A couple years ago (end of 2013) the reference range for TPO antibodies (TPOAb) was <35 IU/ml but now it's <9 IU/ml. That's a huge change (almost 4x). Does anyone know why it changed by so much and if somewhere between 9 and 35 is actually not that bad?

1 Answer 1


Reference ranges vary by labs. In some assays, 35 IU/mL is still considered the upper limit of normal. The reason for the dramatic difference in reference ranges is the detection limit of the assay itself. As time progresses, assays become more sensitive to small titers of antibody. In labs using newer techniques, concentrations as low as 9 IU/mL can be detected, so anything above that is considered abnormal.*

The question of whether an antibody concentration between 9 and 35 IU/mL is as detrimental as a higher concentration is an interesting one. First, in way of background for those not familiar with anti-TPO antibodies: these are antibodies directed against the thyroid gland. They are most often measured in a patient with “subclinical” hypothyroidism (i.e. elevated TSH but normal free T4). In such cases they have been shown to be prognostic for progression to overt hypothyroidism.2

As it turns out, there is evidence1 that the titer of antibody within the range you ask about affects prognosis. The linked study used an assay detecting levels as low as 5.5 IU/mL. Those who spontaneously improved had a mean TPO titer that was significantly lower than the group that progressed to overt hypothyroidism requiring thyroid replacement (13.85 IU/mL vs 39.9 IU/mL, p= 0.028). Note that the mean in the spontaneously improving group would have been considered “less than assay” in a test with a detection limit of 35 IU/mL.

So yes, “somewhere between 9 and 35 IU/mL is actually not that bad”, if “bad” refers to a titer greater than 35 IU/mL and the relative prognostic value is of interest.

* Many lab tests have a lower limit of detection within the physiologic range like this. These tend to be looking for antibodies or enzymes that are not supposed to be present at a detectable level. In such cases the “normal” result is “LTA = less than assay”. As lab tests get better and that detection limit goes lower, more people end up characterized as “abnormal”. Such is scientific progress.

1. Myung Won Lee, Dong Yeob Shin, Kwang Joon Kim, Sena Hwang, and Eun Jig Lee, The Biochemical Prognostic Factors of Subclinical Hypothyroidism. Endocrinol Metab. 2014 Jun; 29(2): 154–162.

2. Vahab Fatourechi, Subclinical Hypothyroidism: An Update for Primary Care Physicians. Mayo Clin Proc. 2009 Jan; 84(1): 65–71.

  • On a lab result it said the detected amount was 13 but the reference range was <35 IU/mL. Does this mean that maybe there's some other explanation for the change in reference range? Thanks
    – g491
    Commented Oct 9, 2015 at 4:46
  • A bit confused: didn’t your question say that the reference range was <9 IU/mL in the result you were looking at? I’m not sure I follow your question in the comment about the change in reference range - from what to what (if not 35 to 9 as stated in the original question)?
    – Susan
    Commented Oct 9, 2015 at 5:07
  • There were two results - in one the ref range was <9 and the other the ref range was <35. But the measured value (which I didn't post in my original question) was 13 for the ones that had the ref range of <35 . Thx
    – g491
    Commented Oct 9, 2015 at 5:11
  • Ah, I see what you’re saying. I think it’s just people choosing the degree of badness of prognosis they consider “abnormal”. The higher the titer, the higher the likelihood of progression to overt hypothyroidism. The values between 9 and 35 are indeed associated with increased risk compared to undetectable, but there’s not a way to represent with a normal/abnormal dichotomy the fact that lower is still better than higher within the detectable range. This is why continuous variables are more informative. :-)
    – Susan
    Commented Oct 9, 2015 at 5:16

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