[Harpy July 10, 2012 at 8:32 pm Post count: 184]

#1059194

Stumbled across this study from Japan, published 2010, basically found that remission rates increased in line with the duration of minimal maintenance (MM) ATD dose therapy once FT3, FT4 & TSH levels were normalised. Individuals who stopped all meds after 6 months or less of having normalised levels relapsed more often than individuals whom had an extended period of greater than 6 months MM ATD therapy.
The Link and Abstract below, I don’t have access to the full paper:
http://www.ncbi.nlm.nih.gov/pubmed/21206137

Abstract

According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves’ disease, discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves’ disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb) levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however, this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.

It also re affirms the importance of testing for Antibodies before ATD treatment is stopped.

[KimberlyOnline Facilitator July 11, 2012 at 9:44 am Post count: 4294]

#1172856

Hi Harpy – This is an interesting study, and one I will share with my own doctor when the time comes to talk about discontinuing ATD therapy.

However, it will be interesting to see if these results can be replicated.

There was a study out of Japan about 20 years ago that utilized full Block & Replace therapy to achieve remission in 98% of the patient sample! This created a lot of excitement, but the results were not able to be replicated in other studies. This approach is very rarely used in the U.S., due to the poor track record and the concern that higher levels of meds could increase the risk of side effects.

(Note on links: if you click directly on the following links, you will need to use your browser’s “back” button to return to the boards after viewing, or you will have to log back in to the forum. As an alternative, you can right-click the link and open it in a new tab or new window).

http://www.nejm.org/doi/full/10.1056/NEJM199104043241403

I remember hearing in one of our conferences that patients of Asian descent tend to have improved chances of remission vs. the rest of the population. However, I don’t know if the presenter was referring to people from a specific geographic location…or *anyone* of Asian descent, regardless of where they are living. It would be interesting to see some further study on this to see if researchers can determine if genetics, diet, etc. have a role to play.

[Harpy July 11, 2012 at 9:00 pm Post count: 184]

#1172857

Thanks Kimberly
I read some stuff on the Block & Replace a while back and from memory I think it may have been a combination of both dose levels as well as treatment period which may have contributed to the difference in results between the Japanese studies & elsewhere & as you say there may well be a genetic factor in racial origins as well.
I had a look at the study you posted and that definately seems to indicate an unknown beneficial factor in using Thyroxine supplementation in the final treatment stages of GD to further improve rates of remission. I haven’t read the full study, just the brief, but do wonder if the Thyroxine supplementation, which would naturally result in lowered TSH levels, hence reducing thyroid production of FT4 may simply allow the thyroid more healing time or if the Thyroxine itself has some other beneficial effect. I was aware of using thyroxine to better manage FT3 & FT4 levels, but this study suggests it could be used as an active part of the treatment protocol for GD.
http://www.nejm.org/doi/full/10.1056/NEJM199104043241403

To improve likelihood of lasting remission there seems to be a number of factors that may or may not be additive.
1/ Extended ATD treatment periods once FT3, FT4 & TSH levels have been stabilised.
2/ Add Back of Thyroxine as finishing process in treatment, as per outcomes of study in link above.
3/ Low TSH receptor antibody levels before withdrawal of ATD treatment, well within stated range.
4/ Personal changes, attitudes, employment, diet, lifestyle etc.

[Darcy43 July 12, 2012 at 8:46 am Post count: 125]

#1172858

thanks goodness you are back Harpy!!!!!!!! Great information. You were missed!!!! I was having withdrawals…

[KimberlyOnline Facilitator July 12, 2012 at 10:22 am Post count: 4294]

#1172859

Harpy wrote:

2/ Add Back of Thyroxine as finishing process in treatment, as per your study.

Hi Harpy – My point with that study, though, is that the results have never been able to be replicated in any other study. So I wouldn’t use that one study to advocate the use of Thyroxine as a factor in bringing on remission.

Just because a study hasn’t been replicated doesn’t mean it’s totally without merit…but it does cast some doubt on the findings.

Take care!

[Harpy July 13, 2012 at 1:25 am Post count: 184]

#1172860

Darcy43
Thanks for the generous comment, almost sent me to your “crying thread”.
Been a bit busy, you know how it is, life just doesn’t hesitate in getting in the way.

Kimberly
My appologies, I did not intend to suggest in any way this was your opinion, just going freehand and did not proof effectively, have gone back and edited the line to more effectively reflect it as an outcome of the study linked.

Kimberly wrote:

Harpy wrote:

2/ Add Back of Thyroxine as finishing process in treatment, as per your study.

Hi Harpy – My point with that study, though, is that the results have never been able to be replicated in any other study. So I wouldn’t use that one study to advocate the use of Thyroxine as a factor in bringing on remission.

Just because a study hasn’t been replicated doesn’t mean it’s totally without merit…but it does cast some doubt on the findings.

Take care!

[Harpy July 13, 2012 at 5:46 am Post count: 184]

#1172861

I’ve been doing a bit of reading through various studies on the topic of ATD treatment protocols including Block and Replace, although I can’t seem to locate the often quoted Japanese study, not sure if it actually is the one linked a couple of posts back. In regard to the replication of the Japanese study, other information I stumbled across indicated the Japanese protocol for B & R was generally 3-5 years treatment, whereas the attempted replications generally went from 6 months to 2 years, with a different dosing protocol, hardly what one would call a replication.
But it did take me across a lot of interesting related studies, although they were unable to replicate the results, generally only reporting remission rates of 50-60%, but what wasn’t reported in the headline, but buried within the paper was the inference of remission predictors. Most of the studies did do some review breakdown of the patients that relapsed vs remission and reported strong remission indicators, the main ones being:
The presence of normal TSH levels
Low (negative) TSH receptor antibody levels
Reduced or Normal Goitre size
Smoking was also noted in a couple.
I didn’t try to recalculate the remission rates when these factors were taken into account, but as a rough guess it was in the >80% catagory, which is much improved.

So therefore the often quoted rate of 50-60% remission rate does not take any of these factors into account and seeing as there is an overall reluctance of Endo’s to test for antibodies and the withdrawal of medication before TSH levels have been normalised, it seems that many Endo’s have not read any of these studies either.

The one below specifically looks at TSH receptor antibodies and reports a predictive factor of over 70% for remission
http://www.thyroid.jp/pdf/dr_prediction_of_Graves_remission.pdf

Along with the predictive factors reported in the studies there are likely others that could be assembled with a weighted scoring that Endo’s could use as an effective support tool in their management of GD and give their patients a much more accurate prognosis in both treatment protocol and decisions of when it would be appropriate to stop treatment to evaluate remission.

The one listed was relatively recent, 2006, whereas the majority of the other papers were generally around 15 years old and most had stated that more studies were needed to fully evaluate treatment protocols and the questions that surfaced in their own trials, particularly the predictive factors, this work does not seem to have been done yet as far as I am aware.

[James July 13, 2012 at 3:03 pm Post count: 115]

#1172862

Hi Harpy, nice to see you checking in once in a while and thanks for the information.

Much of what I’m reading here in the various studies (some of which look very familiar to me), is very much what I had experienced personally in my past days of GD treatment.

Particularly point #1 in your synopsis especially rang true, that is:

“Extend ATD treatment periods once FT3, FT4 and TSH levels have been stabilized”.

In my case it wasn’t until I steadfastly remained on ATD treatment (VERY small doses) for an extended period of time with stabilized levels (and we’re talking several years), that I finally could achieve a sustained remission without relapse. It does take much resolve to work through this process as it is considered long term, all done of course with a supportive Dr. onside.

Thanks again, your posting is a big re-affirmation for me.

James

[KimberlyOnline Facilitator July 13, 2012 at 5:46 pm Post count: 4294]

#1172863

Hi James – Always nice to see you posting! I still need to get your “green” facilitator status back…I have another message in to our tech expert to see if we can fix this.

The conference registration just went live…hope you can make it!

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