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What Is Cellular Hypothyroidism?

Learn if cellular hypothyroidism or tissue hypothyroidism is behind your thyroid symptoms despite normal thyroid lab values.
What Is Cellular Hypothyroidism?
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Hypothyroidism is the condition in which the thyroid gland does not produce enough thyroid hormones. Hypothyroidism comes with a whole host of symptoms, from those that relate to energy metabolism (such as feeling cold, brain fog, fatigue, and difficulty losing weight) to effects across the metabolism (slow digestion, elevated cholesterol, poor hair growth, and depression). 

However, much less discussed is the issue of tissue hypothyroidism, or hypothyroidism at the cellular level. Tissue hypothyroidism or cellular hypothyroidism is a condition that can leave individuals without the energy they need to thrive on a day-to-day basis and the energy they need to respond well to the ever-growing list of protocols they trial. Moreover, it is a compelling consideration for any person who experiences classic hypothyroid symptoms yet is consistently told that their blood results show no evidence of hypothyroidism. 

What is cellular hypothyroidism?

Cellular hypothyroidism has the same symptoms as primary hypothyroidism. However, there are two key differences: thyroid blood levels look normal with cellular metabolism, and cellular hypothyroidism is unlikely to respond well to thyroid hormone replacement medication. There are many occasions where blood levels may even register towards the high end of the range. In some cases, T4 levels even creep above the range. Cellular hypothyroidism is due to poor transport of thyroid hormones into the cells, meaning that blood levels may be misleading.

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What causes cellular hypothyroidism?

Thyroid transport proteins entirely mediate cellular hypothyroidism. So, it is essential to consider what impacts the activity of thyroid transport proteins. A vital consideration here is cellular adenosine triphosphate (ATP), the body's energy currency. 

Adenosine triphosphate (ATP) is the source of energy for use and storage at the cellular level. ATP is often called the "energy currency" of the cell. In addition to providing energy, the breakdown of ATP serves many cell functions like signaling and DNA/RNA synthesis. Most ATP synthesis happens in the mitochondria.

The mitochondria are tiny organelles abundant in each cell (around 500 per cell in most cases). The mitochondria's job is to take the byproducts of carbohydrates and fats, strip them down to their most basic components, and then combust these with oxygen to produce energy that the body can use. Oxidative stress, oxygen availability, and a deficiency of critical nutrients (B vitamins, carnitine, copper, iron, and magnesium) can all affect mitochondrial activity. 

Calorific intake may also be a fundamental issue that has been measured to reduce cellular thyroid transport by up to 50%.

So, not just the mitochondria and cellular energy status influence the thyroid transporters. Another likely interference is elevated fatty acids in the bloodstream, which shut down thyroid transport proteins. These fatty acids can increase whenever there is insulin resistance, which sees fat cells ignore the insulin signal and continuously release fatty acids into the bloodstream. Equally, adrenaline production is also an important consideration. This triggers further release of stored fatty acids to better fuel the body during perceived crises. 

The fermentation products of intestinal bacteria may also cause cellular hypothyroidism. Toxins like indoxyl sulfate or hippuric acid can form when intestinal microbes ferment amino acids and polyphenols. These fermentation products can inhibit the thyroid transport proteins, which means it's helpful to maintain a healthy gut environment that does not allow for fermentation.

Liver and gall bladder problems can also be a cause of cellular hypothyroidism. Liver conditions or bile duct obstruction can raise bilirubin levels. This yellowish pigment is made during the normal breakdown of red blood cells. Bilirubin may also inhibit the transport of thyroid hormone thyroxine (T(4) into the liver.

Kidneys filter out indoxyl sulfate, hippuric acid, and a fatty acid metabolite called CMPF, another metabolite that can cause thyroid transport problems. Consequently, good kidney function remains highly protective against cellular hypothyroidism. This reason is also why individuals with chronic kidney disease often suffer from cellular hypothyroid issues.

How to test for cellular hypothyroidism

The most exact test for cellular hypothyroidism is to test for genetic expression of the thyroid transporters. Researchers currently use this testing method, but it is not available commercially. 

Instead, other options are open to functional practitioners to help understand if cellular hypothyroidism is the cause of your thyroid symptoms. 

The Organic Acid Test (OAT) measures the levels of organic compounds in urine produced in the body as a part of many vital biochemical pathways.

One such compound is malic acid. Malic acid levels are easily measured on an Organic Acids Test. Higher levels of malic acid in the urine may indicate inefficiencies in energy production. Malic acid is processed by an enzyme called malic acid dehydrogenase, activated by thyroid hormones.

Of course, what you do with the information from an Organics Acid Test is just as important to resolve your root cause and symptoms of cellular hypothyroidism. An assessment of contributing factors is equally vital. 

Mitochondrial activity can be measured using a range of highly advanced tests. 

Note: In my experience, there is rarely a need to do any tests beyond the Organic Acids Test.

The Organic Acids Test provides 75 markers relating to various areas of metabolism. Most importantly, this test measures key metabolites that tell us how steps in the energy production pathways are working, allowing us to personalize a treatment plan. The Organic Acids Test also indicates fermentation markers that contribute to cellular hypothyroidism. 

A more detailed picture can be drawn using various qPCR stool tests. A full qPCR panel consists of 12 assays to detect gastrointestinal pathogens. Results from this test can help quantify what's happening in the gut and inform a treatment plan. 

Lastly, bilirubin is included in most basic blood panels, including markers that can flag any kidney issues. Testing for additional blood markers like fasting insulin, fasting glucose, lipids, and HbA1c can also be added to give an idea of insulin sensitivity. 

Treatment options for cellular hypothyroidism

There is no one-size-fits-all treatment option when it comes to cellular hypothyroidism. While cellular hypothyroidism is an issue with the downregulation of the thyroid transporter proteins, several contributing factors may vary from one individual to the next, resulting in different treatment strategies. Using the tests listed above helps identify your specific needs and guide treatment recommendations.

For example, suppose you have raised fatty acids and deficits related to energy production and usage. In this instance, treatment might involve tailored mitochondrial support, low-carbohydrate diets, and insulin-sensitizing herbs.

Or perhaps, your test results show elevated cortisol levels and poor stress response. Treatment might involve support for cortisol output/receptor sensitivity, herbal support for serotonin/GABA activity in the neurotransmitter system, sleep, and stress management recommendations.

I recommend you work with a functional medicine provider to determine a customized treatment plan.

A note from the author

Cellular hypothyroidism can affect our performance, symptoms, and overall wellbeing. Cellular hypothyroidism is a downstream consequence of anything involving mitochondrial performance, energy signaling, detoxification, intestinal health, and stress burden. Cellular hypothyroidism may be an answer for those who live with unexplained chronic or systemic issues. Building a complete map of the metabolic factors and using relevant tests help tailor a personalized treatment plan that can profoundly affect wellbeing and daily function. 

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Disclaimer: The information provided in this article is for educational purposes only and is intended to foster a deeper understanding of the topic discussed and the impact on thyroid health. Please note that this condition is not currently treated by our providers. We encourage readers to consult with a qualified healthcare provider for diagnosis and treatment recommendations tailored to their individual health needs.


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Marek Doyle

Functional Nutritional Therapist

Marek Doyle is a functional nutritional therapist who has spent the last 16 years building a model of personalized nutrition based on the data of over 3,000 individual outcomes, 11,000 test results, and extensive use of the scientific literature. Marek offers one-to-one consultations for clients and his Academy training course for practitioners and enthusiasts based in London, England. He holds a Masters of Science degree in Personalized Nutrition.

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