On the day that Dr Toft tells the Scottish Parliament that TSH maybe isn't 100% perfect, a paper which expressly investigates one reason that may be the case.

Although we think of TSH as being a single substance - that isn't quite true. It comes in slightly different variations - called isoforms. They have different extra bits attached - that is, they have differing glycosylation. It is a bit like a bakery turning out bread, croissants and iced buns - simply by adding butter or sugar to a basic flour, yeast and water. Although similar, we are all aware of their differences.

If the measurement of TSH in a test and its biological activity are always exactly the same, then there would be no problem. But from what I can see, that seems not always to be the case.

As so very often, nothing much available except the abstract...

Thyroid. 2013 Sep 27. [Epub ahead of print]


Estrada JM, Buckey TM, Burman KD, Soldin OP.


Georgetown University Medical Center, Department of Oncology, Washington, District of Columbia, United States ;


Serum thyrotropin (thyroid stimulating hormone, TSH) is often the test of choice for the screening, diagnosis and monitoring of primary hypothyroidism. In the general population, serum TSH is considered the single most sensitive and specific measure of thyroid function owing to its negative logarithmic association with free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. Serum TSH concentrations can be analyzed quantitatively using third generation immunoassays, whereas TSH bioactivity can be assessed using assays that measure TSH activity in cell culture. Theoretically, if serum TSH concentrations are directly related to TSH activity, the two tests should yield comparable results. However, on occasion, the results are discordant; serum concentrations being higher in comparison to the biological activity of that TSH. This review focuses on the dissociation between the clinical state and serum TSH concentrations and addresses clinically important aspects of TSH analysis.

PMID: 24073798 [PubMed - as supplied by publisher]


7 Replies

  • Interesting! I'm almost up to reading the whole paper. I shall give it a shot tomorrow :)

  • I hadn't even thought of this effect. How interesting, as Toft and Williams said we are still learning. On my reading list for tomorrow. Thank you!

  • Will any notice be taken of this Research. Can someone notify the Scottish Parliament?

    I have heard a particular specialist called an 'eejit' (Scottish for idiot) which word could be applied to all the Specialists who appear not to listen or read and take note of Research. Neither do they listen to the suffering patients.

  • This effect has been known for some time, but has not been quantified quite as well as this. The problem is that TSH assays from different manufacturers will recognize different isoforms of TSH with different efficiency, so that the indicated readings on a given sample may significantly differ between tests. Obviously this impinges on diagnosis. Note how the authors still go on about the log TSH-FT4/3 relationship to justify TSH. The US is still miles behind the times in this regard and this general paradigm has to be squashed before real universal progress can be made, because it is only true in hypo and hyper states and changes to no relation at the borderlines in normality.

  • Thank you diogenes.

    Is it believed that the various isoforms have different biological effects?

    I have long wondered if the different isoforms affect anything like the T4:T3 ratio produced by the thyroid or the rate of conversion of T4 elsewhere?


  • Yes the isoforms have as stated in the paper, different potencies re stimulation of the thyroid. In nonthyroidal systemic illness, isoforms are rife. I think the effect on the thyroid gland is really only the effective action of the particular TSH form and doesn't control T4/3 ratio production (but that's my guess, not gospel). That is if say 100 units of TSH in active form 1 have a given effect on the thyroid, then 80 units of different TSH with active form 1.25 would have the same overall effect. That's my reading of it, but nature is often more subtle than any of us can imagine. So don't be surprised if I'm wrong there. Because I'm assuming TSH is a generalized activator whatever its potency.

  • Thanks, Rod, interesting - I tried the link top right, and it came up as an error.

    Is this paper available free? You said the abstract was all that was available.


You may also like...