Making sense and optimising your thyroid lab results

For better health, metabolism and longevity

Taking control of your health can feel overwhelming, with so much information out there these days. It has become easier to be healthy, with more nutritious food options available, friends and partners jumping on the train too, so you aren’t the odd one out. But with that also can come overwhelm and not knowing where to start, what is legit, and what overhyped ***. And how do you know you are doing it right?

In this series I will take you through some commonly tested lab markers, that you likely had done at one of your GP visits/ annual check ups. Most likely (or hopefully), the labs came back as ‘fine’ — and your GP sent you home saying there is nothing to worry.

But did you know that common lab reference ranges are based on the average of the population, not necessarily on optimally healthy people? It is no surprise then, that people commonly are ‘fine’ on labs for decades, only to be hit with a disease diagnosis ‘overnight’. Well, that’s where the differentiation between ‘normal’ and ‘optimal’ lab ranges comes into play.

Often markers, while in ‘normal’ range, are outside the ‘optimal’ range for a long time, gradually contributing to micro damage, and ‘sludge’ building up in our intricate body machinery. If enough of this ‘sludge’ or ‘rust’ builds up, eventually the coghweels grind to a halt — and a disease, and alarm stage is reached. It is generally then that regular labs pick up on the problem.

Why not take control of your health years earlier and address subtle imbalances before they turn into a real problem? With Functional Medicine and a root cause approach, we can, even when there is already a proper problem, slowly unwind the root causes to give the body the chance to heal. However, that process can be tedious, slow (and sometimes near impossible, if they entire cogwheel machinery of our body has properly seized up and a lot of damage has occurred).

With this blog post series, I want to empower you to be proactive, and address subtle imbalances and keep the ‘cogwheel machinery’ of the body running as smoothly as possible, to prevent that seized up, alarm stage from happening, by looking at where things can be optimised.

And by knowing what is going on inside the body, you can still choose to ‘live a little’ (after all, what would be the point of a zero fun life, overly obsessing about health which secretes stress hormones that damage us anyhow), by making educated choices, supporting your body’s pathways, while potentially here and then doing things that aren’t entirely ‘perfect’ — ie it is fine to have those fries once a week, or perhaps one too many glasses of red or a late night with in adequate sleep — as long as it is in moderation, and balanced out by nourishing choices most of the time.

In today’s post I was going to write about thyroid hormones, so let’s get to that. We will start with the basics, so you get a better understanding of why certain factors matter, then dive into why you want to optimise those levels, and what ranges to aim for, if you want to keep everything running as smooth as possible inside your body, to look and feel better, for longer.

https://www.youtube.com/watch?v=CCcrV4I_48M

An introduction to thyroid function

You likely have had a TSH test done at some point over the years. TSH is short for thyroid stimulating hormone and is produced in the brain. It sends signals to the thyroid gland located in the throat to make the actual thyroid hormones, T3 and T4. Most of the thyroid hormone produced by the thyroid is in the precursor form, called T4. Only some of the active form, T3, is made in the thyroid itself. Most of the active thyroid hormone T3 is being produced outside the thyroid, throughout the body (‘peripherally’), by conversion of the precursor T4 to the active hormone T3, such as in the liver and kidneys. This is done by enzymes called deiodinase D1 and D2. A different version of the deiodinase enzymes, D3, breaks down and inactivates the thyroid hormones (R).

Most of those hormones are in fact bound, and as such not available to do their job. Only a tiny fraction is free and ready to do the jobs we expect thyroid hormones to do. They are the ‘free T4’ and ‘free T3’. With the ‘free T3’ being the main one.

What thyroid hormones are needed for

A properly functioning thyroid is important for many functions in the body, including:

• Metabolism
• Energy
• Heart rate
• Healthy cholesterol levels
• Mental and brain health
• Bone health
• Fertility
• And many other functions (R).

Most common symptoms associated with a sluggish thyroid

Many know thyroid hormones mainly for their role in metabolism and weight regulation, as a sluggish thyroid can make it much harder to loose weight. Some of the most common symptoms associated with a sluggish thyroid, also called ‘hypothyroidism’, (often linked to the autoimmune condition ‘Hashimoto’s thyroiditis’) include:

• Weight gain
• Elevated cholesterol levels
• Fatigue
• Depression (R)
• Hair Loss
• Cold sensitivity
• Insulin resistance and with it a reduced carb tolerance
• Difficulties conceiving.

Most common symptoms associated with an overreactive thyroid

On the contrary, an overactive thyroid, ‘hyperthyroidism’ (often linked to the autoimmune condition ‘Grave’s disease) can produce symptoms such as

• Sweating
• Arrhythmia (irregular heartbeat)
• Weight loss
• Protruding eyes
• Nervousness (R)

The thyroid — sex hormone and fertility connection

Thyroid hormones also have knock on effects on sex hormones, such as progesterone and estrogen, contributing to menstrual cycle issues such as PMS, perimenopause chaos, infertility and more.

Thyroid hormones also pass from mother to fetus, and adequate amounts are necessary for normal growth and brain development of the growing baby (R).

The most common thyroid blood tests done at your GP, and why they aren’t enough

If you have gone to the doctor and your thyroid hormones tested out of range (ie in the ‘red’/ danger zone), you will likely get a prescription to add more hormones (or block their production if you had too many).

A sluggish thyroid usually gets ‘treated’ by a prescription of T4, the precursor hormone. Chances are you know several friends or family members on it, as it is being given out quite frequently. Now one would think, why are they giving out T4, when the active form really is T3? I will get into that in more detail in a future post, but in a nutshell, for many people T4 medication will in fact help normalise thyroid hormone function, as the body will use it to turn it into T3, the active form.

However, there are some where T4 (synthetic thyroxine) does not help improve symptoms, and a combination with T3, the active form, shows better symptom improvement.

Within Functional Medicine we obviously take this even one step further and ask the question of why. ‘Why is the body not producing enough thyroid hormones (or too much) in the first place? What are underlying triggers, such as inflammation from an imbalanced gut microbiome, hidden food intolerances, too much or too little of nutrients needed to make thyroid hormones (such as iodine, selenium, protein), heavy metal toxicity and more that block the conversion?’

I will get into this in more detail another time, today post’s focus is mostly on testing, so let’s get to that (sorry I keep being side tracked, there is just so much info I want to share with you!! ;) ) .

But what if your thyroid hormones are ‘normal’, yet you still don’t feel quite right? Or you feel ok (perhaps a little more fatigued than you’d like to, or finding it a little harder to shift weight), but are wondering if those markers really are optimal, or just OK?

Most likely, you will have received a TSH test. Sometimes, a free T4 test too. Chances are you will not know what your free T3 levels are, as they rarely get tested, nor if there is an autoimmune component to this, as again, they rarely get tested.

I recommend you ask for all of those on your next blood test, or go to a private lab and get them tested if your GP isn’t ‘playing ball’ (and doesn’t see the need to add those tests).

Why simply testing TSH and free T4 is not enough

We used to think that TSH, the thyroid stimulating hormone sent from the brain to the thyroid, is an adequate representation of what is happening with our actual thyroid hormones. That is because when everything works smoothly, TSH levels are tightly regulated by how much thyroid hormones we have floating around the body, via feedback mechanisms. Ie, if enough thyroid hormones are present, the brain downregulates its stimulating action (lowered TSH), and if not enough thyroid hormones are present, it would ramp up the stimulation (increased TSH). We used to also think that each body has a setpoint from birth that decides if we are more prone to be on the low or high end of thyroid levels — for life.

Hence why most often only TSH levels get tested.

However, more recent research indicates that TSH is in fact not enough to represent what is happening with our thyroid hormones, and only adding free T4 to the test panel, which has become more common practise, is still inadequate.

Research suggests that free T3 levels likely can not reliably be predicted by TSH and free T4 levels, and direct measurement of free T3 to be vital to properly assess thryoid health (R).

There is mounting evidence of metabolic and clinical consequences that could be attributed to low serum T3 concentrations in patients treated with levothyroxine (the most commonly prescribed synthetic T4 replacement) despite normal TSH concentrations — including increased bodyweight, slower basal metabolic rate, elevated serum cholesterol concentrations, and statin utilisation (R).

In these cases, simply testing for TSH and free T4 won’t show us the full picture. These tests could be coming back perfectly fine, when in fact free T3 is low.

Why free T3 is so important, in particular if healthy ageing is your goal.

As mentioned earlier, T3 is the actual active thyroid hormone, responsible for most of the thyroid’s actions.

Low T3, even if TSH and free T4 are in normal ranges, has been associated with

• Increased bodyweight
• Slowed metabolism
• Elevated serum cholesterol concentrations (R)
• Increased bodily pain
• Reduced general health, vitality, social functionign and emotional health (R).

What might come as a surprise to some, free T3 has also been linked to longevity.

Increased T3 has been shown to be protective against mortality (R), and lower free T3, even if within the normal reference range, yet on the lower end of it, was associated with all-cause mortality in older adults over 80 years, and this mortality risk increased with a decrease in free T3 in research.

This might be partly due to some of free T3 pro-longevity effects including:

• Increased mitochondrial health and ‘mitophagy’ (removal of damaged mitochondria) (R)
• Increased skeletal muscle mass and strength, and reduced sarcopenia
• Increased physical performance (R)
• Reduced free T3 in combination with inflammation has been associated with an increased risk of martality compared to just inflammation alone or in individuals with higher free T3 levels (R).

And don’t forget about thyroid antibodies

Antibodies are a natural molecule created by our immune system. They help attack invaders such as viruses, and inactive them before they can make us sick. So in theselves, antibodies are great! However, antibodies that re programmed to attack our own body are one of the hallmarks of autoimmune disease, and cause the immune system to attack our own organs. One of these self-antibodies is anti–thyroid peroxidase antibody (TPO-Ab), which is the known cause of autoimmune thyroid disease, most commonly of ‘Hashimoto’s’ (R).

And even without overt thyroid disease such as Hashimoto’s or Grave’s disease, the presence of thyroid auto-antibodies has been shown to predict a higher risk of thyroid disease in future. And even outside of the effects on thyroid function, there is evidence that women with elevated TPOAb and/or TgAb are at increased risk of infertility even if the thyroid hormone level is within a normal range. It has been reported that positive thyroid antibodies could increase the probability of decreased ovarian reserve function, and the decreased ovarian reserve function not only has a negative impact on the fertility of women of childbearing age, but also affects the success rate of in vitro fertilization-embryo transfer pregnancy aid, which may be the reason for the increased risk of infertility caused by positive thyroid antibody (R).

Furthermore, thyroid antibodies have also been shown to contribute to atherosclerosis (= cardiovascular disease) and breast cancer development, likely due to their pro-inflammatory effects (R).

I personally frequently see thyroid antibodies elevated in my practise, and knowing that can allow for the strategy to become more nuanced and tailored to also address autoimmune triggers, rather than simply improving precursors and conversion of thyroid hormones themselves.

OPTIMAL VS SUBOPTIMAL THYROID TEST RANGES

Ok, so you have convinced your doctor to test TSH, free T3 and free T4, and even thyroid antibodies. They all seem fine but you aren’t feeling great?

That is where the differentiation of ‘optimal’ vs ‘suboptimal’ comes into play. As mentioned earlier, for many test results, just because levels are ‘normal’, doesn’t mean they are optimal and cannot already contribute to niggly symptoms now, and if left for too long, to full blown health problems later. This also applies to thyroid results.

‘Normal’ TSH levels should be between 0.35–5.5 (with slight variations, depending on the lab), ‘normal’ free T4 11.9–21.6 pmol/l, normal free T3 3.1–6.8 pmol/l, and normal TPO antibodies < 35 IU/ml.

However, research shows that those markers, for optimal health, should be in much narrower ranges

Why TSH in normal ranges does not necessarily mean it is optimal

Research shows that even while TSH levels A recent study (2022) found that both low- and high-normal TSH levels were associated with increased all-cause and cardiovascular mortality in adults with diabetes (R). All cause mortality, that’s pretty big!

Another study found that in healthy people, the TSH distribution is skewed towards the lower end of the reference range (yet not too low!), with the mean value being around 1.5 uIU/l (R).

In numerous studies, levels above 2.5 (in the ‘high normal range’) were associated with an increased risk for metabolic and cardiovascular concerns, including:

• Increased cortisol levels — with negative downstream effects on our immune system, increased risk of depression, anxiety and poor cognitive function (R)
• Insulin resistance and an increased risk for the development of metabolic syndrome (R)
• An increased risk of atherosclerosis and cardiovascular disorders, via increased inflammation. This was even found in THS levels as low as >2.1 (R)
• Reduced fertility with decreased AMH and skewed ovarian hormones when TSH is higher than 2.5 (R)
• An increased risk for developing overt thyroid disease, with a higher likelihood of existing thyroid auto-antibodies when TSH was above 2.5 (R)
• Worsening of blood pressure and lipid levels (ie cholesterol, etc) (R)
• Increased risk for non-alcoholic fatty liver disease
• Weight gain

However, contrary to what some advocate, lower TSH levels aren’t all better, and ideally we keep them in a narrow, ‘middle’ optimal range.

TSH in the low normal range has been linked to

• Increased risk of heart palpitations
• Adverse bone density, including osteoporosis and subsequent fractures (R).

Optimal ranges for young and middle aged adults appear to be 0.5- 2.5, or if one wants to be even stricter, 2.1.

Interestingly however, this range moves slightly upwards as one get older, with research indicating that those in 70 and over might want to aim for a TSH of 1.9–2.5 (R).

Different research studies into longevity have shown that TSH that is slightly higher than in young people is in fact linked to better longevity, health and a ‘survival advantage’ in older age. More research needs to be done to confirm the exact reasons, however current thoughts are that the aging heart might be less able to handle as much stimulation, and as such benefits from a slightly ‘calmer’ metabolism (R, R).

Why free T3 and T4 in normal ranges does not necessarily mean it is optimal

A similar thing seems to be going on for free T4. While we might intuitively think that a higher level of T4 might be better, there is in fact a bell sized curve. Research indicates that while low T4 levels aren’t good, high levels aren’t great neither!

Similar to the TSH story just mentioned, higher T4 levels in particular as we get older, have been linked to increased mortality, accelerated aging, decreased lifespan, free radical production and heart issues (R, R).

A study found that free T4 levels in the top quartile of the normal range was linked to a higher incidence of atrial fibrillation, coronary heart disease, heart failure and mortality (R, R).

On the contrary, higher T3 is linked to better health outcomes as we get older. One of the possible reasons suggested could be that as we age, the enzymes needed to convert free T4 into free T3 slow down, and with it T4 increases, while T3 reduces. This might also explain why younger individuals often do better with T4 hormone replacement therapy, while older individuals might struggle to reap the same benefits (R).

In summary: For optimal health, metabolism and longevity, we want free T4 to be in the middle of the normal range, while free T3 is best when at the top end of the normal range.

Optimal ranges free T4:

• In younger individuals: 13.5–19.2 pmol/l
• In aged 70 and over: 13.5–14.8 pmol/l (R)

Optimal ranges free T3:

• 3.8–5.99 pmol/l (R)

Why TPO antibodies in normal ranges do not necessarily mean they are optimal

We briefly touched upon thyroid antibodies earlier, and how their presence can predict thyroid issues in future, but also contribute to other health concerns, such as infertility.

As for the other thyroid markers, what we consider to be ‘normal’ thyroid antibodies might in fact already be contributing to issues. Along those lines, research suggests that anti-TPO in normal, yet on the high end of normal, ranges, triggers low grade inflammation, and with it atherosclerosis (an inflammatory condition of the arteries), even in individuals with normal thyroid hormone levels (R, R).

Research suggests the optimal cutoff points for TPOAb were 18.38 and 14.77 IU/mL for predicting clinical and subclinical hypothyroidism, respectively (R).

Another study even went that far to state that any presence of anti-TPO is linked to an increased risk of atherosclerosis (R).

Mayo Clinic considers values above 9.0 IU/mL to be associated with autoimmune thyroiditis, but elevations are also seen in other autoimmune diseases (R).

Beyond the fixed set point of the hypothalamus-pituitary-thyroid axis

The (outdated) belief was that thyroid hormones have a personal set point. However, newer research indicates that they in fact appear to be variable and highly responsive to environmental factors, including the availability or absence of food, inflammation and clock time. During food deprivation and inflammation, thyroid levels decrease without a concomitant rise in serum TSH, reflecting a deviation from negative feedback regulation in the HPT axis (R).

Aging, decreased renal blood flow, malnutrition, metabolic disorder, and inflammatory cytokines increasing may lead to T3 levels decrease (R).

So while our thyroid levels do have a genetic predisposition, it is our lifestyle that influences their actual levels. I will get into the underlying trigger and root causes of thyroid hormones being below optimal in a different post, stay tuned! I would love to hear from you, please do comment below if you found this to be helpful, and if you have questions for the next post that you would like to have covered!

In Health,

Mirthe