Guest guest Posted May 9, 2003 Report Share Posted May 9, 2003 Hi Devin, Your doctor must have missed the articles showing that the presence of TSH receptor antibodies, which are increased after RAI, cause TSH to be suppressed. The pituitary has TSH receptors that recognize these antibodies as if they were TSH. Thinking there is enough TSH to regulate thyroid hormone levels, the pituitary stops secreting TSH. The initial report was described in 2001 by the world's top thyroidologists WM Wiersinga and MF Prummel. The article, Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary receptor. Journal Clinical Endocrinology and Metabolism 2001;86:4814-4817. In December 02, Dr. Utiger described this study on the Thyroid Foundation of America. The original article states that it's well known that it takes a long time for TSH to return to the normal range. I'm not sure where she got her 8 month timeframe, but many people do not secrete TSH until they become hypothyroid. You should be able to get the original article through Pub Med. Take care, Elaine Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 9, 2003 Report Share Posted May 9, 2003 Hi Devin- I'll have to admit your plots confused me (everything confuses me with this postpartum brain). But it doesn't matter. If your TSH is rising that should be a good sign for the endo. Especially if your FT3 and FT4 are within the normal range. I know of no study that gives a time limit for low TSH so you might ask her to produce one for you so you know it's not just her whimsical cut-off time. There are some studies that show osteoporosis related to subclinical hyperthyroidism but they don't refer to how long the patient has been that way. I'm with Elaine. Pull the study she referenced and show it to the endo on your next visit. There's no need to subject yourself to a 2nd round of RAI and being isolated from your family if it's not necessary. Take care, dx & RAI 1987 (at age 24) > I had a meeting with my endo yesterday. During the last meeting she was pushing for a second dose of radioiodine. I refused in light of my hormone trends, which had peaked and where now dropping. At that time, she argued that it had been nearly 6 months and I was still high (barely) in FT3 and high within normal for FT4 (her " normal " being defined as the reference range). I argued that it didn't matter, as my levels were trending down towards the reference range - no matter how slowly. The meeting concluded with an uneasy wait and see agreement. > > The next four test results (roughly monthly) have all my FT4 results in the reference range, ending mid-range and my FT3 results dropping into the reference range - though admittedly ending high in the range. > > I expected these results to be very pleasing to my endo., even if imperfect. But all she could focus on was the TSH which has only increased from undetectable (<0.02) to 0.03 (reference range 0.34-5.6 ). She steadfastly insisted that the TSH should be normal 8 months after RIA. She claimed since it wasn't, it was an indication that my body wants my FT3 & FT4 levels to be lower - even if they have to be suppressed well below the reference range in order to get the TSH to rise - the means: more RIA (i.e. permanent). My first response was that this was clearly crazy. She claimed that that leaving the TSH repressed for much longer would lead to irreversible heart and bone damage. I still refused - largely out of confusion. She said that if the TSH isn't up by our next appointment, regardless of the FT3 and/or FT4 levels, she will refuse to treat me any longer (which means refuse to prescribe any more blood tests). > > So what do you all think? Is there some basis for being greatly concerned if the TSH level fails to renormalizing soon after the free hormone levels reach the reference range via RIA? > > Hopefully the following " plots " will survive font changes and still look as intended. The " I " s are the reference range bounds, the " O " s are test results (with a bit of rounding to match increments). Right is increasing levels, and down is increasing time. The time of RIA is indicated by a labeled dashed line. > > > > > > Low Reference High > > ----I---------I-O---------- > > ----I---------I-------O---- > > --- I - - - - I - - - - - - - RIA > > ----I---------I------O----- > > ----I---------I---------O-- > > ----I---------I--O--------- F > > ----I-------O-I------------ T > > ----I-------O-I------------ 4 > > ----I----O----I------------ > > ----I-----O---I------------ > > > > > > > > Low Reference High > > --- I - - - I - - - - - - - - - RIA > > ----I-------I----O----------- > > ----I-------I--------------O- > > ----I-------I----O----------- > > ----I-------IO--------------- F > > ----I-------O---------------- T > > ----I-------IO--------------- 3 > > ----I-----O-I---------------- > > ----I------OI---------------- > > > Thanks, Devin Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 10, 2003 Report Share Posted May 10, 2003 It would seem you are referring to: " Suppression of Serum TSH by Graves' Ig: Evidence for a Functional Pituitary TSH Receptor " by Brokken LJ, Scheenhart JW, Wiersinga WM, Prummel MF Received April 2, 2001. Accepted June 12, 2001. Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 10 4814-4817 I must be missing a piece. This entire article seems to deal with chemical suppression of the thyroid. Is it somehow implied that a similar effect would occur if the thyroid is damaged by RIA? Devin Re: TSH Renormalization > Hi Devin, > Your doctor must have missed the articles showing that the presence of TSH > receptor antibodies, which are increased after RAI, cause TSH to be > suppressed. The pituitary has TSH receptors that recognize these antibodies > as if they were TSH. Thinking there is enough TSH to regulate thyroid hormone > levels, the pituitary stops secreting TSH. The initial report was described > in 2001 by the world's top thyroidologists WM Wiersinga and MF Prummel. The > article, Suppression of serum TSH by Graves' Ig: evidence for a functional > pituitary receptor. Journal Clinical Endocrinology and Metabolism > 2001;86:4814-4817. > In December 02, Dr. Utiger described this study on the Thyroid > Foundation of America. The original article states that it's well known that > it takes a long time for TSH to return to the normal range. I'm not sure > where she got her 8 month timeframe, but many people do not secrete TSH until > they become hypothyroid. You should be able to get the original article > through Pub Med. Take care, Elaine > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 10, 2003 Report Share Posted May 10, 2003 Devin, The point isn't that of chemical suppression. The point is that RAI stimulates the immune system and increases the production of TSH receptor antibodies, both stimulating and blocking ones. TSH receptor antibodies are recognized by the pituitary as if they were TSH, similar to the way thryoid cells do. Thus, thinking there is adequate TSH to regulate thryoid hormone levels, the pituitary doesn't secrete TSH. After RAI, it can take quite some time for TSH to rise. Take care, Elaine Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 11, 2003 Report Share Posted May 11, 2003 -----BEGIN PGP SIGNED MESSAGE----- Hash: SHA1 vze47vfr wrote: > It would seem you are referring to: > > " Suppression of Serum TSH by Graves' Ig: Evidence for a Functional Pituitary > TSH Receptor " > by Brokken LJ, Scheenhart JW, Wiersinga WM, Prummel MF > Received April 2, 2001. > Accepted June 12, 2001. > Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 10 4814-4817 > > I must be missing a piece. This entire article seems to deal with chemical > suppression of the thyroid. Is it somehow implied that a similar effect > would occur if the thyroid is damaged by RIA? Hi Devin, how are you feeling? !!!!!!!!!!!!!!!! If it is the paper Elaine discussed with me before then it refers to an effect that is also demonstrated in thyroidectomised rats. Human immunoglobulin from Graves patients reduces TSH in the absence of a thyroid implies that it is not stimulation of the thyroid, but the feedback mechanisms that regulate thyroid hormone production are directly affected by the presence of the antibodies. The doctors assume this means the pituitary can detect TSH, thus it must have TSH receptors and is thus presumably responding to TSH receptor antibodies (since these are known to occur in the blood of Graves patients and not in control group). Lot of assumptions in there, lets take the engineering perspective -- Graves blood into rat, rat's pituitary produces less TSH, ergo we assume your pituitary may also be underproducing -- ignore the speculation as to why it might happen. I think it is fairly compelling evidence that Graves patients shouldn't assume TSH is representative. Quite why doctors always assume that the thyroid regulation mechanisms are perfectly calibrated the instance things start getting closer to normal has always made me wonder, I think they just learn to trust TSH in treating hypothyroidism, and would feel lost if they couldn't. I certainly would run from an endo who would suppress free hormone levels below reference ranges, just to get the TSH right, been there with antithyroid drugs and got rid of that doctor. As Dr Toft famously said " you don't feel TSH " , the implication being you may well feel fT3 (although in my experience if fT3 is suppressed you don't feel much, mostly cold and depressed, and my skin goes slightly numb like it doesn't quite belong to me). My endo is quite clear, he states 'the goal of treatment is normalisation of fT3'. Your fT3 is normalised, hopefully your feeling about right. Normalisation of TSH can wait, let's label it " nice to have " . There is the unanswered question of whether having this part of the HPA suppressed might affect other endocrine processes, but the main one we know much about is lactation, and I hope you aren't doing much of that. Haven't managed to get a properly documented distribution for fT3, but my experience is that most people are in the upper part of the range, probably for the same reasons that the TSH test has recently had it's upper limit reduced. i.e. there are a lot of borderline hypothyroid people included in these ranges. Renormalisation would be Devin TSH, in Devin TSH units, giving the answer 1, or did I do too much theoretical physics Even if you aren't happy with the current levels of thyroid hormone, I'm sure you've read plenty on the long term effects of radioactive Iodine, and realise that a further trend to hypothyroidism can occur long after the I-131 has decayed away. Your plots didn't confuse me, but is the scale linear, and is the recent increase in fT3 within the range of error of the tests/diagramming used? Numbers have there place as well. -----BEGIN PGP SIGNATURE----- Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org iD8DBQE+vne/GFXfHI9FVgYRAg6oAKCSvd9yAdWiAa+dS1K+b4+faGWMJQCePhAl WlLrOkqJLkTbcZLyYuIcP44= =Wnnu -----END PGP SIGNATURE----- Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 12, 2003 Report Share Posted May 12, 2003 Simon Is it a given that TSH antibodies are produced post-RIA (or produced in untreated Graves victims)? If so, is there a test to measure their level? To the degree allowed by a hundred pixels, the plot scales are simple linear/linear. The 2000 X 2000 pixel plot looks little different, provides no additional data, and can't be posted on group emails. To within the apparent accuracy the measurement, there is no rise in hormone levels following the initial peak several months after RIA, just variations within the established error. These doctors seem fixated on the boundary of the reference range even though it's just a statistical construct. A reading a little below and all is fine - a reading a little above and all is wrong - unless they are trying to meet some other goal, then even being in the middle of the reference range isn't worth anything - it's inconstantly maddening. To make sense of imperfect tests and results, one must set an objective - a goal. In your case it's normal FT3 levels. In my doctor's case it's getting my TSH into the reference range. I think my doctor is using the wrong goal, and I would like to support this belief, or be convinced to change my viewpoint. Devin Re: TSH Renormalization > -----BEGIN PGP SIGNED MESSAGE----- > Hash: SHA1 > > vze47vfr wrote: > > It would seem you are referring to: > > > > " Suppression of Serum TSH by Graves' Ig: Evidence for a Functional > Pituitary > > TSH Receptor " > > by Brokken LJ, Scheenhart JW, Wiersinga WM, Prummel MF > > Received April 2, 2001. > > Accepted June 12, 2001. > > Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 10 4814-4817 > > > > I must be missing a piece. This entire article seems to deal with > chemical > > suppression of the thyroid. Is it somehow implied that a similar effect > > would occur if the thyroid is damaged by RIA? > > Hi Devin, > > how are you feeling? !!!!!!!!!!!!!!!! > > If it is the paper Elaine discussed with me before then it refers to an > effect that is also demonstrated in thyroidectomised rats. Human > immunoglobulin from Graves patients reduces TSH in the absence of a > thyroid implies that it is not stimulation of the thyroid, but the > feedback mechanisms that regulate thyroid hormone production are > directly affected by the presence of the antibodies. > > The doctors assume this means the pituitary can detect TSH, thus it must > have TSH receptors and is thus presumably responding to TSH receptor > antibodies (since these are known to occur in the blood of Graves > patients and not in control group). Lot of assumptions in there, lets > take the engineering perspective -- Graves blood into rat, rat's > pituitary produces less TSH, ergo we assume your pituitary may also be > underproducing -- ignore the speculation as to why it might happen. > > I think it is fairly compelling evidence that Graves patients shouldn't > assume TSH is representative. Quite why doctors always assume that the > thyroid regulation mechanisms are perfectly calibrated the instance > things start getting closer to normal has always made me wonder, I think > they just learn to trust TSH in treating hypothyroidism, and would > feel lost if they couldn't. > > I certainly would run from an endo who would suppress free hormone > levels below reference ranges, just to get the TSH right, been there > with antithyroid drugs and got rid of that doctor. As Dr Toft famously > said " you don't feel TSH " , the implication being you may well feel fT3 > (although in my experience if fT3 is suppressed you don't feel much, > mostly cold and depressed, and my skin goes slightly numb like it > doesn't quite belong to me). > > My endo is quite clear, he states 'the goal of treatment is > normalisation of fT3'. Your fT3 is normalised, hopefully your feeling > about right. Normalisation of TSH can wait, let's label it " nice to > have " . There is the unanswered question of whether having this part of > the HPA suppressed might affect other endocrine processes, but the main > one we know much about is lactation, and I hope you aren't doing much of > that. > > Haven't managed to get a properly documented distribution for fT3, but > my experience is that most people are in the upper part of the range, > probably for the same reasons that the TSH test has recently had it's > upper limit reduced. i.e. there are a lot of borderline hypothyroid > people included in these ranges. > > Renormalisation would be Devin TSH, in Devin TSH units, giving the > answer 1, or did I do too much theoretical physics > > Even if you aren't happy with the current levels of thyroid hormone, I'm > sure you've read plenty on the long term effects of radioactive Iodine, > and realise that a further trend to hypothyroidism can occur long after > the I-131 has decayed away. > > Your plots didn't confuse me, but is the scale linear, and is the recent > increase in fT3 within the range of error of the tests/diagramming used? > Numbers have there place as well. > -----BEGIN PGP SIGNATURE----- > Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org > > iD8DBQE+vne/GFXfHI9FVgYRAg6oAKCSvd9yAdWiAa+dS1K+b4+faGWMJQCePhAl > WlLrOkqJLkTbcZLyYuIcP44= > =Wnnu > -----END PGP SIGNATURE----- > > > ------------------------------------- > The Graves' list is intended for informational purposes only and is not intended to replace expert medical care. > Please consult your doctor before changing or trying new treatments. > ---------------------------------------- > DISCLAIMER > > Advertisments placed on this yahoo groups list do not have the endorsement of > the listowner. I have no input as to what ads are attached to emails. > -------------------------------------------------------------------------- ------------ > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 12, 2003 Report Share Posted May 12, 2003 Devin - I don't know if this will help your case any or not, but there is another article from JCEM that discusses TSH antibodies and TSH suppression. The reference is Journal of Clinical Endocrinology and Metabolism Vol. 85 Num. 11 (November 2000) and the article is titled " Expression of the Thyroid-Stimulating Hormone Receptor in the Folliculo-Stellate Cells of the Human Anterior Pituitary " . Some of the work from the April 2001 article references this earlier work. Basically, the article discusses the finding of a TSH receptor (TSH-R) on the Folliculo-Stellate cells in the anterior pituitary gland. They talk about how the finding of this TSH-R suggests that the TSH-R antibodies " act as a ligand for the pituitary receptor and cause suppression of the TSH secretion " . and because the TSH-R antibodies can remain present for a long time, this may be the cause of long term TSH suppression. I believe this is what they went on to prove in the April 2001 article. The other interesting little piece of info that came out of this study was that they found that the TSH-R in not only found on the thyroid gland. it says, " However, it has now become clear that the TSH-R is also functionally expressed in other extrathyroidal tissues. For example, the TSH-R was also found to be expressed on intestinal T cells, where it is involved in local paracrine regulation of T cell homeostasis by sensing locally produced TSH. " So since RAI doesn't do anything to eliminate the antibodies responsible, it seems entirely reasonable that you still have circulating TSH receptor antibodies that are mucking around with the TSH production. There are tests for the different types of TSH receptor antibodies (TRAb). Our ever popular TSI are the stumilating type TRAb. The blocking type TRAb are the ones found mainly in Hashimoto's. Then there is the binding type TRAb, usually called thyrotropin-binding inhibitory immunoglobulins (TBII). They interfere with the binding of the TSH to the receptor. I agree, it does sound like doc is concentrating on the wrong goal (had one of those myself, it is enough to make you wish you had a medical degree!) If you could get him to run antibody levels and they came back high, hopefully he would see the case for waiting to see if the TSH comes back up. Good luck! Re: TSH Renormalization > > > > -----BEGIN PGP SIGNED MESSAGE----- > > Hash: SHA1 > > > > vze47vfr wrote: > > > It would seem you are referring to: > > > > > > " Suppression of Serum TSH by Graves' Ig: Evidence for a Functional > > Pituitary > > > TSH Receptor " > > > by Brokken LJ, Scheenhart JW, Wiersinga WM, Prummel MF > > > Received April 2, 2001. > > > Accepted June 12, 2001. > > > Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 10 4814-4817 > > > > > > I must be missing a piece. This entire article seems to deal with > > chemical > > > suppression of the thyroid. Is it somehow implied that a similar effect > > > would occur if the thyroid is damaged by RIA? > > > > Hi Devin, > > > > how are you feeling? !!!!!!!!!!!!!!!! > > > > If it is the paper Elaine discussed with me before then it refers to an > > effect that is also demonstrated in thyroidectomised rats. Human > > immunoglobulin from Graves patients reduces TSH in the absence of a > > thyroid implies that it is not stimulation of the thyroid, but the > > feedback mechanisms that regulate thyroid hormone production are > > directly affected by the presence of the antibodies. > > > > The doctors assume this means the pituitary can detect TSH, thus it must > > have TSH receptors and is thus presumably responding to TSH receptor > > antibodies (since these are known to occur in the blood of Graves > > patients and not in control group). Lot of assumptions in there, lets > > take the engineering perspective -- Graves blood into rat, rat's > > pituitary produces less TSH, ergo we assume your pituitary may also be > > underproducing -- ignore the speculation as to why it might happen. > > > > I think it is fairly compelling evidence that Graves patients shouldn't > > assume TSH is representative. Quite why doctors always assume that the > > thyroid regulation mechanisms are perfectly calibrated the instance > > things start getting closer to normal has always made me wonder, I think > > they just learn to trust TSH in treating hypothyroidism, and would > > feel lost if they couldn't. > > > > I certainly would run from an endo who would suppress free hormone > > levels below reference ranges, just to get the TSH right, been there > > with antithyroid drugs and got rid of that doctor. As Dr Toft famously > > said " you don't feel TSH " , the implication being you may well feel fT3 > > (although in my experience if fT3 is suppressed you don't feel much, > > mostly cold and depressed, and my skin goes slightly numb like it > > doesn't quite belong to me). > > > > My endo is quite clear, he states 'the goal of treatment is > > normalisation of fT3'. Your fT3 is normalised, hopefully your feeling > > about right. Normalisation of TSH can wait, let's label it " nice to > > have " . There is the unanswered question of whether having this part of > > the HPA suppressed might affect other endocrine processes, but the main > > one we know much about is lactation, and I hope you aren't doing much of > > that. > > > > Haven't managed to get a properly documented distribution for fT3, but > > my experience is that most people are in the upper part of the range, > > probably for the same reasons that the TSH test has recently had it's > > upper limit reduced. i.e. there are a lot of borderline hypothyroid > > people included in these ranges. > > > > Renormalisation would be Devin TSH, in Devin TSH units, giving the > > answer 1, or did I do too much theoretical physics > > > > Even if you aren't happy with the current levels of thyroid hormone, I'm > > sure you've read plenty on the long term effects of radioactive Iodine, > > and realise that a further trend to hypothyroidism can occur long after > > the I-131 has decayed away. > > > > Your plots didn't confuse me, but is the scale linear, and is the recent > > increase in fT3 within the range of error of the tests/diagramming used? > > Numbers have there place as well. > > -----BEGIN PGP SIGNATURE----- > > Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org > > > > iD8DBQE+vne/GFXfHI9FVgYRAg6oAKCSvd9yAdWiAa+dS1K+b4+faGWMJQCePhAl > > WlLrOkqJLkTbcZLyYuIcP44= > > =Wnnu > > -----END PGP SIGNATURE----- > > > > > > ------------------------------------- > > The Graves' list is intended for informational purposes only and is not > intended to replace expert medical care. > > Please consult your doctor before changing or trying new treatments. > > ---------------------------------------- > > DISCLAIMER > > > > Advertisments placed on this yahoo groups list do not have the endorsement > of > > the listowner. I have no input as to what ads are attached to emails. > > -------------------------------------------------------------------------- > ------------ > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted May 12, 2003 Report Share Posted May 12, 2003 -----BEGIN PGP SIGNED MESSAGE----- Hash: SHA1 vze47vfr wrote: > > Is it a given that TSH antibodies are produced post-RIA (or produced in > untreated Graves victims)? If so, is there a test to measure their level? The papers I've seen didn't demonstrate the cause as one specific antigen in Graves blood altering TSH production. The assumption is it would be the TSH receptor antibodies, these are produced in Graves patients, but the levels are known to rise very quickly after RAI treatment, and stay raised on average for nearly two years. These are probably responsible for the increase/worsening of Graves opthalmopathy following RAI. Here the test is called a " TSH receptor antibody test " , Elaine says it is more usually referred to as a " TSI test " in the USA. > These doctors seem fixated on the boundary of the reference range even > though it's just a statistical construct. Tell me about it, they all need a crash course in non-parametric statistics. > In your case it's normal FT3 levels. Alas they seem to have pulled their local thyroid advice website. Rats, probably me pointing out the advice from the endocrinologists, wasn't consistent with the pathology provided to patients by the pathology lab, much cheaper to can the website than actually treat people correctly. The Prodigy system (advice for UK GP's) notes the goal as treatment as " normalising fT4, and eventually TSH " . Although I did ask in my usual diplomatic way whether the goal of treatment should be making patients better*. http://www.wretched.demon.co.uk/UKthyroidlinks.html follow Prodigy for hyperthyroidism, it isn't great, it does reference the literature for most things. www.thyroidmanager.org site notes that TSH can lag the patient status. They advise against repeating RAI within 6 months because it is possible things haven't settled. > In my doctor's case it's getting my TSH into > the reference range. I think my doctor is using the wrong goal, and I would > like to support this belief, or be convinced to change my viewpoint. I agree with you, from what you've said so far. Although I think the ultimate goal has to be subjective quality of life measure, the intermediate goal should be normalising serum free hormone measures. TSH is too slow, and has too many question marks about it. The lag of TSH is better documented than the suppression through antibodies, so if you want something scientific to convince your doc follow that route in the research. Or at least ask to wait 6 months from normalising the serum free hormone levels, before discussing more treatment. But at the end of the day, it is your consent that is needed, although I appreciate it can create problems if you withhold it without giving reasons. I have similar problems getting a rational basis for my treatment, despite my best efforts, and my doctor agreeing to start from a publish framework for antithyroid drug treatment, I can't get the blood work done to properly support the protocol. I can only conclude they prefer medicine to remain an art, not a science. Simon *Hence the question " how are you feeling? " , which you skipped. I'm feeling lousy today, but my TSH was " normal " last week so it is obviously all in my head, although interesting only a fifth as much TSH as there was last month. -----BEGIN PGP SIGNATURE----- Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org iD8DBQE+v8PMGFXfHI9FVgYRArlvAJ0dshb85fwBMC4Sfvby7WG92B7rwQCeJYbx crpyri1BqwGXHf9QhSnbwKA= =nT65 -----END PGP SIGNATURE----- Quote Link to comment Share on other sites More sharing options...
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