Why is thyroid disorder often misdiagnosed?
Part 2: Identifying triggers that your blood tests won’t reveal
Are you on thyroid medication but still feel no improvement in your symptoms? Chances are your thyroid issue has not been correctly diagnosed. You may be on thyroid hormone replacement to normalize your TSH and T4 levels but what if the root cause of your issue is impaired conversion of T4 to T3? Did your doctor look into a possible auto-immune element?
There are number of factors that can throw your test results off kilter. As we discussed in Part 1 of this series, optimal thyroid health is not always about making thyroid hormones in correct amounts. There are other important steps involved in thyroid metabolism, including conversion of T4 into T3 and ultimately proper utilization of T3 by the cells. Any disruption in these steps could make your thyroid function stop working correctly. Worse yet, some of these discrepancies are hard to catch in the standard blood tests ordered by your doctor to diagnose your issue.
1. Did you check your free T3 levels?
You may have TSH and T4 well within range. But you need to look for whether your free T3 levels are fine or not. This is how it works:
- The thyroid gland mostly produces T4, which needs to be converted to T3.
- T3 is initially bound to Thyroid binding globulin or TBG – a transport protein that carries thyroid hormones to various tissues.
- T3 needs to be cleaved from TBG so that it is available to bind to the thyroid hormone receptors in the cells.
- This is when cells can eventually use T3 for its metabolic requirements.
2. Could there be issue with T4 to T3 conversion?
You are getting treatment for your hypothyroidism (underactive thyroid gland), but do you still continue to feel sick, tired and experience nagging symptoms such as weight gain, difficulty losing weight, depression, foggy mind, low energy levels, muscle aches, high cholesterol levels, hair loss, low sex drive among others? Your doctor may order a blood test, but your TSH and T4 levels appear to be within normal range.
A 2016 research published in the Journal of Clinical Endocrinology and Metabolism found that participants on levothyroxine with normal TSH levels were more often taking antidepressants, statins (drugs that lower cholesterol levels) and beta-blockers (drugs that help lower high blood pressure) than the control group with normal, healthy thyroid function. These individuals were also less active and had more weight. These findings confirm what patients with hypothyroidism on standard levothyroxine treatment keep telling the doctor about their worsening symptoms, including depression, lethargy, high cholesterol levels and brain fog.  This means the symptoms are for real despite having followed the standard treatment.
For most patients, standard treatment for hypothyroidism works very well. This involves taking levothyroxine, which is a synthetic version of T4. In hypothyroidism, the pituitary gland produces more TSH to stimulate the thyroid to make more T4. The levothyroxine therapy is aimed at stabilizing TSH levels. Since your body can effectively convert T4 into T3 with the help of deiodinases, everything else is expected to fall in place once your TSH and T4 levels return to normal.
In most settings, the doctor would adjust the dosage on the basis of your TSH and T4 readings and not by what your symptoms are. But what about patients who continue to feel rundown despite having a normal blood panel?
Chances are your body is not able to effectively covert T4 into T3, which is the active hormone your cells need. In that case your free T3 level would be low. Most conventional doctors are likely to miss the conversion issue, even though their patient is not responding well to thyroid medication. For such patients, checking for free T3 levels would give a better picture. Some experts believe that adding T3 to a levothyroxine regimen may also help resolve persistent hypothyroid symptoms. However, more clinical trials are needed to establish that a combination therapy would indeed benefit such patients.
There are a number of factors that can interrupt the conversion process. Addressing these factors along with checking free T3 and free T4 levels in the blood should be considered as an important strategy in treating hypothyroidism. Key factors that may cause impaired conversion include:
- Liver dysfunction
- High cortisol levels
- Estrogen dominance
- Gut dysbiosis or leaky gut
- Selenium and zinc deficiency
- Medications such as amiodarone and beta blockers
Having optimum levels of free T3 are absolutely important for your overall health, and especially for healthy brain functions. T3 regulates the action of neurotransmitters – such as serotonin, norepinephrine, and GABA – that are closely involved in regulating mood, emotions, memory, anxiety, attention span and energy levels.
3. Is autoimmunity the underlying issue?
The most common cause of hypothyroidism is Hashimoto’s thyroiditis, an autoimmune condition where your immune system makes antibodies that attack the thyroid gland. In fact, 90% of the hypothyroidism cases are caused by Hashimoto’s. Testing for antibodies is the right way to diagnose whether or not you have Hashimoto’s.
Again, autoimmune factors and testing for antibodies is something that is often ignored by conventional doctors. Why does it matter? Assuming you have Hashimoto’s, the antibodies will continue destroying the thyroid tissue and your thyroid gland will not be able to produce adequate amounts of hormones. This means your symptoms get worse and worse. In this case, simply increasing the thyroid medication will not help with the underlying problems. It may help you feel better to some extent but there are other things that need to be taken care of.
Chronic inflammation in the body, triggered by stress, long term illness, hidden infections, unhealthy diet, food allergies and poor gut health, can all trigger the development of autoimmune thyroid disorders. In case you have Hashimoto’s (an autoimmune disorder), one should address all these factors as a part of your overall thyroid managing strategy. The idea is to decrease inflammation that may lead to autoimmune process. You can achieve this by:
- Eliminating foods that promote inflammation (gluten, sugar and processed foods)
- Healing your gut
- Identifying and addressing any hidden infections
- Reducing stress and maintaining your adrenal health
4. Have you checked for Reverse T3 levels?
Did you know your body makes another thyroid hormone called reverse T3 or RT3? Your liver naturally converts some of the T4 into RT3, to eliminate excess of T4 from the circulation. In some situations, this conversion of T4 into RT3 takes prominence and this is when your body makes far too much reverse T3. This usually happens when your body needs to save energy to deal with an immediate stressor at hand or to heal and repair from a trauma or injury.
Any kind of emotional or physiological stress, chronic illness, chronic inflammation, surgery, certain medications like beta blockers or exposure to extreme cold can lead to increased levels of RT3 in the blood. It has been found that high reverse T3 often co-exists with abnormal cortisol levels, celiac disease, low B12 levels and low iron.
What’s wrong with high RT3 levels? Reverse T3 is an inactive hormone and it will bind to the thyroid receptors on the cells, preventing uptake of T3. This will give you symptoms associated with low thyroid functions. In this case, hormone replacement therapy may not be beneficial.
5. Is adrenal stress causing your thyroid trouble?
Sometimes your thyroid gland is working just fine. It is the adrenal fatigue that is the underlying culprit. A number of factors can overload your adrenal glands, be it long-term stress, dealing with a chronic infection, high blood sugar levels, lack of sleep and excessive exercise, to name a few. Adrenal stress is often the cause of low thyroid function.
During stress, your adrenal glands release more cortisol. This impacts the workings of your pituitary gland, which is responsible for keeping an eye on T4 and T3 levels in the bloodstream. Whenever these levels drop below an acceptable limit, the pituitary gland secretes TSH, another hormone that stimulates the thyroid gland to make more hormones. Adrenal stress, by compromising the function of Hypothalamus-Pituitary- Adrenal (HPA) axis, downregulates the production of thyroid hormones – leading to hypothyroidism. This manifests into weight gain, depression, fatigue and low energy levels.
In addition, stress also slows down the conversion of T4 to T3 as your body needs to slow down your rate of metabolism so that it can repair itself. In fact, cortisol increases levels of reverse T3. Chronic stress also wreaks havoc on your blood sugar levels and estrogen levels, both of which impacts your thyroid health in their own ways. In addition, chronic stress leads to leaky gut, which again interferes with your thyroid function in a number of ways too, mostly by causing inflammation, increasing the risk of autoimmune disorder and disrupted conversion of T4 into T3.
If the underlying factor for your hypothyroidism is adrenal stress, you must allow your adrenal gland to heal and repair before it creates additional complications that further knock down your thyroid health.
6. Are your TBG levels too high?
What if you are making sufficient thyroid hormones but your cells are not able to properly use these hormones? This can happen when you have abnormal levels of TBG. As a quick recall, thyroid hormones are not simply dumped into the circulation. They are bound to a protein carrier called TBG. The hormone unbounds from TBG on reaching the cell and becomes free or available to be used by the cells.
What happens when you have excessive TBG levels? There will be low levels of unbound T3 hormone available for use. In this scenario, your TSH and T4 levels will be normal, but T3 will be low. High estrogen levels can trigger the liver to make more TBG, leading to elevated levels. As we discussed in Part 1, a number of factors can lead to estrogen dominance in the body including stress, poor liver functions, birth control pills, hormone replacement therapy and constant exposure to endocrine disruptors in the form of plastics, cosmetics, personal grooming products and pesticides.
7. Are your TBG levels too low? (Thyroid resistance)
What happens when you have low TBG? This means more of free T3 hormone is now available to the cells. In this case, cells develop resistance to this superfluous hormone in circulation, something similar to what happens in insulin resistance. This is called thyroid resistance, when your cells can’t use the available free hormone. In other words, hormones are not getting into the cells. High levels of testosterone, insulin resistance and polycystic ovarian syndrome can result in low TBG.
Reduced activity of T3 receptors can also cause thyroid resistance. Usually hormones bind and interact with receptors on the cells to enter and carry out their specified role. Genetic mutations, unremitting stress, elevated cortisol, environmental toxins and certain nutritional deficiencies (such as zinc, vitamin A and fatty acids) can all adversely impact the activity of T3 receptors, making them unresponsive to the hormone knocking at their door. Excessive build up of thyroid hormone makes cells insensitive to their call, leading to thyroid resistance.
Is thyroid medication the only way to manage your thyroid issues?
Hormone replacement therapy is an important strategy in managing your thyroid disorder. But you just can’t ignore the fact that there are a number of factors that are either working alone or in combination to trigger your thyroid problem. So, what is making your thyroid function erratic in the very first place? What is your specific trigger? You need an integrated approach that takes into account the underlying causes and effectively addresses these with lifestyle and diet modifications.
A holistic approach may not always be entirely effective in treating your thyroid problem, but it will help a lot in improving your symptoms and reducing your dependence on thyroid medication. Mostly, it is achieved by lowering inflammation, reducing stress levels and healing your gut – three most important aspects that benefit your thyroid health in multiple ways.
1. Peterson et al. Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy? The Journal of Clinical Endocrinology and Metabolism. 2016.