourselves.

Conclusion: 'DTE therapy did not result in a significant improvement in quality of life'.

How could it have done so in that test? Who anyway is arguing that it necessarily will do so for everybody?

The conclusion is far too generalised. By the structure of the trial the result incorrectly implies that the outcome is applicable to all patients in all modes of treatment using DTE - and that's before as you guys say the glaring issue of how most can have preferred it yet the test reports no significant improvement in quality of life is considered....

ian

[vajra]

PS The word 'significant' (see conclusion) has a very specific meaning in statistical research - bet there were more than a few in the study group that did much better on DTE.

Bet too that 'occasionally did not feel as well' (see context) means that rather more than a few reported problems on synthetic hormone - it seems highly unlikely that the research would otherwise have been carried out.....

ian

[Hidden]

Looks like a classically "loaded" trial to me... and will be quoted for evermore as "Evidence based medicine" for decades to come - take a bunch of people who already do well on T4 only, and swap them backwards and forwards for just short periods on that and NDT, and you find there isn't much statistically to chose between them.... especially when you only look at certain parameters. Now take a bunch of UNSTABLE patients who aren't doing too well on T4 only and try that and it might or might not be interesting to see the difference.

[Glynisrose]

Surprise surprise!! They did a study and discovered...... what they had said all along!! Seems to me another case of only finding what they were looking for otherwise pre-determining the answer before the question was phrased!!

[poing]

I thought this study was going to run until May 2014. Has it been cut short?

16 weeks seems barely long enough to determine the correct dosages when changing from one treatment to the other. I wonder how the equivalent dosages were worked out?

If the study methodology is flawed, then people doing meta-analyses will be at liberty to ignore it in future.

Not that it says much anyway. Grrr.

[superb_lulu]

Hey all.

I dont understand why Erfa, who manufacture NDT, would share research that does not endorse their product? Seems odd... unless I have missed the point.

Lulu

[helvella Administrator in reply to superb_lulu]

It doesn't slate their product which is a huge step away from the "the only medicine is levothyroxine" statements which have been so common. The fact that the actual maker of the product in the research is another company does not invalidate the "quite a few people felt better on desiccated thyroid" (or words to that effect) statement which would be likely also to apply to their own product.

They also know that anyone looking would be able to find this information so they can gain some brownie points for sharing it.

Rod

[tavy]

to me that says that it can make a difference to some, the ones who have a problem with t4. surley we are worth a trial ???

[helvella Administrator in reply to tavy]

Seems reasonable, doesn't it?

Rod

[TheKite]

Hi all,

I am a patient advocate here in Australia (long story short - thyroid out, nearly died on T4 (despite 'normal' blood tests) recovered on Desiccated Thyroid), and have recently been given a copy of this trial.

The abstract, I have to say is very misleading. I understand that going up against big pharma is scary, but still.

Let me copy and paste a few choice pieces from the trial...

Subgroup analyses

Patients preferring DTE had an average of 4 lb weight

loss during the DTE treatment compared with the L-T4

treatment (P.001), and their subjective symptoms, such

as concentration, memory, sleep, decision-making capability,

happiness, and energy level, were significantly better

while taking DTE as indicated by lower GHQ-12 and

TSQ scores (P.001 for both comparisons) (Supplemental

Table 1). The BDI was nearly (P
.057) improved.

Auditory memory also improved in these patients during

the DTE treatment period (P
.041).

(sounds like a massive success to me)

Adverse effects

No adverse effects were reported with any of the treatments.

All patients tolerated both treatments equally well.

(finally!!! Proof that desiccated will not cause adverse effects which is the standard scare tactic)

Overall, the patients lost approximately 3 lb during the

DTE treatment compared with L-T4 treatment (P 

.0001). Despite the increase in serum T3 level, the DTE

treatment did not cause any symptoms pertaining to the

cardiovascular system or changes in heart rate and BP.

It should be noted that previous studies on L-T4 versus

L-T4 plus L-T3 had problems with reduced TSH in the

L-T4 plus T3 arm, suggesting slight overtreatment, which

could affect the outcome. However, our study showed

significantly higher TSH in the DTE-treated group, which

suggests that the improvement observed in the DTEtreated

group is not mediated through the changes in TSH

levels.

Clinical preference

At the end of the study, 34 patients (49%) preferred

DTE, 13 (19%) preferred L-T4, and 23 (33%) had no preference.

Preference for DTE over L-T4 was statistically significant

(2 [1]
9.38; P
.002).

I hope this sets your mind at ease a bit.

From the abstract alone, it feels like the trial was a bit of a let down, especially for those of us who are only well because of DTE. But, considering the TSH was actually a bit higher in this for DTE as compared to T4, if they had matched the TSH, or even trialed DTE at levels that made use feel better despite TSH the results would have been even more positive.

Keep up the good fight

[helvella Administrator]

The paper can now be obtained by following the instructions here:

endojournals.org/site/misc/...

The paper can be identified by quoting:

Thanh D. Hoang,

Cara H. Olsen,

Vinh Q. Mai,

Patrick W. Clyde,

and Mohamed K. M. Shakir

Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study JCEM jc.2012-4107;

Rod

[Nat107]

Everyone is different and should be treated as so, we should be given the opportunity of trying alternatives to Levo if we feel we arent responding very well to levo. We no our own bodies best And a 6 month trial is no way

near enough time for either treatment to make a complete diagnosis of either treatment on each person. Took 18 months for Levo to even slightly make a change to me and still don't feel right after 20 years on it.

Lets hope we can get NDT back on prescription in the UK without having to highlight to doctors Levo just don't work for everyone

[helvella Administrator in reply to Nat107]

Certainly agree that people should get the best treatments for them.

I get the impression that the people running the trial would agree that six months is not enough. Considering the lack of any proper trials, even this limited one is a step in a positive direction.

Rod

[Nat107 in reply to helvella]

Yes it is, i Certainly agree, hopefully the first of many to come, hopefully