The Hypothyroid Series – The Basics and Pitfalls Around Lab Testing

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I wanted to start a series of articles that explore the role of the thyroid and how our systems in the body are reliant on it’s proper functioning. In the future, I will chat about its relationship with fertility, weight gain, low energy and mood, unbalanced hormones, stress (BIG TOPIC!), and diminished mental focus. In this article today, I decided to give you a mini anatomy/physiology/lab lecture on the thyroid gland so you are better able to understand it’s complexity.

Anatomy of the thyroid:

Butterfly shaped gland found in front of your neck, just below the thyroid cartilage (aka Adam’s apple). It is one of the largest endocrine glands and consists of two connected lobes.




The primary function of the thyroid is the production of the hormones T4 and T3.

Thyroid physiology is very complex and there are many steps involved. I do not want to overwhelm you so here is just a basic working foundation on the production and conversion of thyroid hormones. So let’s dive in!

Production: There is a section in your brain called the hypothalamus that releases thyrotropin releasing hormone (TRH). TRH tells the pituitary gland, also found in the brain, to produce thyroid stimulating hormone (TSH), which then tells the thyroid to produce T4 (thyroxine) and T3 (triiodothyronine). These thyroid cells combine iodine and the amino acid tyrosine to make T4 and T3. The thyroid gland produces about 90% T4 and only about 10% T3, however T3 possesses about 4x the hormone “strength” as T4.

Conversion of T4 to T3: Outside the thyroid gland, the thyroid hormones are bound to a protein (thyroid binding globulin) to transport them around the rest of the body. At some point, T4 is converted to the majority of T3 by peripheral conversion from T4 by the enzyme 5’-deiodination. In order for this enzyme to function, selenium is required in adequate amounts. Majority of the conversion takes place in the liver, kidneys, and spleen. Free T3 then gets into the cells to exert its metabolic effect.

Every cell in the body has receptors for your thyroid hormones. They are essential for the functioning of many metabolic processes.

Where can things go WRONG?

As you can see, there are many steps and cofactors required to ensure the proper functioning of the thyroid gland. So why is it that when we see a medical doctor for our hypothyroid symptoms, they only test ONE step of the way!

Imagine 3 women coming in for the same issues: constipation, fatigue, difficulty losing weight, and cold hands and feet. All classic symptoms of hypothyroidism, but what most conventional doctors won’t catch is that all three women could have a different defect in their thyroid physiology.

Standard of care for hypothyroidism is exactly the same for every patient that walks in the door. It is absurd to think that all cases of hypothyroidism share the same cause and require the same treatment. Synthroid (levothyroxine sodium) is the standard treatment given for hypothyroidism. The mechanism of action is that it acts like the endogenous thyroid hormone thyroxine (T4), where in the liver and kidney it is converted to T3, the active metabolite.

Typically a standard panel usually includes TSH (thyroid stimulating hormone) and T4 (thyroxine). The ranges for these markers vary from lab to lab, therefore you could be hypothyroid according to one lab company, but not in another. The lab ranges are not based on what a “healthy range” might be, but based on a bell curve of values obtained from people who come to the labs for testing. And who comes in for lab testing mostly: SICK PEOPLE. Therefore the reference ranges are far too broad to catch minor fluctuations in thyroid physiology.

I mentioned above all the other factors that influence the production of thyroid hormone, yet those are never tested for.

Here are some common thyroid patterns seen that are often overlooked due to the lack of further investigation:

Hypothyroidism caused by pituitary dysfunction

  • What this looks like
    • TSH BELOW (1.8 – 3.0) the functional range, but within the standard range (0.4-4.0)
    • T4 is likely LOW
  • If the pituitary gland is not functioning properly, it doesn’t respond to the low levels of thyroid hormone to tell your thyroid gland to start pumping out more T4 and T3.
  • Specific stressors that cause pituitary dysfunction: elevated cortisol that can in turn be caused by active infection, blood sugar imbalances, chronic stress, pregnancy, hypoglycemia, or insulin resistance.
  • Therefore there may not be anything wrong with the thyroid gland itself but rather the pathway that regulated the output of thyroid hormone.

Hypothyroidism caused by elevated TBG (thyroid binding globulin)

  • What this looks like:
    • TSH and T4 will be NORMAL
    • If tested, T3 will be LOW, and T3 uptake and TBG will be HIGH
  • The function of TBG is to bind to thyroid hormones allowing it to be transported through the blood. Being bound to TBG, makes the thyroid hormones inactive and unavailable to tissues.
  • Therefore, when TBG is high, levels of unbound thyroid hormone will be low, contributing to hypothyroid symptoms.
  • A common cause is high estrogen levels. Excess estrogen must be cleared from the body to see a decrease in TBG levels. It is often associated with birth control pills or estrogen replacement pills/creams.

Hypothyroidism caused by decreased TBG

  • What this looks like:
    • TSH and T4 normal
    • T3 HIGH
    • T3 uptake and TBG LOW
  • This is just the reverse about what was mentioned above. You would think this patient would exhibit hyperthyroid symptoms, but if there is too much thyroid in the blood, cells start to develop a resistance.
  • Most likely cause is high testosterone levels, commonly in women with PCOS and insulin resistance.

Lacking conversion of T4 to T3

  • What this looks like:
    • TSH normal
    • T4 normal/low
    • T3 LOW
  • T3 is the form of thyroid hormone that is most active and exerts the greatest metabolic effect.
  • This is a common pattern that can be caused by certain mineral deficiencies (i.e. selenium – required for the conversion enzyme), elevated cortisol levels and excessive oxidative stress.

 Thyroid Resistance

  • What this looks like:
    • All lab tests NORMAL
  • In this scenario, both the thyroid and pituitary are functioning normally, but the hormones are unable to get into where they need to be. Which causes the hypothyroid symptoms.
  • Currently, there is no accurate test to verify the function of cellular receptors directly.
  • Commonly caused by chronic stress and high cortisol levels. May also exhibit elevated homocysteine levels and genetic factors play a role.

Positive Anti-thyroid Peroxidase Antibody (TPO) – Hashimoto’s

  • What this looks like:
    • TSH normal
    • T4 and T3 Normal/low range
  • This autoimmune condition called Hashimoto’s syndrome is when the cells of your own immune system attack your thyroid gland. It is currently the number one cause of overt hypothyroidism and commonly overlooked since the TPO test is rarely performed.
  • This is a unique type of thyroid illness that involves the immune system as well, still presenting with hypothyroid symptoms.
  • Common causes are being ill with a virus/bacteria, estrogen surges, insulin surges, excessive stress, excessive iodine consumption, high levels of heavy metals, and possibly gluten intolerance.


These scenarios above are only a partial list of the several other patterns that can cause hypothyroid symptoms that don’t show up on standard lab tests. If you are suffering with hypothyroid symptoms and your lab results are normal, remember there is always more to the picture. Even if you are on thyroid medication and not finding much relief, the diagnosis may not have been accurate. The success in treating any illness is an accurate diagnosis so you are able to identify the cause of your symptoms.

Here at Whole Family Health, we dig deeper into your symptoms and offer comprehensive thyroid testing to assess the cause of your hypothyroid symptoms. From there, naturopathic treatment can support the thyroid function accordingly using herbal medicines, dietary changes, nutritional supplementation, detoxification, stress management techniques, and acupuncture.

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