The Ultimate Guide to Thyroid Function Testing – Hypothyroidism Edition

 

Photo by Romain Vignes on Unsplash

I want the full thyroid panel.

This common statement is second only to “I want the natural thyroid hormone” as the most misguided request I receive.  The U.S. medical establishment has unintentionally cultivated a “more is better” expectation from our patients.  With the proliferation of evidence-based clinical practice guidelines in the Kingdom of Endocrinology, sage physicians have tried to rein in profligate ordering of unnecessary tests.  These doctors understand that more information does not always equal better outcomes.  Instead, more information often results in false positives – abnormal results that do not indicate a real clinical problem.  This leads to sending patients and their providers off on wild goose chases at best, and it leads to patient harm at worst.

Sadly, the horse has already exploded out of the barn with respect to thyroid testing, and that horse is still galloping across the plains of Nebraska*.  The thyroid is ripe for this sort of nonsense, because there are so many darn tests on the menu.  I’m here to emphatically state that you don’t need 90% of the stuff on that menu.

But I’m special.

No, you’re not.

But my naturopath told me I’m a non-converter.

No, you’re not a non-converter.  And I hate double negatives.

But I have inflammation, so we need to check all the thyroid antibody levels.

I don’t even know what you mean by “inflammation.”  And no.

With that preamble, I present to you: Thyroid Function Tests Demystified:  Hypothyroidism Edition.

The competence of your health care provider is inversely proportional to the number of thyroid tests she orders for you.

Said another way, your HCP probably has quacky tendencies if she orders more than 1-2 TFTs for you on a recurring basis.

When hypothyroidism is suspected, TSH (thyroid stimulating hormone) should be the initial screening test, period.

There are uncommon situations which probably don’t apply to you – remember, you are not special – in which the TSH is not an adequate screen for hypothyroidism (e.g. hypopituitarism and critical illness).  In the vast majority of situations, however, TSH is the best indicator of even the most subtle thyroid hormone abnormalities.

Remember Jeff Foxworthy’s You Might be a Redneck… routine?  Your thyroid provider might be a quack if…

The Laboratory she uses has redefined the upper limit of normal for TSH as 2.5 mIU/L.  Your provider is almost certainly a quack if she has crossed out the Lab’s standard upper limit of 4.0 – 5.5 and written in a value from 2.0 – 2.5.  While I agree that, as theTSH climbs into the upper half of the normal range, it could indicate early/mild hypothyroidism, I strongly reject the idea that we should automatically and thoughtlessly label hundreds of thousands more people as having a disease that they almost certainly do not have.  How the heck is that responsible practice of medicine?

Now, using TSH for monitoring thyroid hormone replacement therapy is a bit different.  I still maintain that the Lab’s reported upper limit of normal should be left unmolested at around 4.0.  Most patients will feel the same regardless of where their TSH is within the normal range.  However, there are many people on thyroid replacement who feel best with a TSH in the lower half of the normal range, and it is perfectly acceptable to aim for that, on a case-by-case basis.  It is not ok to claim that every hypothyroid person can only be considered adequately replaced once the TSH is in the lower half of the range.  In my experience, there are plenty of hypothyroid patients who feel better with a high-normal TSH; these patients would clearly be harmed by inappropriately lowering the upper limit of normal for TSH.

If the screening TSH is in the upper half of the normal range, in the presence of symptoms suggestive of hypothyroidism, then repeat the TSH and check a free T4 (FT4) and thyroperoxidase antibodies (TPO Abs).

One reason why the alt-thyroid cult – oops…uh…I mean – community has gained so much traction is because of click-baity headlines like “Why Your Normal Thyroid Numbers Don’t Tell the Whole Story.”  As a lot of quackery does, this starts with a kernel of truth, and then it devolves into histrionic idiocy.

It is true that a patient can have clinically meaningful hypothyroidism with a normal screening TSH.  However, when I see someone with a screening TSH value of 1.0 and a normal FT4, who has been started on thyroid hormone because of “symptoms,” I know that the train has gone off the rails.  Remember, for a small, linear drop in FT4, the TSH will increase exponentially.  Therefore, the TSH is an ultra-sensitive indicator of subtle thyroid hormone abnormalities.  If it is high-normal, with a normal FT4, then TPO Abs may be a useful tool in figuring out whether the symptoms are actually due to a thyroid problem.

TPO Abs are produced by the immune system, and they attack the thyroid, causing a destruction of its ability to make thyroid hormone.  The presence of TPO Abs in the blood does not mean that one has hypothyroidism; it does mean that one is at risk of developing hypothyroidism.  In the setting of a high-normal TSH, an elevated concentration of TPO Abs could indicate early hypothyroidism, and a trial of levothyroxine is reasonable.  While a negative TPO Ab test does not make it impossible to have hypothyroidism, it makes it less likely.

Other thyroid antibodies have no role in the diagnosis and management of hypothyroidism.

You may have seen the following tests on your lab reports in the past: thyroglobulin (anti-thyroid) antibodies, TSH receptor antibodies, or thyroid stimulating immunoglobulins.  While each of these tests has utility in the management of a thyroid disease, hypothyroidism is not that disease.

TPO Abs, once found to be elevated, never need to be checked again.

If I had a dollar for every patient I’ve seen who obsesses over the direction in which her TPO Abs are trending, I could buy a few rounds of $20 craft cocktails for all the patrons in one of those secret speak-easy joints in Manhattan – on a Saturday night.  Do you know how hard it is to reeducate someone whose naturopath has been insisting for years that their Hashimoto’s is still uncontrolled, because the TPO Abs are still elevated?  Very.  Very.  Hard.

TPO Abs are a diagnostic tool, usually used to help determine whether someone with a borderline high TSH (as above) has clinically meaningful hypothyroidism.  Because the thyroid continues to be present in the body after starting thyroid hormone replacement therapy, the immune system will continue to react against it.  That’s just the nature of an immune reaction – if something is in the body that the immune system doesn’t like, it will generate antibodies against that thing.  If you remove the offending antigen (the target of the immune reaction), then the immune system will stop reacting against it.  You want to see your TPO Abs drop to zero?  Go to a surgeon and have your thyroid removed.  I can’t imagine why in the world you would want to do that, but it’ll work to make your lab test look prettier.

But how else can I lower my TPO Ab level?

To be unambiguously clear, I do not care what your antibody level is.  Let’s focus on getting you on a thyroid replacement regimen that gets your TSH normal and stable, and gets you feeling better.

But my antibodies are still high!  You’re just treating the symptoms and not the disease!  Shouldn’t I avoid gluten and all cruciferous vegetables, take selenium, and get started on low-dose naltrexone?

You see what I’m dealing with?  It is often near-impossible to redirect someone once they become invested in that TPO Ab number.  Because I’ve built up a significant callous on my forehead from repeatedly banging it into my exam room wall over the years, I will try to redirect an insistent patient two or three times.  After that, I just have to change the subject and move on, or risk concussion.

T3 levels have no role in the management of hypothyroidism…

Unless you’re a doctor trying to prove to a patient that her heroic dose of pig thyroid is, indeed, resulting in abnormally high blood levels of T3.  As I’ve explained in a prior post, T3 levels in the blood do not necessarily reflect what’s happening in your tissues, with respect to the conversion of T4 to T3 by deiodinase enzymes.

But my T3 level is low!  That means I have Wilson’s Syndrome and I need to be put on T3…now!

This is the kind of logic that, in my experience, leads to naturopaths titrating the T3 dose to atrial fibrillation.  Once again, please read my prior post about this issue, then get back to me if you still have questions.

Forget you ever read about reverse T3, T0, T1, and T2.  End of story.

If you’re reading this site, it’s probably because you like to understand things – believe me, I get that.  I don’t ask for many favors, but I’m asking you to trust me this once…the above tests will add absolutely nothing to your medical care.  It is totally unnecessary to invest your ATP in figuring out how to use or interpret these tests.

TSH is the only test needed to guide thyroid hormone replacement therapy.

Remember the logarithmic change in TSH for a small, linear change in the T4 level?  For this reason, TSH is the only useful blood test for monitoring thyroid status on levothyroxine (+/- liothyronine).  If your TSH is high or low, but anywhere within spitting distance of the normal range, your FT4 level is almost guaranteed to be within  the normal range – therefore, the FT4 adds nothing useful to your management.

In the unlikely event that you are special, and you have a pituitary problem, TSH cannot be used to diagnose hypothyroidism or guide thyroid hormone replacement therapy.

In hypothyroidism resulting from pituitary disease, the screening TSH will be low or normal.  Once treated with thyroid hormone replacement, the TSH will usually be low.  This is actually incredibly important, but for just a small number of people.  Unfortunately, while many primary care providers know that TSH can’t be used in this situation, it is common for them to forget that the patient has secondary (also known as central) hypothyroidism – not surprising, given that the majority of their patients have garden-variety primary hypothyroidism.  This often results in the patient having her dose of levothyroxine lowered, because the low TSH is thought to indicate over-replacement with thyroid hormone.  While this would be correct management of primary hypothyroidism, it is incorrect in secondary hypothyroidism.

If you have this condition (please don’t ask me if you have it – if you have to ask, you probably don’t), I would recommend making sure that your doctor always monitors your FT4.  While some doctors also like to see the TSH, as it should be low if on a therapeutic dose of levothyroxine, the FT4 is the more helpful test.  Nonetheless, I sometimes find it challenging to optimize the levothyroxine dose, as different people seem to feel best with their FT4 in different portions of the normal range.  I have to rely more on symptoms to guide replacement therapy, which is even more problematic in patients with central – as opposed to primary – hypothyroidism.  Patients with central hypothyroidism are often on other hormone replacement therapies (hydrocortisone, testosterone/estrogen, growth hormone) as well, and these other therapies have equally poor (or worse) biomarkers, with respect to helping me determine the proper dose of the hormone.  As a result, it’s fairly easy to confuse the symptoms of one inadequately replaced hormone deficiency with another.

Summary

If I could send you off with a simple, take-home message, it’s that hypothyroidism just isn’t as complicated or esoteric as many of those ridiculous thyroid blogs would have you believe.  While I intend this post to be the “ultimate guide” to thyroid function testing in hypothyroidism, I suspect there are things I haven’t covered in which you’re interested.  Let me know in the comments below!

 

* Why Nebraska?  Seriously, have you guys every driven across that state?  It is flat in every direction, as far as the eye can see; I bet a horse could gallop in any given direction until dropping from dehydration and malnutrition.  If I had fallen asleep due to boredom, I probably could have woken an hour later to find myself still in my lane, pointed due west.

 

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12 Replies to “The Ultimate Guide to Thyroid Function Testing – Hypothyroidism Edition”

  1. I’m surprised you would suggest that it doesn’t matter if your antibody levels are trending up or down. Isn’t it true that elevated TPO antibodies increase the risk of miscarriage, goiter, nodules, developing a secondary autoimmune disease, and thyroid (and possibly other) cancer? Wouldn’t reducing the risk of the development of other diseases be a good reason to supplement with selenium? Please accept this as an honest question– my endocrinologist advises selenium supplementation, and my antibody levels have declined substantially over time, which seemed to coincide with the end of some of my weirder symptoms, such as Raynaud’s. It is my sincere wish to avoid any head-banging. 🙂

    Referencing these two articles:
    Fröhlich, E., Wahl, R. “Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases.” Frontiers in Immunology. 2017; 8: 521. Published online 2017 May 9.

    Kent, Athol. “Thyroid Antibodies Associated With Miscarriage and Preterm Birth.” Reviews in Obstetrics and Gynecology 4.3-4 (2011): 128–129. 2011.

    1. Fair question. However, the antibody levels themselves are merely a marker for thyroid autoimmunity. The antibodies are not known to directly cause anything other than destruction of the thyroid’s ability to make thyroid hormone. While one would think that lowering the TPO Abs would slow down the destruction of the thyroid, that is not the case (I will write a post about selenium, as this is where selenium comes in).

      Reducing the TPO Abs does not lower one’s risk of developing any other disease or condition, because that does not change the underlying fact that the person has an autoimmune predisposition. In addition, while there is evidence that taking levothyroxine reduces the risk of miscarriage in women with + TPO Abs, there is not evidence that lowering those Ab levels with selenium reduces the risk of miscarriage (though it may reduce the risk of postpartum thyroiditis – more to come in a post).

      1. I would love to know more about why lower antibody levels do not mean less destruction of the thyroid tissue, so I will look forward to your selenium post.

        I’d like to state again that I’m asking honestly here, but I am confused by this:

        >the antibody levels themselves are merely a marker for thyroid autoimmunity. The antibodies are not known to directly cause anything other than destruction of the thyroid’s ability to make thyroid hormone.

        You seem to be saying that antibodies are merely a marker, and then go on to point (correctly) out that they are the actual cause of the disease’s tissue damage. What does “merely” mean here? You seem to be saying that having autoimmune disease is the meaningful risk, and the quantity of antibodies is irrelevant. But since the cause of autoimmunity is essentially unknown, to me, personally, it seems reasonable to assume that if something is bringing down the level of anti-self antibodies, that is probably, at least, not a bad sign, and maybe means something good? Obviously, with this level of evidence, not a goal worth chasing with steroids or anything with serious side effects, but I mean, selenium, 200mcg a day? Why the hell not?

        I’m also feeling a need for a “citation needed” on this statement:

        >Reducing the TPO Abs does not lower one’s risk of developing any other disease or condition

        Has this actually been proven? I’m a layperson with access (through my spouse, who is a research scientist) to a lot of medical journals, and I have never been able to come up with anything that specifically analyzed the symptoms or outcomes of those with high antibody levels vs. low antibody levels. It’s one thing to say, “we don’t know if this occurs,” and another to say, “this doesn’t occur.”

        Similarly, when you say

        >there is not evidence that lowering those Ab levels with selenium reduces the risk of miscarriage

        I’m pretty confident that is because there haven’t been any studies on the effects of lowering TPO-antibody levels via selenium on pregnancy outcomes. There have only been a handful of studies on the effect of selenium on antibody levels, and the largest one had a treatment group of only what, 42? How many of those 42 could possibly have been pregnant?

        I can understand why, as a doctor, you would say, “Since I have no evidence that this helps, I’m not going to recommend it to my patients,” but I can also understand why a doctor would say, “I don’t know whether lowering antibody levels helps, but since the antibodies are the cause of tissue damage, and selenium has no meaningful side effects at the right dose, I will recommend this to my patients.” After all, doctors still prescribe cholesterol-lowering drugs to people with high cholesterol, even though it’s unclear whether lowering cholesterol by those means actually leads to better outcomes or not.

        And I want to present a patient’s point of view on this. When I was a kid, I read an article about cancer patients who were asked to imagine that their immune systems were attacking the cancer cells in a cowboys-and-Indians type scenario. When I learned that I had autoimmune disease, I had this picture in my mind of my T-cells attacking my own tissue in this way, and there is a kind of horror in that thought. And because of my unusual symptoms, I was already being sent through several specialists who were checking me for more anti-self antibodies. Thinking about getting those antibodies down was important to me because it bothered me that my body was being attacked. That’s a fairly natural and normal response, I think– wanting to minimize an attack on one’s body. No one wants to think about being gnawed upon by, or “encrusted with” lymphocytes.

        1. … Immediately after hitting reply, I remembered that I did once see a study that specifically analyzed the symptoms or outcomes of those with high antibody levels vs. low antibody levels– “Symptoms in Euthyroid Hashimoto’s Thyroiditis: Is There a Role for Autoimmunity Itself?” Angela Dardano, Laura Bazzzichi, Stefano Bombardieri, and Fabio Monzani (Thyroid, Volume 22, Number 3, 2012). But it seems to have the opposite conclusion to yours, that high antibody levels do correlate to a high symptom load. I get that this doesn’t prove that reducing antibody levels also reduces symptoms, though.

          1. Yes, I remember reading at least one or two articles in the past that suggested people with TPO Abs and a normal TSH may feel worse than people with negative TPO Abs and a normal TSH. However, the general impression of the Endo community is that the most likely of the possible explanations is: people with TPO Abs may have other – as yet undiagnosed – autoimmune disorders. If they have another autoimmune disorder that is brewing, but “subclinical,” this could account for why they feel worse. While this is just one potential explanation for the finding, it seems more plausible to me than that TPO Abs have some kind of direct effect on how people feel, independent of their effect on the thyroid. I believe that the “other autoimmune disorder” hypothesis would also explain why lowering the TPO Ab level makes no difference in how people feel, as long as we’ve gotten the thyroid hormone replacement regimen correct. But honestly, we just don’t know the answer.

        2. Hi Sadie,

          There have been studies showing that, although selenium decreases TPO Ab titers (which intuitively should make Hashimoto’s “better”), it does not decrease the thyroid hormone dose requirement in patients taking it. Unexpected result? Absolutely. It should work to decrease the need for thyroid hormone, but it just doesn’t. Maybe this is where low-dose naltrexone will ultimately prove its worth – who knows?

          As far as reducing TPO Abs, that has never been shown to affect the development of thyroid nodules, thyroid cancer, or autoimmune diseases of some other kind. That’s really my point in calling them a marker. Yes, they destroy the thyroid. Yes, there may be an increased risk of a thyroid nodule being cancerous if TPO Abs are positive. But there is no study I know of (and no pathophysiologic mechanism that really makes sense) that would clearly link the TPO Abs to these other conditions as a clear cause and effect. So lowering the Abs doesn’t change the association between TPO Abs and other conditions; it just makes the Ab number look better on paper.

          This is analogous to certain cardiovascular risk markers, which we can measure in the blood. Some of these markers, when elevated, are associated with an increased risk of heart attack. We can lower these markers with drugs. But lowering these markers has no impact on heart attack risk.

          I get that the concept of one’s body being attacked is disconcerting. All I’m saying is that, so far, lowering TPO Ab levels with selenium hasn’t seemed to do much good (with a few exceptions I’ll talk about in a post).

  2. Dear HD,

    I really enjoy reading your blog and your unique style of writing.
    As a person with Hashimoto’s, I’ve been specifically waiting for this topic to come up.
    Here in Australia, naturopaths and alternative therapies are widely popular and accepted as legitimate. I too was influenced, and believed that sugar, gluten and supplements played a huge role in the management of my disease. Thanks for taking the time to put the information out there. I use it to re-educate myself after years of spending money on quackery.

  3. Interesting. I wonder if you plan to expand on this topic for hyperthyroidism/Graves Disease. I’ve been led to believe that autoimmune antibodies will keep TSH suppressed even after T3 and T4 levels have stabilized on medication (methimazole.) It would be interesting to see your take. Thanks!

  4. Thank you for such a great post!

    I recently inherited a number of patients from a doctor who had left practice. Every single one of her patients with hypothyroidism was getting a TSH, free T4, TPO antibodies, T3 and reverse T3 every 6 months. Unbelievable.

    I don’t even think she was a quack- I just think she had no damn clue what she was doing.

  5. Thank you for this explanation. I moved and therefore changed GP’s, the old GP’s tested for TSH and T4, the new just test for TSH and I had wondered about that. However as I have more trust in the new GP’s for other reasons, and appointment lengths limit what one can discuss, I have never asked them about why. Your explanation confirms my impression that this practice is rather more ‘on the ball’ than the previous one.

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