When lab results for thyroid function come back as “normal,” it’s easy to assume that everything is functioning well. However, there are several different reasons these results can be misleading. Today we answer a listener question and discuss the various reasons why a “normal” lab result may not always mean optimal thyroid function.

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In this episode, we discuss:

  • TSH does not give you a complete picture
  • Free thyroid hormone
  • Antibodies and thyroid hypofunction
  • What lab ranges are used for thyroid testing
  • Goiters and iodine deficiency
  • Thyroid patterns that may not show up on standard lab tests
  • Thyroid physiology, proper assessment, and treatments

Show notes:

  • Five Thyroid Patterns that May Not Show Up on Standard Lab Tests
  • DUTCH test – offered by Precision Analytical

Chris Kresser:  Hey, everyone, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week I’m going to answer a listener question from Laura. Let’s give it a listen:

“Hi Chris. My name is Laura and I’m from Ireland. I have a question for you about goiters and thyroid function. Basically I’ve had a goiter for over 5 years now and I get blood tests every 6 to 12 months which show that my thyroid levels and thyroid antibodies are always within the normal range. I’ve had ultrasounds confirming that the goiter is normal. However I have every symptom of hypothyroidism. The most worrying aspect for me is how much the swelling of my goiter can vary from a day to day basis. So if I’m tired or particularly when I’m stressed, under any emotional kind of stress, my thyroid swells, it becomes inflamed, tender and red. There’s a throbbing sensation like a headache, but in my neck, and I will instantly get a headache. Normally if I get a headache or a migraine, I’ll check my thyroid first to see if it’s swollen more than usual. And I have no energy. And whenever my immune system is low or I’m sick, or I have a head cold or flu, it’s the same thing that occurs. But it’s just the fact that the swelling varies from day to day and I’m just at a loss to do, a loss at what to do with conventional medicine. I’m waiting 18 months for a referral. But I have no faith because every test is normal and they don’t seem to care to get to the root. And I just have no idea holistically what to do anymore. And I mean if it was just the goiter, if it didn’t have that swelling and inflammation on a daily, hourly basis, it wouldn’t be so disconcerting. It’s just the fact that I am struggling and I need help.”

Hey Laura, thanks so much for sending in your question. I’m really sorry to hear about your struggles. I imagine it’s extremely frustrating. This is a huge topic, so I’m going to break it into several questions in order to frame the discussion.

TSH does not give you a complete picture

So the first question here is do “normal” lab results always mean normal or optimal thyroid function? And the short answer to that question is no. So the first thing we need to look at is what is actually being tested. In many primary care environments, practitioners will only test TSH, or thyroid-stimulating hormone. And TSH is what is produced by the pituitary gland. It’s the signal that’s sent to the thyroid gland to tell it how much thyroid hormone to produce. And there’s no doubt that TSH is the most sensitive marker for assessing both hypothyroidism and hyperthyroidism. But there’s also no doubt that it doesn’t on its own give you a complete picture of what’s happening with the thyroid gland. So if all that’s being tested is TSH, you certainly cannot rule out problems with thyroid function on the basis of that result alone.

Some practitioners might also test total T4 in addition to TSH. Now, T4 is the main form of thyroid hormone that is actually manufactured or produced in the thyroid gland. I think about 92, 93 percent of the hormone produced by the thyroid gland is T4. The rest is T3. Now, T4 does give you an idea of how well the thyroid gland itself is functioning because if T4 is normal, then that tells you the thyroid is doing a pretty good job of what it normally should do, which is to produce T4. But as we’ll discuss a little bit later in the show, T4 alone, again, doesn’t give you a complete picture because T3 is the more metabolically active form of thyroid hormone and is more responsible for doing all the things that thyroid hormone does in the body. And even if T4 is sufficient, if the thyroid gland is producing enough T4, if that T4 isn’t getting converted into T3, which mostly happens elsewhere in the body—in the liver, in the gut, in the peripheral tissues—then that person can still suffer from hypothyroid symptoms. And that’s indeed a very common pattern that we see a lot.

So TSH and T4 is probably the second-most common group of tests that a conventional practitioner will run. Some might also add T3, which is a little bit better because then, as I mentioned, you get some information about whether T4 is being converted into T3. But even TSH, total T4, and total T3 are not sufficient. Because total T4 and total T3 refer to the form of thyroid hormone that is bound to a protein carrier. So, hormones are fat soluble, they’re not water soluble, and the blood is mostly water. Which means that in order for hormones to be transported around the body, they have to be attached to a protein carrier, thyroid-binding globulin being the main protein carrier for thyroid hormone. So the total T4 and total T3 measurements are looking at how much of this thyroid hormone that is bound to the protein carrier and can be circulated around the bloodstream there is. And that is important. It does tell you, in the case of total T4, how well the thyroid gland is functioning and is the best way to measure that. But the problem with only looking at total thyroid hormones, the protein-bound thyroid hormones, is that in order for a hormone to become metabolically active and bind to cellular receptors and perform its function, it has to be cleaved, or separated, from that protein carrier once it gets to its destination.

Free thyroid hormone

And we call this form of hormone that has been separated from the protein carrier free thyroid hormone, so free T4 or free T3. And the free T4 and free T3 measurements are actually a better way of assessing the amount of metabolically active thyroid hormone in the system. And that’s important to know because it’s possible and not uncommon to have normal amounts of total T4, total T3, but to have low amounts of free T4 and free T3. And what’s happening in that case is there is an excessive amount of the protein carrier of thyroid-binding globulin, and that’s leading to a lower-than-optimal amount of the free thyroid hormone. And as we’ll discuss later, that can be caused by things like excess estrogen.

The opposite can be true as well. There can be not enough thyroid-binding globulin and too much free thyroid hormone. But that would result more in hyperthyroidism, typically, and that’s less common and not what we’re talking about here. So I’ll leave that for another discussion. So I know that might’ve been a little bit complicated, but in order to understand what we’re going to talk about next, we needed to do that basic overview of thyroid physiology. And now you probably understand more about it than even some practitioners, which is often amazing to me because when you really do understand the physiology, you see how it makes sense to test for all of these things, TSH, T4, total T4, and total T3, and then free T4 and free T3 is really what gives you the most complete picture of what’s happening with thyroid function.

Antibodies and thyroid hypofunction

But then of course we have to talk about antibodies. The most common cause of thyroid hypofunction in the developed world is Hashimoto’s, which is an autoimmune disease that affects the thyroid gland, where the body attacks the thyroid gland and eventually decreases its ability to produce thyroid hormone. Unfortunately, in the conventional model, thyroid antibodies are rarely tested for, and that’s because if the antibody test is positive, it doesn’t really change their treatment. In the conventional model, the treatment for hypothyroidism is just to prescribe thyroid hormone regardless of what the cause is. And so, from their perspective, it doesn’t really matter if antibodies are positive or not because it’s not going to change the treatment protocol.

Certainly in conventional medicine, there are treatments for other autoimmune diseases like rheumatoid arthritis and multiple sclerosis. But since in the conventional model, all of those treatments are based around global immunosuppression, like using steroids to globally suppress the immune system and Hashimoto’s, and those treatments are known to have a lot of side effects and long-term complications and risks, the calculation with Hashimoto’s in the conventional model is because it’s not as serious an autoimmune disease as something like rheumatoid arthritis or lupus, the the risk-benefit analysis doesn’t come out in favor of using those steroids or other immunosuppressants. And so there is no treatment offered for the autoimmune component, and they just prescribe thyroid hormone. So the net result of all that is that thyroid antibodies are typically not tested for in the conventional model.

However, in Functional Medicine, we look at it differently. Functional Medicine, as I’m sure you know by now, is all about identifying and addressing the root cause of the problem rather than just suppressing symptoms. And in many cases of hypothyroidism, the root cause of the problem is not actually the thyroid gland malfunctioning. The thyroid gland malfunctioning is the symptom of the real problem or the root cause here, which is immune dysfunction, autoimmunity. So in Functional Medicine, we very much do want to know if there are antibodies being produced against the thyroid, because if there are, then our primary focus will actually not necessarily be on the thyroid itself. It will be on balancing and regulating the immune system so it stops attacking the thyroid gland. So this is why antibodies, thyroid antibodies, are part of my basic blood workup for new patients, and I believe they should be, especially for anybody who’s suffering from symptoms that could be associated with hypothyroidism.

What lab ranges are used for thyroid testing

Now the last thing to address here in this first question of whether “normal” labs always mean normal or optimal thyroid function is of course what ranges are being used. The conventional lab ranges are, in many cases, based on a sample of people that have received those tests, and then they simply make a bell curve of the results, and anyone who is in the middle of that bell curve is deemed as being normal. So it’s that these ranges are based on what the average values are in a population, rather than what the optimal values are. And let’s look at the potential problems with that approach. Just focusing on TSH, or thyroid-stimulating hormone, is an example. So the initial studies to determine the range for TSH were done in the Nurses’ Health Study, and so they looked at a bunch of nurses. They measured their TSH and they did take steps to try to exclude people that had already been diagnosed with hypothyroidism and already had abnormal TSH. And I believe they even assessed thyroid antibodies, which is a little surprising. But what they didn’t do is any ultrasound or other types of assessments to screen for people who did have hypothyroidism but hadn’t yet been diagnosed. And the number of people with hypothyroidism that don’t know that they have it is actually significantly higher than the number of people that have been diagnosed. And so those initial studies led to a TSH range of around 0.5 to 4.5, which is now the standard conventional range.

But there have been many, many studies published over the last 20 years that have been critical of those initial studies. And they have pointed out that there were likely many people included in that initial study, those initial studies, to determine the range that actually did have hypothyroidism, which would’ve skewed the “normal” range of TSH to be much higher than it should be. And in those subsequent studies where they did a much better job of eliminating people with hypothyroidism from the bell curve analysis, they found that for a person with no evidence of poor thyroid function of hypothyroidism, a normal TSH was more like 0.5 to maybe 2 or 2.5, depending on the studies that you look at. So that is a much tighter range than 0.5 to 4.5, and it means that if you’re going to your doctor and they’re using the conventional range, and your TSH is 4, they’re going to tell you that you have a normally functioning thyroid gland, when most of the evidence now suggests that that’s simply not the case. And your TSH of 4 is actually indicative of perhaps a mild hypothyroid state. So those are several of the reasons why we can’t assume that so-called normal thyroid lab results are in fact indicative of normal thyroid function or optimal thyroid function.

Goiters and iodine deficiency

So the second relevant question here for Laura is, what does a goiter typically indicate? So, there’s no disagreement or controversy here about Laura’s goiter with her doctors, and goiter is often visible. So this is not something that can be easily explained away. And goiter is not normal. It’s not normal physiology, so we know that that’s indicative of a problem. And we know from the research that in the developed world, the industrialized world, the number one cause of goiter is Hashimoto’s, the autoimmune condition I mentioned where the body attacks the thyroid gland. In the developing world, the number one cause is iodine deficiency. But in the developed world, it’s Hashimoto’s. And the number two cause in the developed world would be iodine deficiency for goiter.

Here’s the thing. Even if a patient has goiter and they have been tested for thyroid antibodies … Laura didn’t mention that in her question, so I’m not sure whether she has. Oh, actually she did, and she said her thyroid antibodies were always in the normal range. About 20 to 30 percent of patients with Hashimoto’s, according to the studies, never test positive for thyroid antibodies. And in their case, a diverse multinodular goiter that is evident on ultrasound may be the only sign that they have Hashimoto’s. And this is well documented in the scientific literature. It’s not understood clearly why they don’t test positive for antibodies. In some cases they may have a compromised Th2 antibody humoral immune system, so they just are not very good at producing antibodies, period. And that can be assessed by testing total immunoglobulin levels IgG, IgA, IgM and IgE. It’s a pretty simple lab test.

In other cases, it’s not clear, but it is pretty clear that that’s the case, 20 to 30 percent don’t test positive for antibodies even after multiple tests. But that doesn’t mean that they don’t have Hashimoto’s and that their thyroid function is not compromised. So iodine is, moving onto iodine, it’s the backbone of thyroid hormone and it’s obviously, for that reason, extremely crucial for thyroid function. And as I mentioned, it’s the number one cause of goiter in the developing world and the number two cause in the developed world. Now, rates of iodine deficiency have gone down a lot over the past 75 to 100 years. That was largely because of the iodization of salt. So iodine deficiency used to be very common, and that is why iodine was added to salt. And it was actually quite effective at addressing that problem.

However, people who are on … who favor healthier types of diets usually switch to sea salt, which I think overall is a good choice because sea salt is higher in trace minerals and other nutrients. But the problem with sea salt is that it does not contain meaningful levels of iodine. And there aren’t that many other sources of iodine in the diet. Dairy products are a decent source, not because they themselves contain a lot of iodine, but because the tanks that dairy products are stored in are cleaned typically with an iodophor, or iodine-based cleanser, and that iodine gets into the milk. Sea vegetables like kelp, arame, hijiki, wakame, etc., are very rich in iodine and are consumed in Asia, in Asian countries, but not very often in the West. And then some species of fish like cod are pretty good sources of iodine. So, if you take a person who’s on a healthy Paleo-style diet and they’re eating sea salt, they’re avoiding dairy, but they’re not incorporating sea vegetables into their diet, they very well may be iodine deficient.

So, to summarize this section, if you have a goiter it’s extremely likely that you have a thyroid problem regardless of what the labs are saying. And statistically speaking, you likely have either Hashimoto’s or iodine deficiency. Now of course, the caveat applies here. I’m answering a general question, Laura. I can’t diagnose you from a distance or provide any medical advice, and I’m really hopeful that you can find someone to work with that understands all of this stuff well and can give you the appropriate diagnosis and attention. The fact that your symptoms get worse with stress, Laura, is another clue, as stress is a notorious trigger for autoimmune conditions. And it also wouldn’t be surprising that your symptoms would be worse when you have a cold or a flu, since those are also immune challenges to an immune system that may already be challenged with an autoimmune condition, if that’s the case.

Thyroid patterns that may not show up on standard lab tests

So the third question to ask here, is it possible that the thyroid is malfunctioning and not functioning properly, even if the lab results are all normal? So even if you’ve gotten TSH, total T4 and T3, free T4 and free T3, thyroid antibodies, and all those results are normal, is it still possible that the thyroid may be malfunctioning? And, again, the short answer here is absolutely. Way back in 2010, eight years ago now, I wrote an article called Five Thyroid Patterns That May Not Show Up on Standard Lab Tests, and I’ll put a link to this in the show notes. I’m just going to very briefly summarize these patterns, and then you can go read about them if you’re interested.

Number one is hypothyroidism due to pituitary dysfunction. So sometimes that can lead to a low-normal TSH because that’s produced in the pituitary. And then maybe a low-normal T4 or T3, but all of those could be in the standard lab ranges, and perhaps even in the functional ranges, which are tighter than the standard lab ranges. But the patient can still be suffering from hypothyroid symptoms. And in that case, it may be due more to a problem in the pituitary than it is with the thyroid gland itself.

The second pattern is one I briefly mentioned earlier, which is under-conversion of T4 to T3. So, remember that T4 is not very metabolically active, and although it’s the main thyroid hormone that’s produced by the thyroid gland, it has to be converted to T3 in order to be metabolically active. And that happens in the gut and in the liver and in other peripheral tissues around the body, and it can be inhibited by inflammation, gut issues, and also nutrient deficiencies. 

The third pattern would be elevated thyroid-binding globulin. Again, I referred to this earlier, that’s the protein that carries the thyroid hormone around the blood. And some states like high estrogen, which could be related to birth control or hormone replacement therapy, can elevate thyroid-binding globulin, and then that can lead to low levels of free T4 or free T3, even if total T4 and total T3 are normal. And the free T4 or free T3 might actually just be low normal in that case and not out of the reference range.

Four is non-thyroidal illness syndrome. This is sometimes referred to as central hypothyroidism. Here the problem is low levels of TRH, or thyrotropin-releasing hormone, which is secreted by the hypothalamus in order to tell the pituitary how much TSH to produce. Which then, as I mentioned, in turn goes to the thyroid gland to tell it how much thyroid hormone to produce. And the causes of NTIS, or central hypothyroidism, include things like leptin resistance, insulin resistance, inflammation, and other non-thyroid-related causes, hence the name. Now as a quick side note, this number four is a little bit different than the number four in the article that I wrote 10 years ago. Things do change over time, so you won’t find more information about this here, but we’re going to be writing an article. I’m going to be publishing an article about it soon.

And then the fifth is thyroid resistance. So this is similar to insulin resistance or leptin resistance, which I’m sure you’ve heard of. This is when both the thyroid and the pituitary glands are functioning normally, but the thyroid hormone is not getting into the cell where it’s needed. The cellular receptors for thyroid hormone have become resistant to thyroid hormone in the same way that way that the cells for insulin can become resistant to insulin. So this can be caused by things like chronic stress and high cortisol levels, inflammation, high homocysteine, and other factors.

Lastly in this, at least for this question, I should mention that there are some new tests being investigated that identify thyroid dysfunction at an earlier stage than the current blood markers. One of them is the ratio of free cortisol to total or metabolized cortisol. And this, you can get this information from the DUTCH test, which is offered by Precision Analytical. It’s a great test that I’ve been doing for a few years now. And we will often see people with high free cortisol and then low total cortisol. And the reason for that is that thyroid hormone is required to metabolize cortisol.

So if you have high levels of free cortisol, but then low levels of total or metabolized cortisol,  that is a kind of indirect way of showing that the levels of thyroid hormone in the body are not optimal because that conversion is not being made. So it’s not measuring thyroid hormone directly; it’s measuring something that depends on the action of thyroid hormone. And sometimes those indirect markers can actually be more sensitive in that they can identify problems that happened early on, even before the blood markers would go out of range. And I actually have seen that to be true in several cases in my clinical practice.

Thyroid physiology, proper assessment, and treatments

Okay, so what to do about all this? Well, again, it’s very tricky, especially for patients that are in a place that don’t have access, where they don’t have access to a Functional Medicine practitioner or that’s just not accessible to them for other reasons. But if it all possible, Laura, I would, it would be awesome if you could find a Functional Medicine practitioner to work with who is familiar with thyroid physiology and proper assessment of these issues and is willing to perhaps treat you. Do a therapeutic trial of a range of treatments for autoimmune under the assumption that you may have an autoimmune thyroid condition and see how you respond. Sometimes that’s the best way to do it in the absence of any conclusive information. And again, please understand that this is not medical advice. And I would definitely recommend finding someone local in your area to work with, if at all possible.

But there are also some steps you can take yourself, even if you can’t find someone to work with, under the presumption that it may be autoimmune. One is to try the autoimmune Paleo diet, autoimmune protocol diet, AIP, as it’s known. I don’t believe that everyone with an autoimmune condition needs to be on that forever. But I do think that everyone should try it at least once if they haven’t tried it already. It can make a really big difference because diet, even foods that are healthy otherwise for people without autoimmune conditions, can trigger immune dysfunction in a subset of people who have autoimmunity. So that would be step one, for sure. And there are a lot of resources online and books that you can find, that can help you to get on that diet successfully.

Then there are things like optimizing vitamin D status, optimizing glutathione status, because both of them are T regulatory cell, they both help with T regulatory cell production and differentiation. And those are the cells that help balance and regulate the immune system. Likewise, curcumin is an anti-inflammatory that has an immunoregulatory effect. Low-dose naltrexone is something interesting to explore. I’ve written some articles about that and have done podcasts about that in the past. It helps to balance and regulate the immune system, and it reduces central nervous system inflammation.

And actually, there is a pretty well-known doctor in Ireland, I think in Dublin. I could be wrong about that, but somewhere in Ireland named Dr. Phil Boyle. And he is very experienced with low-dose naltrexone, been a proponent of it for a long time, and he’s used it in, he primarily, I think, has a fertility clinic and helps women to get pregnant and uses low-dose naltrexone to do that. But as far … he may also treat other conditions. I’m not sure. You may want to consider contacting him. And then stress management. I can’t emphasize how important that is. I can’t emphasize enough how important that is for autoimmune conditions. It’s just absolutely crucial.

Okay, so I hope that was really helpful. I hope this gives you some food for thought and some things to try. I know we haven’t been doing a lot of these Q&A episodes lately, but please do keep sending your questions to ChrisKresser.com/podcastquestion. Even though we’re not able to answer all of them, they do inform my thought process about what articles to write and material to cover, even outside of the podcasts. So please do keep them coming. Thanks, everybody, for listening, and I will talk to you soon.

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Source: Chriskresser