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Thyroid UK
90,433 members • 104,800 posts

Thyroid-Stimulating Hormone

Why Efforts to Harmonize Testing Are Critical to Patient Care

I had added this to another post and I'm afraid it got lost. There are some interesting statements in this article that Thyroid Patients should be aware of. PR

"Based on the functional interrelationship of the hypothalamus, pituitary gland, and thyroid, TSH should be elevated if the thyroid gland is not producing adequate thyroid hormone, and suppressed if it is producing too much (Figure 1). Today, however, we are beginning to realize that this well-established paradigm for TSH synthesis and release is an oversimplification."

"Although laboratory measurement of serum TSH is an essential tool for diagnosing and managing various thyroid disorders, the laboratory medicine community has long recognized that immunoassays used to measure the hormone are yet another source of variability in patients’ results."

"The upper limit of euthyroidism with first-generation TSH assays was approximately 10 mIU/L, but with the introduction of second- and third-generation assays it fell to approximately 5 mIU/L. The most likely reason for this change was the reduced cross-reactivity afforded by the monoclonal antibodies used in the newer assays."

"there is growing consensus that one TSH reference interval does not fit all."

aacc.org/publications/cln/a...

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PR4Now, I'll have to read it again as I got a bit lost but am I right in saying that this moves us closer to what Diogenes said, that TSH is individual?

thyroiduk.org.uk/tuk/TUK_PD...

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Clutter, that is a good question, hopefully Diogenes will add his insight. It sounds like it to me but without talking to Dr. Thienpont, which is unlikely, I wouldn't want to say that is a given. But at least Dr. Thienpont is acknowledging some pertinent points.

The TFTs will still suffer from a 'low index of individuality' which was partially acknowledged by the statement "individuals appear to have their own set-points, and factors such as race and age also contribute to variability in TSH levels." There have been six studies that I know of regarding the 'low index of individuality' of the TFTs, the first in 1986. The underpinning work on this goes back to the 1950s, at least. The most often quoted study is Anderson et al. from 2002. He measured 16 healthy individuals once a month for 12 months and plotted their own individual 95% reference range for the TSH, TT4, TT3 and FTI. One was excluded because it was thought he suffered from mild hyperthyroidism. The width of the individual Reference Ranges for TSH for the remaining 15 varied from 0.32--2.35 units wide, with the average being 1.13 units wide. Because we all have our own unique individual set point, based on our genetics, epigenetics and metagenomics, each persons' set point was slightly different. The group RR was 0.16-2.39 uU/mL. So if you are an individual with a narrow 95% RR and a low set point you could move 2 or 3 full points and still be in the "normal" range. You don't show up on the Thyroid Function Tests until the extremes. They are anything but 'highly accurate' for an individual, at best they are a rough clue. They know there is a ballpark but they have absolutely no idea where home plate is for any given patient. What science doesn't have any understanding of is how far do you have to move off your own set point to cause problems. Dr. Anderson thought a move of 0.75 was significant. As we have discussed previously, many of us feel that the longer it takes to get adequate treatment the more damage that can be caused, quite often changing a person's own set point.

This is a short presentation from 2003. You have to use a PC and you have to use IE. If it doesn't start right away, it takes a minute or so to start. It is only about 17 minutes. They also knew the FT3 test was a mess back then, it wasn't a secret. PR

site.blueskybroadcast.com/C...

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i remember reading somewhere - cant remember where - of a large study in turkey that positively sought healthy and no family history of anything metabolic that found it was just under 1 for tsh. this seemed supported by my frien who recently had tsh test as tired and hers was 1.0 - she had low iron that was her health problem that was easily resolved with supplements. what about this research anyone else know of it?

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Generally speaking, the mean for the TSH is usually between 1.0 and 1.5 in many studies. This can vary due to iodine and/or selenium deficiency, race/ethnicity and somewhat by age. Other factors like low iron, B12, folate, Vit D, Cortisol, stress, diet, environmental toxicity and autoimmunity can affect individuals just like your friend whose TSH was 1.0 and yet she was tired because of low iron. I also suspect that thyroid hormone resistance is more prevalent then commonly recognized. PR

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I have a hunch that having a pituitary that doesn't put out quite as much TSH (and possibly, other hormones) as would appear appropriate is another major issue. Not talking about it being so severe as to call it hypopituitary - just that when it perhaps "should" be pumping out enough to get a TSH reading of, say, 10, it is only ever reaching 5. Possibly in the range up to, pick a number from the air, 3.0, it is fine, but it won't go much higher.

Rod

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Rod, thanks for adding that. AS often as it is mentioned here you would think I would have remembered that point. PR

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The TSH test was invented to support the use of synthetic T4 and is at best useless.

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Quite a lot of the earliest mentions of TSH available at least in abstract on PubMed discuss distinguishing primary from secondary myxoedema and nothing to do with synthetic levothyroxine.

Whilst I do not think that TSH is the right way of testing thyroid patients, in my own case, TSH level has actually closely approximated to my own feeling. But being tested once a year is hardly an adequate regime for overseeing our well-being.

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Glynisrose, even with all its shortcomings I actually think it can be a useful test but only if you understand its limitations. The TSH test was discovered in the continual quest to understand the endocrine system. Science is a moving target of discovery, rarely does it have all the answers at any given point in time. PR

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The problem is that there are doctors aged from their mid 20s up to retirement age and beyond who have been taught that TSH measurement is the best thing ever invented for monitoring thyroid disease. It is going to be very, very hard (I think impossible) to change their minds, particularly since they are being asked by researchers to start believing something more complicated than their current beliefs. Nobody likes letting go of simple ideas. Also there is a never-ending fight back against change from the drug companies who are making billions from levothyroxine and treatment of all the side effects of untreated, under-treated and incorrectly treated thyroid disease.

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humanbean, I agree it will be difficult to change the paradigm and introduce 'personalized medicine' where the patient is part of the equation but I'm already seeing cracks in the wall here in the US. We have ended up with a health care system that neither the patients nor the doctors are happy with. Patients are abandoning allopathic medicine in droves because they aren't getting results and doctors are moving to functional, integrative, anti-aging, holistic and CAM because they are tired of being pill dispensers which is not how they want to practice medicine. The next several years will be interesting times to say the least. PR

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Both Faix and Linda Thienpont have corresponded with me through email and both are rare beasts if I may put it this way: that is levelheaded and analytical rather than the many unthinking boneheads that exist in medicine. If you want a paper that Rudolf Hoermann and I discussed the role of TSH as a personal diagnostic rather than a "blanket" one by simply applying the "reference range" then go to:

TSH Measurement and Its Implications for Personalised Clinical Decision-Making.

Rudolf Hoermann, John E M Midgley

Journal of thyroid research. 01/2012; 2012:438037.

This is an open access journal, so no difficulty in downloading. There we say exactly what we both think about the use of TSH.

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This makes my reference a little bit easier to access:

TSH Measurement and Its Implications for Personalised Clinical Decision-Making, Rudolf Hoermann and John E. M. Midgley

Volume 2012 (2012), Article ID 438037, 9 pages

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hindawi.com/journals/jtr/20...

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Diogenes, a technical question on a different point. When they make synthetic thyroxine don't they make both the dextro and levo form and then they have to remove the dextro form? I'm sure you have noticed all the posts about the reactions people have to various brands. This is usually put down to the fillers and binders but I wonder sometimes if there isn't a problem with contamination from the dextro form. The process to make levo-thyroxine is something I have little understanding of. PR

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If I have understood this patent document at all, I think not:

google.com/patents/US2579668

And this patent specifically identifies reduced D- form as an aim of their process:

google.com/patents/WO200913...

So I heartily endorse the concept of contaminants. I always wonder about breakdown products of the levothyroxine.

Rod

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Rod,

"Where the group R is the group which group contains an asymmetric carbon atom, we have found that the use of optically active starting material leads to the formation of an optically active product. This fact is of use in the synthesis of L-thyroxine which compound is of greater physiological activity than D-thyroxine."

I think this may be pertinent but without a chemistry background I need the "Chemistry for Dummies" version to understand it. PR

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Or diogenes! :-)

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Rod, I have to admit that he does have a good knack for simplifying the complex for people like me that are lacking the appropriate background. PR

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L-thyroxine (without the D form) has been produced from L-tyrosine by a chemical synthesis eg in:

The synthesis of thyroxine and related substances. Part V. A synthesis of L-thyroxine from L-tyrosine

J. R. Chalmers, G. T. Dickson, J. Elks and B. A. Hems

J. Chem. Soc., 1949, 3424-3433

Nowadays as above no D-L separation is necessary so long as you start with an L-form of a precursor like tyrosine. Only if you start with a D/L mix of tyrosine will you get D/L thyroxine.

Hope you found my paper as listed here of use re TSH and individual set points.

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Diogenes, thanks for the clarification, I can understand what you wrote about the precursor. I've read your paper before, a couple of times, but I will go read it again. Each time I read it I gain a little more understanding. First however I have to go pick up leaves, we are having a sunny 50 F degree day and it looks like it will be the last of the season. We have been 20-30 degrees below average for the last 2 weeks and the fall cleanup season got shortened considerably compared to a normal month. PR

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Just a little bit more on what D- and L- isomers of compounds mean. A central carbon atom in a compound has four binding bonds which it can bind to other molecules and atoms. The bonds in 3 dimensions are distributed like the corners of a pyramid with a triangular base and the C atom in the middle. Now lets call the base corners A, B and C representing different groups and D a group stuck to the bond stuck up in the air to form the apex of the pyramid. Now lets compare two molecules, one with A to the left corner of the base and B to the right, and the other with B to the left and A to the right. Putting the two face to face you will see they are mirror images of each other. These are the stereoisomers. If you make crystals of each purified and shine a kind of light called polarized light through the crystals, then one form will twist the light to the left (laevo-L) and the other to the right (dextro-D). And that is how you can test the purity. If there is some D in the L prep then the light isn't twisted as much as it should be, because the D is trying to twist the light back to the right. So this light twisting on a product is a very accurate way of testing purity of L-thyroxine for example and absence of D contaminant. That's stereochemistry in as few words as I can muster.

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Diogenes, thanks for that. That brings up another question but I need to finish rereading your article first. PR

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