Carolina Holistic Medicine | Functional & Alternative Medicine | Charleston, SC


Reverse T3 and Reverse T3 Dominance


The thyroid gland is located in the lower part of the neck near your Adam’s Apple. It secretes two essential thyroid hormones: triiodothyronine (T3) and thyroxine (T4) which are responsible for regulating cell metabolism in every cell in your body. They promote optimal growth, development, function and maintenance of all body tissues. They are also critical for nervous, skeletal and reproductive tissue as well as regulating body temperature, heart rate, body weight and cholesterol.

In a healthy patient a normal thyroid gland secretes all of the circulating T4 (about 90 to 100mcg daily) and about 20% of the circulating T3. The T4 made by the thyroid gland circulates throughout the body and is converted by the 5-deiodinase enzymes Type 1 & 2 into T3 or via the 5-deiodinase Type 3 enzymes into reverse T3 in roughly equal amounts of T3. Most of the biological activity of thyroid hormones is due to T3. It has a higher affinity for thyroid receptors and is approximately 4 times more potent than T4. Because 80% of serum T3 is derived from T4 in tissues such as the liver and kidney, T4 is considered a pro-hormone. No receptors have ever been identified for T4. Normal physiological production ratio of T4 to T3 is 3.3:1.

Reverse T3 (rT3) is virtually inactive having only 1% the activity of T3 and being a T3 antagonist binds to T3 receptors blocking the action of T3 and thus acting as a metabolic break. Normal metabolism of T4 requires the production of the appropriate ratio, or balance, of T3 to rT3. If the proportion of rT3 dominates then it will antagonize T3 thus producing hypothyroid symptoms despite sufficient circulating levels of T4 and T3. Reverse T3 has the same molecular structure as T3 however its three dimensional arrangement (stereochemistry) of atoms is a mirror image of T3 and thus fits into the receptor upside down without causing a thyroid response and thus preventing or antagonizing the active T3 from binding to the receptor acting as a metabolic break.

Reverse T3 dominance, also known as Wilson’s Syndrome, is a condition that exhibits most hypothyroid symptoms although circulating levels of T3 and T4 are within normal test limits. The metabolism of T4 into rT3 is in excess when compared to T3 therefore it is a T4 metabolism malfunction rather than a straight forward thyroid deficiency. Periods of prolonged stress may cause an increase in cortisol levels as the adrenal glands respond to the stress. The high cortisol levels inhibit the 5-deiodinase enzyme Type 1 and thus the conversion of T4 into T3 thus reducing active T3 levels. The conversion of T4 is then shunted towards the production of the inactive rT3 via the 5-deiodinase enzyme Type 3. This rT3 dominance may persist even after the stress passes and cortisol levels have returned to normal as the rT3:T3 imbalance itself may also inhibit the 5-deiodinase enzyme Type 1 thus perpetuating the production of the inactive rT3 isomer. There is some argument to this last point with some research indicating that the elevated rT3 is only temporary and not a permanent condition and in most healthy people this may well be the case. We have however found that in many patients suffering from a range of hypothyroid symptoms do indeed have prolonged elevated rT3 levels which respond favorably to this treatment. Many medical practitioners do not accept rT3 dominance theory and thus many doctors will refuse to treat this condition despite the fact many suffers have been successfully treated. See below for the evidence in the references.

Other causes of reverse T3 dominance include: leptin resistance, inflammation (NF kappa-B), dieting, nutrient deficiencies such as low iron, selenium, zinc, chromium, Vit B6 and B12, Vit D and iodine, Low testosterone, low human growth hormone, Insulin dependent Diabetes, Pain, Stress, environmental toxins, Free radical load, Hemorrhagic shock, Liver disease, Kidney disease, Severe or systemic illness, severe injury, Surgery, Toxic metal exposure.



In addition to considering T3 levels we also need to consider rT3 because if it is too high it will block the effects of T3 thus producing hypothyroid symptoms. If this is the case the TSH, T4 and T3 tests alone will give a false impression of true thyroid function and therefore you must also measure rT3 in order to diagnose this condition. Ideally the ratio of T3/rT3 multiplied by 100 should be between 1.06 to 2.2 – preferably towards the upper end of this range. If this ratio is at the low end of this range or below then rT3 dominance is present and slow release T3 therapy needs to be initiated once adrenal exhaustion, hypoglycemia, nutritional deficiencies and/or low sex hormone levels have been ruled out and/or treated as they can all inhibit 5-deiodinase Type 1 activity. In addition nutrients such as selenium, zinc, Vit B6, B12 and E, iron and iodine should be supplemented as they are necessary cofactors for this enzyme to function correctly and thus ensure appropriate T3 production.

It is also very important that if elevated levels of cortisol are found (stage 1 adrenal exhaustion) it should be treated first because if it remains elevated it will only continue to inhibit the 5-deiodinase enzyme and thus continue rT3 production reducing the effectiveness of this treatment. Low cortisol levels should also be treated because low cortisol will reduce the number of T3 receptors and also prevent T3 transport within the cell, again impeding improvement while on this treatment. In addition some patients respond poorly to thyroid medication if adrenal fatigue is present. Therefore we recommend you test adrenal function and correct it before commencing this treatment.

In summary you should have the following tested: DHEA, cortisol, TSH, T3, T4 and reverse T3.



It is important that no T4 (thyroxine), including Armour Thyroid, is used for this condition as the T4 portion of it will only be converted into rT3 and perpetuate the viscous cycle. The idea is to use slow release T3 to provide the active thyroid hormone to alleviate hypothyroid symptoms and to rebalance the T3/rT3 ratio without the risk of increasing rT3 production. This will allow rT3 levels to diminish over time and thus for T3 to be able to bind to its receptors and thus be effective. It is critical that rT3 levels are reduced in order to achieve a positive therapeutic outcome.

Adrenals are also addressed to make sure both DHEA and cortisol levels are within the optimal range to ensure they are not affecting conversion. Testosterone and hGH levels may also need adjusting.

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