Thyroid dysfunction is not that uncommon these days with more and more people being put on thyroid medication for either low or high functioning thyroid activity. This could be in the form of inactive T4 thyroid hormone (Levothyroxine, Synthroid), active T3 hormone (Cytomel, Triostat) or a combination of both (Thyrolar).
It can even come from a natural glandular source usually derived from pig thyroid glands.
But is medicating always the only or even final answer?
We don’t believe so.
Not when we consider that most thyroid dysregulation is usually secondary in response to some other biochemical imbalance in the body as oppose to something being physically wrong with the thyroid gland itself. Off course there are exceptions to this.
SECONDARY vs PRIMARY THYROID DYSFUNCTION
Many other health challenges can cause fluctuations in TSH (Thyroid Stimulating Hormone) levels which is the thyroid marker most tested for by mainstream medicine, even though this is not a thyroid hormone in the true sense of the word.
Some of these ‘thyroid influencers’ include:
- Chronic infections
- Chronic stress
- Nutritional deficiencies
- Sleep disturbances
- Ketogenic diets
- Long term fasting
- Gastrointestinal disorders
- Sluggish gallbladder
All of these ‘influencers’ can have a secondary effect on thyroid function which may make it more challenging to balance thyroid function without addressing these influencers first.
We could even argue that thyroid disorders associated with antibodies is more of a secondary thyroid dysfunction rather than primary, because we still have to find the root cause for antibody production. Your body doesn’t just one day decide to make antibodies against your thyroid, or any other organ for that matter.
It isn’t genetic. It isn’t just being unlucky. It is in fact environmental.
Environmental may mean diet, lifestyle, the type of work you do, the place where you live, the people you surround yourself with, the toxins you are exposed to, etc.
But let’s not get too ahead of ourselves. What we really need to discuss is why some people are put on thyroid medication but don’t respond appropriately.
Let’s start with the easiest ones first…
POOR GUT ABSORPTION OF THYROID MEDICATION
Thyroid medication has to be taken on an empty stomach about 30 – 60 minutes before breakfast, or 3 or more hours after dinner. Taking it too close to meals or snacks can reduce absorption by up to 64%, and even up to 80% when you’re fasting.
This is according to the American Thyroid Association.
STORING YOUR THYROID MEDICATION IN THE WRONG PLACE
It seems like such a simple thing but it’s important to store your medication in a cool, dry, dark place. Exposing pills to excess heat, light, and moisture can make your thyroid medication less effective.
Don’t store it in wet areas such as bathroom cabinets or close to heaters. If you live in hot climates such as Australia then it may be best to store it in the fridge. Always follow the directions on the label.
These are the most common reasons. What are the more complex issues surrounding the effectiveness of thyroid medication?
WHEN REVERSE T3 INCREASES INSTEAD
Some individuals who take T3 hormone may find that their free T3 levels remain unchanged but that their reverse T3 (rT3) levels increase instead when taking or increasing their medication. It is generally considered that rT3 is ‘bad’ but it is in fact a compensatory mechanism that the body employs when it doesn’t want or need any more active T3 hormone.
Once active T3 levels go over the optimal levels for that person at that point in time the body will convert active T3 to inactive rT3, no matter how much hormones you take. This is typically what happens when cortisol levels start to increase. Cortisol is another stimulatory steroid hormone that is released in response to starvation, stress, over-training and infections. Having both high cortisol and high active T3 will result in extreme over-stimulation that may make you more anxious, interfere with your sleep, or result in heart palpitations.
Reducing active T3 by converting it to rT3 is your body’s way of settling things down a bit.
This is where you need to investigate why you may have high cortisol levels. Possible reasons include:
- Emotional stress from family, work, relationships, trauma.
- Physical stress from over-training or not sleeping enough.
- Inflammation from infections, over-training or eating a nutrient-poor diet.
CELLULAR ABSORPTION OF ACTIVE T3
Cellular absorption of active thyroid hormone may also be a factor. In these instances you are likely to see your blood thyroid hormone levels increase but not feel the effect.
Your body needs it, so it’s not converting active T3 to inactive rT3. But because it is not being absorbed into the cells for whatever reason it starts to accumulate in the blood instead as free T3 hormone.
The challenge here is that most practitioners will simply consider that you are taking too much of the thyroid medication and start reducing the dosage. In a way this is both right and wrong. It certainly doesn’t help taking large amounts of medication if it’s not getting to where it needs to in order to do its job. But just cutting medication without looking at poor cellular absorption as a possible factor also isn’t going to help you feel any better.
Either way, you still end up feeling exactly the same.
Possible reasons for poor cellular absorption include:
- Damaged or unhealthy cell membranes
- Impaired methylation
- Oxidative stress
- Toxin exposure
THYROID RECEPTOR RESISTANCE
Now let’s say that you are taking your T3 medication, blood levels look good all around, but you still don’t feel better and there doesn’t seem to be any explanation that can be seen from your blood test results.
What does this mean?
It may indicate that active T3 is getting into the cells, but not actually working. To explain this better, let’s first look at receptors inside the cell.
TR/RXR Heterodimer Complexes
Inside cells you have thyroid hormone receptors (TR) and retinoid x receptors (RXR) which is a nuclear receptor. RXR binds to TR to form a complex called a heterodimer which is essentially when two large molecules bind together to form one large complex or a super receptor. Whenever RXR binds to another receptor it amplifies the action of that receptor, so in this case it amplifies the function of the thyroid receptor and thus the action of thyroid hormones.
Once active T3 hormone enters the cell and binds to the thyroid hormone receptor (TR) part of this TR/RXR heterodimer complex inside the nucleus of the cell. This heterodimer complex then interacts with DNA sequences and alters the ability to make certain proteins. Active T3 has to be able to bind to TR and the whole complex has to work to interact with DNA.
This is how active T3 and thyroid hormones in general are able to control processes such as metabolism, development and growth, and also why healthy thyroid function during pregnancy is so important. The developing foetus is solely dependent on the mother’s thyroid hormones for all of these activities to take place.
Nutrients needed in TR/RXR Heterodimer Complex
But off course if we don’t support this system it may not work as well as it should.
How do we do this?
Vitamin A in the form of 9-cis retinoic acid acts as a ligand for RXR’s. In other words, we need vitamin A to make this receptor work. Vitamin A is also a fat-soluble vitamin which means we need bile to absorb vitamin A into the bloodstream and thus healthy gallbladder function. Having a sluggish gallbladder or having had your gallbladder removed can certainly impact on vitamin A absorption, the function of RXR and thus also the ability for thyroid hormones to do their job.
Zinc is another very important mineral. Zinc is necessary for everything that has a nuclear receptor that alters gene expression. This means zinc is necessary for the function of RXR and TR, but also other nuclear receptors such as VDR (vitamin D receptor) and nuclear sex hormone receptors.
This illustrates how nutrient deficiencies and gallbladder dysfunction may play a role in thyroid hormone receptor resistance where there are enough active thyroid hormones but just an inability to do its job.
Possible reasons for vitamin A and zinc deficiency include:
- Gallbladder dysfunction or removal
- BCMO1 gene polymorphisms that are being expressed
- Gut dysbiosis
FREE FATTY ACIDS AND THYROID FUNCTION
While we’re on zinc deficiency, it has also been implicated in a build up of free fatty acids (FFA’s) which can be measured through an NEFA (non-esterified fatty acids) test. You’ll see why this is important.
Insulin Resistance (IR) will tend to upregulate lipoprotein lipase (LPL) and in this way increase the production of FFA’s. Remember that IR can be triggered by stress, oxidative stress, inflammation, and off course poor lifestyle and dietary choices.
Eating a lot of fat will also upregulate LPL and increase the production of FFA’s.
But, as long as these FFA’s are able to cross the cell membrane and be burned up for fuel, such as during exercise, it is not a problem. So for instance, someone who is following a high fat, low carbohydrate ketogenic diet and exercises will burn up these FFA’s. Because there isn’t enough glucose available for the increased exercise activity, cells will register this as ‘cellular starvation’ which means it will allow more FFA’s into the cell to be used for fuel instead as oppposed to accumulating in the bloodstream.
Eating a diet high in carbohydrates and sugars on the other hand will prevent FFA’s from entering the cell and being burned up for fuel. This is because the cell will already be saturated with glucose and pyruvate from carbohydrates and thus will have plenty of fuel. In fact, probably too much! The cell doesn’t want any more energy, so it downregulates the CPT1 transporter needed to get FFA’s into the cell. So FFA’s have to stay outside and wait their turn until all the sugar inside the cell has been burned off.
This doesn’t mean that starving yourself is any better. If you starve yourself through prolonged fasting or if you suffer from eating disorders, LPL will also be upregulated in order to try and liberate fats into FFA’s for fuel for the cells (since you are not eating any glucose or carbohydrates). Doing this long term may induce hepatic insulin resistance and also affect healthy function of the liver with consequences for detoxification and sex hormone detoxification. This may give rise to other issues such as estrogen dominance and / or PCOS (polycystic ovarian syndrome) in females.
So, what happens if FFA’s are allowed to accumulate? Why is this important?
If FFA’s are allowed to build up due to any of the reasons mentioned above it can inhibit or prevent T4 (inactive thyroid hormone) from binding to its carrier proteins such as TBG (thyroid binding globulin). This can lead to acute increases of free T4 and a decrease in total T4 concentrations which is how too much FFA’s can suppress thyroid function independent of the amount of thyroid hormones you have in your blood.
This is another example of how blood thyroid markers may seem normal, but you display symptoms of low thyroid function. We sometimes call this Functional Hypothyroidism.
Sometimes there is an easy explanation of why your thyroid medications are not reducing your thyroid-related symptoms, such as poor storage or bad timing of taking your medication.
Other times the reasons can be more biochemical and these are often missed by even the most seasoned practitioners. Make sure you don’t have any nutritional deficiencies and that your diet and lifestyle is supporting a healthy thyroid function.
Always keep in mind that most thyroid dysregulation is secondary, so even if you are taking thyroid medication it is still important to address anything else that may be causing this dysregulation. Whatever caused your thyroid issues in the first place is still going on somewhere inside your body and is likely to affect other hormonal systems as time goes on, irrespective of the fact that you are taking thyroid medication.
Most importantly, work with someone who you trust will listen to you and your reactions to your medications. Someone who is treating you and not a number on a test result.